Establishment of a humanized ST6GAL1 mouse model for influenza research.

BACKGROUND: This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1. METHODS: Humanized fragments, consisting of the endothelial cell-specific K18 promoter, human ST6GAL1-encoding gene, and luciferase gene, were microinjected into the fertilized eggs of mice. The manipulated embryos were transferred into the oviducts of pseudopregnant female mice. The offspring were identified using PCR. Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation, and in vivo analysis was performed for screening. Expression of the humanized gene was tested by performing immunohistochemical (IHC) analysis. Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed. RESULTS: Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1. Seven mice were identified as carrying copies of the humanized gene, and the in vivo analysis indicated that hST6GAL1 gene expression in positive mice mirrored influenza virus infection characteristics. The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice. Moreover, the hematologic and biochemical parameters of the positive mice were within the normal range. CONCLUSION: A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Analysis of peripheral blood lymphocyte status in low-level-viremia patients with chronic hepatitis B virus infection after nucleos(t)ide analogue treatment / 中华微生物学和免疫学杂志

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Predictive model of fecal or urinary incontinence among older adults in China / 中华老年医学杂志

Objective:To construct and validate a predictive model of fecal/urinary incontinence among older adults in China.Methods:Data was obtained from the Seventh Chinese Longitudinal Healthy Longevity Survey in 2018.In the questionnaire, "Are you able to control your bowel and urine" , was regarded as the main effect indicator.Receiver operating curves(ROC)were used to find the best cut-off values of calf circumference for predicting fecal/urinary incontinence, and univariate Logistic model method was used to explore the potential factors associated with fecal/urinary incontinence among community-living older adults in China.A random sampling method was used to extract 70% of the survey data as the training set, and the remaining 30% of the survey data as the test set.A multivariate Logistic regression analysis was conducted in the training set to build a prediction model that encompassed all predictors, and a nomogram was plotted.Results:Logistic regression analysis showed that age, small calf circumference(male <28.5 cm, female <26.5 cm), inability to walk 1 km continuously, inability to lift 5 kg items, inability to do three consecutive squats, limited daily activities, and a history of urinary system disorders, nervous system disorders, and cerebrovascular disorders were all risk factors for fecal/urinary incontinence for older adults in China.Female, better socioeconomic status, and normal body mass index were protective factors for fecal/urinary incontinence.The Logistic regression model for predicting fecal/urinary incontinence among Chinese older adults was constructed using the above twelve factors.The consistency index(C-index)value of the model was 0.907, indicating that the model had good predictive ability.The area under the ROC curve(AUC)of the overall sample, training set and test set were 0.906(95% CI: 0.896-0.917), 0.907(95 % CI: 0.894-0.921)and 0.910(95% CI: 0.892-0.928), respectively, indicating that the model had high prediction ability and good discrimination. Conclusions:Age, sex, calf circumference, ability to walk 1 km continuously, ability to lift 5 kg items, ability to do three consecutive squats, daily activities, history of urinary system disorders, nervous system disorders and cerebrovascular disorders, socioeconomic status, and body mass index were independent predictors for fecal/urinary incontinence among older adults in China.The nomogram based on the above indicators has a good predictive effect on fecal/urinary incontinence for older adults.

Clinical study of radiation exposure from atrial fibrillation catheter ablation guided by magnetic navigation system and cryoballoon / 中华放射医学与防护杂志

Objective:To identify the method to reduce X-ray exposure during ablation of atrial fibrillation (AF) by comparing the cryoballoon (CRYO) ablation and remote magnetic navigation (RMN) ablation.Methods:A retrospective analysis was conducted on 144 patients undergoing CRYO ablation (CRYO group) and 121 patients undergoing RMN ablation (RMN group) in our hospital. Entrance surface doses at reference points online, exposure time during procedure and outcomes were analyzed for different types of patients.Results:Compared with the RMN group, the procedure time for the CRYO group significantly decreased [(165.0±23.6), (97.8±18.4) min, t=26.05, P<0.001]. However, the entrance surface dose value [(232.3±130.7), (669.0±387.5) mGy, Z=-12.29, P<0.001] and X-ray exposure time [(8.1±3.1), (23.4±6.2) min, t=-24.57, P<0.001] increased significantly for the CRYO group. No significant difference was found between the two groups in the proportion of maintaining sinus rhythm during follow-up of patients (71.9%, 75.7%, P=0.618). Multiple regression analysis showed that obese patients, patients with non-paroxysmal AF and patients with variant pulmonary veins were associated with an increase in entrance surface dose values in the CRYO group ( t=5.47, 2.23, 3.39, P<0.05). The X-ray exposure time for the three types patients above in the CRYO group also increased ( t=2.87, 3.86, 3.25, P<0.05) in the CRYO group. However, only obese patients in the RMN group had an increase in entrance surface dose value ( Z=-4.15, P<0.001) and no increase in exposure time. For the three types of patients above, there was no significant difference in proportion of maintaining sinus rhythm between the CRYO group and the RMN group during follow-up ( P>0.05). Conclusions:Compared with RