Synthesis of 2'-fucosyllactose from apple pomace-derived xyloglucan oligosaccharides by an α-L-fucosidase from Pedobacter sp. CAU209.

2'-Fucosyllactose (2'-FL) is known for its ability to provide various health benefits to infants, such as gut maturation, pathogen resistance, improved immunity, and nervous system development. However, the production of 2'-FL using α-L-fucosidases is hindered by the lack of low-cost natural fucosyl donors and high-efficiency α-L-fucosidases. In this work, a recombinant xyloglucanase from Rhizomucor miehei (RmXEG12A) was applied to produce xyloglucan-oligosaccharide (XyG-oligos) from apple pomace. Then, an α-L-fucosidase gene (PbFucB) was screened from the genomic DNA of Pedobacter sp. CAU209 and expressed in Escherichia coli. The capability of purified PbFucB to catalyze XyG-oligos and lactose to synthesize 2'-FL was further evaluated. The deduced amino acid sequence of PbFucB shared the highest identity (38.4%) with that of other reported α-L-fucosidases. PbFucB showed the highest activity at pH 5.5 and 35 °C. It catalyzed the hydrolysis of 4-nitrophenyl-α-L-fucopyranoside (pNP-Fuc, 20.3 U mg-1), 2'-FL (8.06 U mg-1), and XyG-oligos (0.43 U mg-1). Furthermore, PbFucB demonstrated a high enzymatic conversion rate in 2'-FL synthesis with pNP-Fuc or apple pomace-derived XyG-oligos as donors and lactose as acceptor. Under the optimized conditions, PbFucB converted 50% of pNP-Fuc or 31% of the L-fucosyl residue in XyG-oligos into 2'-FL. This work elucidated an α-L-fucosidase that mediates the fucosylation of lactose and provided an efficient enzymatic strategy to synthesize 2'-FL either from artificial pNP-Fuc or natural apple pomace-derived XyG-oligos. KEY POINTS: • Xyloglucan-oligosaccharide (XyG-oligos) was produced from apple pomace by a xyloglucanase from Rhizomucor miehei. • An α-L-fucosidase (PbFucB) from Pedobacter sp. CAU209 shared the highest identity (38.4%) with reported α-L-fucosidases. •PbFucB synthesized 2'-FL using apple pomace-derived XyG-oligos and lactose with a conversion ratio of 31%.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Application and design of lymphoma dataset based on real-world research / 中华医学科研管理杂志

Objective:Considering the large amount and poor quality of clinical data, this study aims to explore the establishment of high-quality research database and its role in real-world research by taking the establishment of lymphoma research database as an example.Methods:The expert opinions in the field of lymphoma were collected, and the relevant guidelines and standards were referenced to establish a standard medical knowledge dataset. The electronic diagnosis and treatment data of lymphoma patients treated in Peking University Cancer Hospital from February 2005 to December 2020 were retrospectively extracted, the deep Learning, natural language processing were adopted to build a dynamic intelligent information integration and processing system of " lymphoma database based on electronic medical record system - biological sample information database - extended genetic information database" .Results:The research database not only meets the research needs of clinical researchers, but also realizes the management of traces in the whole process of application, approval, traceability and analysis of hospital medical record data and biological sample data. The total number of research variables in the database was 668, and the structured variables accounted for 46.0%. On December 25, 2021, there were 68 687 lymphoma patients in the database, the ratio of male to female patients was 8/9, and the proportion of patients with ≥3 visits accounted for 23.0%. In addition, researchers can superimpose searches in the database according to the target conditions, display the targeted medical records according to research hypothesis, and then establish a research cohort, conducting statistical modeling, and mining data information.Conclusions:By integrating management processes and using new natural language artificial intelligence technology to establish a high-level evidence-based database, it is helpful for the interconnection and resource sharing of hospital information systems, so as to achieve the purpose of providing reliable and detailed data for real-world research.

The value of preoperative inflammatory markers in predicting recurrence of hepatocellular carcinoma after liver transplantation / 中华消化外科杂志

Objective:To investigate the value of aspartate aminotransferase/lymphocyte ratio (ALR), γ-glutamyltranspeptidase/lymphocyte ratio (GLR) and aspartate aminotransferase/alanine aminotransferase ratio (AAR) in predicting the recurrence of hepatocellular carcinoma after liver transplantation.Methods:The retrospective cohort study was conducted. The clinicopathological data of 178 patients with hepatocellular carcinoma who underwent liver transplantation in Tianjin First Central Hospital from July 2014 to June 2018 were collected. There were 156 males and 22 females, aged (54±9)years. All patients received the first time of orthotopic liver transplantation. Observation indicators: (1) follow-up; (2) the predictive value and cutoff value of each index for tumor recur-rence of patients with hepatocellular carcinoma after liver transplantation; (3) analysis of risk factors for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation; (4) cons-truction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curve and the Log-rank test was used for survival analysis. Factors with P<0.05 in univariate analysis were included in multivariate analysis. Univariate analysis and multivariate analysis were performed by COX proportional risk regression model with forward method. The regression coefficient was used to build the prediction model. The receiver operating characteristic curve was drawn, and the area under curve (AUC) was used to evaluate the predictive ability of prediction model. Results:(1) Follow-up. All 178 patients with hepatocellular carcinoma were followed up for 36(range, 1?74)months after liver transplantation. During the follow-up, there were 41 patients died, 61 patients with tumor recurrence and 117 cases without tumor recurrence. The 3-, 5-year overall survival rates and 3-, 5-year tumor recurrence free survival rates of patients after liver transplantation were 72.8%, 69.9% and 57.3%, 52.8%, respectively. (2) The predictive value and cutoff value of each index for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. The AUC of preoperative serum alpha fetoprotein (AFP), tumor diameter, ALR, GLR, neutrophil to lymphocyte ratio, AAR in recipients were 0.76, 0.70, 0.69, 0.65, 0.64, 0.65 (95% confidence interval as 0.68?0.83, 0.61?0.79, 0.61?0.77, 0.57?0.74, 0.56?0.73, 0.56?0.74, P<0.05), and the corresponding best cutoff value of each index were 228.00 μg/L, 5.25 cm, 92.90, 122.40, 3.00, 2.42. (3) Analysis of risk factors for tumor recurrence of patients with hepato-cellular carcinoma after liver transplantation. Results of multivariate analysis showed the preoperative serum AFP >228.88 μg/L, number of tumor as multiple, tumor diameter >5.25 cm, ALR >92.90, AAR >2.42 were indepen-dent risk factors for tumor recurrence of hepatocellular carcinoma after liver transplantation ( hazard ratio=3.13, 1.90, 2.66, 2.40, 2.75, 95% confidence interval as 1.81?5.41, 1.08?3.35, 1.49?4.74, 1.40?4.11, 1.54?4.91, P<0.05). (4) Construction and evaluation of the predictive model for tumor recurrence of patients with hepatocellular carcinoma after liver transplantation. According to the results of multivariate analysis, the preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR were used to construct the predictive model for tumor recurrence of hepatocellular carcinoma after liver transplantation. The AUC, best cutoff value, specificity and sensitivity of the predictive model were 0.83 (95% confidence interval as 0.76?0.89, P<0.05), 5.5, 80.3% and 73.8%. Of the 178 patients, there were 110 patients with low risk of tumor recurrence (scoring as 0?5) and 68 patients with high risk of tumor recurrence (scoring as 6?16) after liver transplantation. The 1-, 3-, 5-year tumor recurrence free survival rates and 1-, 3-, 5-year overall survival rates of patients with high risk of tumor recurrence were 27.7%, 18.2%, 18.2% and 63.7%, 48.9%, 48.9%, respectively. The above indicators of patients with low risk of tumor recurrence were 92.3%, 82.4%, 74.6% and 90.4%, 87.7%, 83.6%, respectively. There were significant differences of the above indicators between patients with high risk of tumor recurrence and low risk of tumor recurrence ( χ2=67.83, 21.95, P<0.05). Conclusions:The preoperative serum AFP, number of tumor, tumor diameter, ALR, AAR are independent influencing factors for tumor recurrence of hepato-cellular carcinoma after liver transplantation. The predictive model constructed based on the above indexes has a good prediction efficiency.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Epidemiological investigation of a school COVID-19 outbreak in Shanghai / 上海预防医学

ObjectiveTo describe a COVID-19 outbreak due to SARS-CoV-2 Omicron variant in a school and provide suggestions for COVID-19 prevention and control. MethodsData on the COVID-19 outbreak in a school in Putuo District of Shanghai were collected from November 14 to December 20， 2022. Epidemiological characteristics， incidence rate of secondary cases and response measures were described and analyzed. ResultsA total of 27 COVID-19 cases were identified infected with SARS-CoV-2 Omicron BA.5.2 variant， including 14 students （51.9%） and 13 family members / teachers living with those students （48.1%）. The first case occurred on November 14， with peak incidence during November 16-18. The median generation interval of the second generation cases was 2 （2，3） days. The index case （case 1， a student） had a clear contact history outside the school， which was found through routine examination in key populations in the school. Immediate management was conducted after the notification. All the second generation cases were exposed students in the same class with case 1， which were identified during the quarantine， whereas the third generation cases were their family members/teachers living with the second generation cases. The incidence rate within the class and school were 36.8% and 3.0%， respectively. No further social transmission was found outside the school. ConclusionEarly detection， multi-sectoral collaboration， prompt control and quarantine measures are effective in containing SARS-CoV-2 transmission. Health promotion， surveillance， ventilation and prophylactic disinfection should be reinforced in schools， office buildings and other gathering places.

Liver graft preservation and functional maintenance accelerate the development of liver transplantation / 器官移植

As an effective treatment for end-stage liver disease, liver transplantation has been widely carried out worldwide and gradually captivated widespread recognition. With the advancement of liver transplantation techniques, the incidence of postoperative complications has been gradually declined, and the short-term and long-term prognosis of recipients have been constantly improved. However, a huge gap has existed between the supply and demand of donor organs, which is a major factors restricting the development of liver transplantation. The amount of liver transplantation operation in China is increasing year by year, the shortage of donor liver is becoming more and more prominent, and marginal donor liver is increasingly used in clinic. In recent years, the selection criteria of donor organs, organ preservation and functional maintenance have been continuously improved. In this article, the application and development trend of different techniques were reviewed from the perspectives of donor liver preservation and functional maintenance, and recent technical development and research results were summarized, aiming to provide reference for further enhancing the survival rate of grafts and recipients and promoting the development of liver transplantation in China.

Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives / 中国中药杂志

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Improvement effects and mechanism of total flavonoids of Bidens pilosa on lipopolysaccharide-induced neuroin-flammation in mice / 中国药房

OBJECTIVE To investigate the effect and mechanism of total flavonoids of Bidens pilosa L. （TFB） on lipopolysaccharide （LPS）-induced neuroinflammation in mice. METHODS Fifty C57BL/6 mice were randomly divided into normal control group， LPS group and TFB low-dose， medium-dose and high-dose groups， with 10 mice in each group. TFB low-dose， medium-dose and high-dose groups were given TFB solution intragastrically at 60， 120 and 240 mg/kg， and the normal control group and LPS group were given corresponding volume of normal saline， once a day， for consecutive 21 d. From the 15th day of administration， except for the normal control group， other groups were given LPS （400 μg/kg） intraperitoneally for 7 consecutive days to establish neuroinflammatory model. Brain tissues were taken under anesthesia 4 h after the final administration. The morphological changes of neuronal cells in mice were observed； the contents of nitric oxide （NO）， tumor necrosis factor α （TNF- α）， interleukin-1β （IL-1β）， IL-6 and IL-10 were measured， and the expressions of inflammatory pathway-related proteins [inducible NO synthase （iNOS）， cyclooxygenase-2 （COX-2）， myeloid differentiation factor 88 （Myd88） and protein kinase C （PKC）] were measured in the brain tissues of mice. RESULTS Compared with the normal control group， the neuronal arrangement in the hippocampal region of the brain tissue of mice in the LPS group was sparsely disorganized， with a large number of neuronal fixations and shrunken nuclei； the contents of TNF-α， IL-1β， IL-6 and NO in the brain tissue were significantly increased， the contents of IL-10 were significantly decreased， and the relative expressions of iNOS， COX-2， Myd88 and PKC proteins were significantly increased （P＜0.05）. Compared with the LPS group， the neuronal pathological changes in the brain tissue of mice in the TFB low-dose， medium-dose and high-dose groups were 202014810） significantly improved， and the changes of the above indices in the brain tissue were significantly reversed （P＜0.05） CONCLUSIONS TFB has an inhibitory effect on E-mail：pangxjun@163.com neuroinflammation， and its mechanism of action may be related to down-regulation of the expressions of inflammatory pathway-related proteins iNOS， COX-2， Myd88 and PKC， and reduction of inflammatory factors release.

Recent progress in the treatment of intractable sialolithiasis / 北京大学学报(医学版)

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.

Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism / 中国中药杂志

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Nirmatrelvir and the Risk of Post-Acute Sequelae of COVID-19

Long Covid - the disease encompassing the post-acute sequelae of SARS-CoV-2 (PASC) --affects millions of people around the world. Prevention of PASC is an urgent public health priority. In this work, we aimed to examine whether treatment with nirmatrelvir in the acute phase of COVID-19 is associated with reduced risk of post-acute sequelae. We used the healthcare databases of the US Department of Veterans Affairs to identify users of the health system who had a SARS-CoV-2 positive test between March 01, 2022 and June 30, 2022, were not hospitalized on the day of the positive test, had at least 1 risk factor for progression to severe COVID-19 illness and survived the first 30 days after SARS-CoV-2 diagnosis. We identify those who were treated with oral nirmatrelvir within 5 days after the positive test (n=9217) and those who received no COVID-19 antiviral or antibody treatment during the acute phase of SARS-CoV-2 infection (control group, n= 47,123). Inverse probability weighted survival models were used to estimate the effect of nirmatrelvir (versus control) on a prespecified panel of 12 post-acute COVID-19 outcomes and reported as hazard ratio (HR) and absolute risk reduction (ARR) in percentage at 90 days. Compared to the control group, treatment with nirmatrelvir was associated with reduced risk of PASC (HR 0.74 95% CI (0.69, 0.81), ARR 2.32 (1.73, 2.91)) including reduced risk of 10 of 12 post-acute sequelae in the cardiovascular system (dysrhythmia and ischemic heart disease), coagulation and hematologic disorders (deep vein thrombosis, and pulmonary embolism), fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. Nirmatrelvir was also associated with reduced risk of post-acute death (HR 0.52 (0.35, 0.77), ARR 0.28 (0.14, 0.41)), and post-acute hospitalization (HR 0.70 (0.61, 0.80), ARR 1.09 (0.72, 1.46)). Nirmatrelvir was associated with reduced risk of PASC in people who were unvaccinated, vaccinated, and boosted, and in people with primary SARS-CoV-2 infection and reinfection. In sum, our results show that in people with SARS-CoV-2 infection who had at least 1 risk factor for progression to severe COVID-19 illness, treatment with nirmatrelvir within 5 days of a positive SARS-CoV-2 test was associated with reduced risk of PASC regardless of vaccination status and history of prior infection. The totality of findings suggests that treatment with nirmatrelvir during the acute phase of COVID-19 reduces the risk of post-acute adverse health outcomes.

Evaluation of genome size and phylogenetic relationships of the Saccharum complex species.

"Saccharum complex" is a hypothetical group of species, which is supposed to be involved in the origin of modern sugarcane, and displays large genomes and complex chromosomal alterations. The utilization of restricted parents in breeding programs of modern cultivated sugarcane has resulted in a genetic blockage, which controlled its improvement because of the limited genetic diversity. The use of wild relatives is an effective way to broaden the genetic composition of cultivated sugarcane. Due to the infrequent characterization of genomes, the potential of wild relatives is diffused in improving the cultivated sugarcane. To characterize the genomes of the wild relatives, the genome size and phylogenetic relationships among eight species, including Saccharum spontaneum, Erianthus arundinaceus, E. fulvus, E. rockii, Narenga porphyrocoma, Miscanthus floridulus, Eulalia quadrinervis, and M. sinensis were evaluated based on flow cytometry, genome surveys, K-mer analysis, chloroplast genome sequencing, and whole-genome SNPs analysis. We observed highly heterozygous genomes of S. spontaneum, E. rockii, and E. arundinaceus and the highly repetitive genome of E. fulvus. The genomes of Eulalia quadrinervis, N. porphyrocoma, M. sinensis, and M. floridulus were highly complex. Phylogenetic results of the two approaches were dissimilar, however, both indicate E. fulvus displayed closer relationships to Miscanthus and Saccharum than other species of Saccharum complex. Eulalia quadrinervis was more closely related to M. floridulus than M. sinensis; E. arundinaceus differ significantly from Miscanthus, Narenga, and Saccharum, but was relatively close to Erianthus. We proved the point of E. rockii and E. fulvus should not be classified as one genus, and E. fulvus should be classified as the Saccharum genus. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03338-5.

Disease profile and plasma neutralizing activity of post-vaccination Omicron BA.1 infection in Tianjin, China: a retrospective study

BackgroundSARS-CoV-2 Omicron variant BA.1 first emerged on the Chinese mainland in January 2022 in Tianjin and caused a large wave of infections. During mass PCR testing, a total of 430 cases infected with Omicron were recorded between January 8 and February 7, 2022, with no new infections detected for the following 16 days. Most patients had been vaccinated with SARS-CoV-2 inactivated vaccines. The disease profile associated with BA.1 infection, especially after vaccination with inactivated vaccines, is unclear. Whether BA.1 breakthrough infection after receiving inactivated vaccine could create a strong enough humoral immunity barrier against Omicron is not yet investigated. MethodsWe collected the clinical information and vaccination history of the 430 COVID-19 patients infected with Omicron BA.1. Re-positive cases and inflammation markers were monitored during the patients convalescence phase. Ordered multiclass logistic regression model was used to identify risk factors for COVID-19 disease severity. Authentic virus neutralization assays against SARS-CoV-2 wildtype, Beta and Omicron BA.1 were conducted to examine the plasma neutralizing titers induced after post-vaccination Omicron BA.1 infection, and were compared to a group of uninfected healthy individuals who were selected to have a matched vaccination profile. FindingsAmong the 430 patients, 316 (73.5%) were adults with a median age of 47 years, and 114 (26.5%) were under-age with a median age of 10 years. Female and male patients account for 55.6% and 44.4%, respectively. Most of the patients presented with mild (47.7%) to moderate diseases (50.2%), with only 2 severe cases (0.5%) and 7 (1.6%) asymptomatic infections. No death was recorded. 341 (79.3%) of the 430 patients received inactivated vaccines (54.3% BBIBP-CorV vs. 45.5% CoronaVac), 49 (11.4%) received adenovirus-vectored vaccines (Ad5-nCoV), 2 (0.5%) received recombinant protein subunit vaccines (ZF2001), and 38 (8.8%) received no vaccination. No vaccination is associated with a substantially higher ICU admission rate among Omicron BA.1 infected patients (2.0% for vaccinated patients vs. 23.7% for unvaccinated patients, P<0.001). Compared with adults, child patients presented with less severe illness (82.5% mild cases for children vs. 35.1% for adults, P<0.001), no ICU admission, fewer comorbidities (3.5% vs. 53.2%, P<0.001), and less chance of turning re-positive on nucleic acid tests (12.3% vs. 22.5%, P=0.019). For adult patients, compared with no prior vaccination, receiving 3 doses of inactivated vaccine was associated with significantly lower risk of severe disease (OR 0.227 [0.065-0.787], P=0.020), less ICU admission (OR 0.023 [0.002-0.214], P=0.001), lower re-positive rate on PCR (OR 0.240 [0.098-0.587], P=0.002), and shorter duration of hospitalization and recovery (OR 0.233 [0.091-0.596], P=0.002). At the beginning of the convalescence phase, patients who had received 3 doses of inactivated vaccine had substantially lower systemic immune-inflammation index (SII) and C-reactive protein than unvaccinated patients, while CD4+/CD8+ ratio, activated Treg cells and Th1/Th2 ratio were higher compared to their 2-dose counterparts, suggesting that receipt of 3 doses of inactivated vaccine could step up inflammation resolution after infection. Plasma neutralization titers against Omicron, Beta, and wildtype significantly increased after breakthrough infection with Omicron. Moderate symptoms were associated with higher plasma neutralization titers than mild symptoms. However, vaccination profiles prior to infection, whether 2 doses versus 3 doses or types of vaccines, had no significant effect on post-infection neutralization titer. Among recipients of 3 doses of CoronaVac, infection with Omicron BA.1 largely increased neutralization titers against Omicron BA.1 (8.7x), Beta (4.5x), and wildtype (2.2x), compared with uninfected healthy individuals who have a matched vaccination profile. InterpretationReceipt of 3-dose inactivated vaccines can substantially reduce the disease severity of Omicron BA.1 infection, with most vaccinated patients presenting with mild to moderate illness. Child patients present with less severe disease than adult patients after infection. Omicron BA.1 convalescents who had received inactivated vaccines showed significantly increased plasma neutralizing antibody titers against Omicron BA.1, Beta, and wildtype SARS-CoV-2 compared with vaccinated healthy individuals. FundingThis research is supported by Changping Laboratory (CPL-1233) and the Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), sponsored by the Ministry of Science and Technology of the Peoples Republic of China. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrevious studies (many of which have not been peer-reviewed) have reported inconsistent findings regarding the effect of inactivated vaccines against the Omicron variant. On Mar 6, 2022, we searched PubMed with the query "(SARS-CoV-2) AND ((Neutralisation) OR (Neutralisation)) AND ((Omicron) OR (BA.1)) AND (inactivated vaccine)", without date or language restrictions. This search identified 18 articles, of which 13 were directly relevant. Notably, the participants in many of these studies have received only one or two doses of inactivated vaccine with heterologous booster vaccination; other studies have a limited number of participants receiving inactivated vaccines. Added value of this studyTo date, this is the first study to report on the protective effect of inactivated vaccines against the severe disease caused by the Omicron variant. We examine and compare the disease profile of adults and children. Furthermore, we estimate the effect of post-vaccination omicron infection on plasma neutralization titers against Omicron and other SARS-COV-2 variants. Specifically, the disease profile of Omicron convalescents who had received two-dose primary series of inactivated vaccines with or without a booster dose prior to infection is compared with unvaccinated patients. We also analyzed the effect of infection on neutralizing activity by comparing vaccinated convalescents with vaccinated healthy individuals with matched vaccination profiles. Implications of all the available evidenceCompared with adults, child patients infected with Omicron tend to present with less severe disease and are less likely to turn re-positive on nucleic acid tests. Receipt of two-dose primary series or three doses of inactivated vaccine is a protective factor against severe disease, ICU admission, re-positive PCR and longer hospitalization. The protection afforded by a booster dose is stronger than two-dose primary series alone. Besides vaccination, infection with Omicron is also a key factor for elevated neutralizing antibody titers, enabling cross-neutralization against Omicron, wildtype (WT) and the Beta variant.

Epidermal growth factor outperforms placebo in the treatment of diabetic foot ulcer: a meta-analysis.

Background: Diabetic foot ulcers (DFUs) are a life-threatening ailment caused by diabetes. Several growth factors, as well as their various combinations, have shown promising effect in aiding diabetic foot ulcer healing. However, contradictory or paradoxical results are often available, and debates about this issue are ongoing. Therefore, a comprehensive meta-analysis was performed to compare the efficacy and safety of epidermal growth factor (EGF) and placebo in healing diabetic foot ulcers. Methods: The database search included relevant English literature from Cochrane Library, PubMed, Google Scholar, Elsevier, and EMBASE that was published between 2009 and 2021. Inclusion criteria included type 1 and 2 diabetic patients with foot wounds focusing on complete healing rate. Exclusion criteria included combined therapy, non-human studies, reviews, and protocols. To assess the quality of each study, biases regarding random sequence generation, allocation concealment, participant and personnel blinding, outcome assessment blinding and incomplete outcome data were thoroughly identified. Results: Eight randomized control trials comprising 620 patients (337 in EGF group, 283 in placebo group), were included in this meta-analysis. EGF achieved a significantly higher complete healing rate than placebo after four weeks of treatment, with relative risk (RR): 3.04 (0.50, 18.44) and heterogeneity (Chi 2 = 6.46, df = 2 (P = 0.04) I 2 = 69 %). Notably, the healing frequency in the placebo group was 17%, whereas the healing frequency in the epidermal growth factor group was 34%. Likewise, after eight weeks of treatment, the relative risk and heterogeneity were RR: 2.59 (1.42, 4.72) and (Chi 2 =7.92, df= 4 (p= 0.09): I 2= 49%), respectively. Moreover, the risk ratio at 12 weeks was RR: 1.01 (0.42, 2.46), and heterogeneity was (Chi 2 =8.55, df= 2 (p= 0.01): I 2= 77%). Conclusions: Our findings indicate that EGF significantly promotes wound healing, and could be recommended as an effective and safe treatment for DFUs.

Willingness to use and uptake of non⁃occupational post-exposure prophylaxis （nPEP） among men who have sex with men （MSM） in Shanghai / 上海预防医学

Objective To evaluate nPEP willingness and uptake among MSM in Shanghai. Methods MSM were recruited through a NGO-based HIV voluntary counseling testing clinic and several virtual communities using snowball sampling. Results A total of 606 MSM were successfully recruited in which 82.8% （502/606） had heard of nPEP and 81.2% （492/606） were willing to use nPEP. MSM who had been diagnosed with sexually transmitted diseases （STD） were more likely to hold willingness in using nPEP. High cost was the most common reason for being unwilling to use nPEP. 9.9% （60/606） had used nPEP in which 51.7% （31/60） had used twice or more， and 50%（30/60） had missed medication in the last nPEP. MSM who were heterosexual or with other sex orientations except for being bisexuality （OR=2.943， 95%CI： 1.057‒8.191）， being receptor in anal intercourse （OR=3.361， 95%CI： 1.552‒7.282）， having 2 or more sexual partners in the last 30 days （OR=2.242， 95%CI： 1.225‒4.105）， having been diagnosed with STI （OR=2.317， 95%CI： 1.223‒4.389）， and using drugs （OR=2.177，95%CI： 1.052‒4.503） were more likely to use nPEP. Conclusion MSM in Shanghai have a relatively high willingness to use and uptake of nPEP. Comprehensive strategies need to be developed on improving adherence and reducing HIV-risk behaviors.

Feasibility of a Clinical-Radiomics Model to Predict the Outcomes of Acute Ischemic Stroke

Objective@#To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. @*Materials and Methods@#Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. @*Results@#Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. @*Conclusion@#The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.

Expression of long non-coding RNA NR_002578, NR_038264 and NR_046252 in peripheral blood mononuclear cells of patients with primary gout and its clinical significance / 中华风湿病学杂志

Objective:To explore the three long non-coding RNA (long non-coding ribonucleic acid, the expression of lncRNA NR_002578, NR_038264 and NR_046252) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout arthritis (GA) and their clinical value.Methods:Peripheral venous blood, clinical data and laboratory data were collected from 60 gout patients (including 30 AG patients in acute stage and 30 IG patients in intermittent stage) and 50 healthy subjects (HC group). Quantitative reverse transcription PCR (RT-qPCR) was used to detect the expression levels of PBMCs of 3 lncRNAs in GA and HC groups, and the differences of 3 lncRNAs expression levels in different groups were compared and the correlation analysis was conducted with clinical indicators. Receiver operating characteristic curve (ROC) was constructed to evaluate the possible efficacy of lncRNAs in gout diagnosis. The measurement data conforming to normal distribution were tested by t test or variance analysis, and non-normal distribution were tested by Mann-Whitney U test or Kruskal-Wallis H test. The comparison among the three groups was conducted by SNK. Results:① The expression of NR_002578 in GA was significantly lower than that in HC [60.2(16.8, 100.1)×10 -3vs 149.5 (92.6, 221.8)×10 -3, Z=-5.75, P<0.001], subgroup analysis showed that the expression of NR_002578 in AG was significantly lower than that in IG and HC [34.3(8.6, 72.8)×10 -3vs 88.3(47.7, 109.6)×10 -3vs 149.5(92.6, 221.8)×10 -3, H=40.12, P<0.001], and lower in IG than that in HC ( P<0.001). The expression of NR_046252 in GA was significantly higher than that in HC [6.5(2.1, 21.5)×10 -3vs 2.1(1.2, 3.5)×10 -3, Z=-4.21, P<0.001]. The expression of NR_046252 in AG and IG were higher than that of the HC group [6.3(2.0, 12.0)×10 -3vs 7.2(2.4, 30.6)×10 -3vs 2.1(1.2, 3.5)×10 -3, H=21.33, P<0.001], but there was no significant difference between the AG and IG group ( P>0.05). ② Spearman correlation analysis showed that NR_002578 expression was negatively correlated with erythrocyte sedimentation rate (ESR) ( r=-0.29, P=0.024)and hypersensitive C-reactive protein (hs-CRP) ( r=-0.35, P=0.006) in gout patients. ③ The areas under ROC curve of NR_002578 and NR_046252 for diagnosing gout were 0.819 and 0.750, respectively. Conclusion:The abnormal expression of NR_002578 and NR_046252 in gout patients suggests that NR_002578 may be involved in the pathogenesis of gout.

Pyruvate Supplementation Can Prevent HIIE-induced Metabolic Acidosis and Increase the Expression of MCT1/MCT4 in Skeletal Muscles of Rats / 中国生物化学与分子生物学报

As one of the causes of exercise-induced fatigue, exercise-induced metabolic acidosis has attracted much attention. The effect of pyruvate supplementation on exercise-induced metabolic acidosis is rarely reported, and its mechanism has not been fully elucidated. Monocarboxylate transporters (MCTs) play an important role in the maintenance of the acid-base balance, but it is not clear whether pyruvate can alleviate acidosis by increasing the expression of MCTs. In this study, pyruvate (616 mg/kg/day) was supplemented to rats for one week, and then acute HIIE was performed. The HIIE protocol comprised 13 repeats of a 60 s sprint session at 110% VO

Effect and mechanism of bromodomain-containing protein 4 inhibitor JQl on formaldehyde solution induced inflammatory pain in mice / 解剖学报

Objective To explore the expression and role of bromodomain-containing protein 4(BRD4) in spinal cord of mice which suffered inflammatory pain induced by formaldelryde solution. Methods Thirty-two ICR mice were randomly divided into normal saline group and formaldehyde injection 5 minutes, 30 minutes and 60 minutes groups, with 8 mice in each group. The expression of BRD4 protein and mRNA in spinal cord of mice in each group were detected by Western blotting (n = 4/group) and Real-time PCR (n = 4/group); 66 mice were randomly divided into formaldelryde injection group, vehicle (DMSO) plus formaldelryde injection group and 6. 25, 12. 5, 25 and 50 mg/kg JQl injection plus formaldelryde solution group, with 11 mice in each group. The effect of BRD4 inhibitor JQl on spontaneous pain in each group was observed (n= 11/group); Immunohistochemistry (n= 3/group), Real-time PCR (n = 4/group) or Western blotting (n= 4/group) were used to detect the effects of 25 mg/kg JQ1 on the expression of c-fos and glutamate receptor 2 (GluR2) in the spinal cord of model mice. Results The result showed that levels of BRD4 protein (P<0. 01) and mRNA in spinal cord increased significantly 30 min and 60 min after formaldehyde solution injection (P<0. 05). The behavioral test showed that both 25 mg/kg and 50 mg/kg JQf administration could reduce the second phase spontaneous pain compared with the solvent (DMSO) group (P < 0 . 05). Furthennore, immunohistochemistry and Real-time PCR result showed that 25 mg/kg JQf injection could significantly reduce positive numbers (P<0. 01) and high mRNA expression of c-fos in mouse spinal cord induced by formaldehyde solution (P < 0 . 05), and the Western blotting result showed that 25 mg/kg JQf administration could significantly reduce the expression of glutamate receptor GluR2 (P < 0. OOf). Conclusion BRD4 may play an important role in the induction of central sensitization of inflammatory pain, and JQf may alleviate inflammatory pain behavior by inhibiting the formation of central sensitization of pain.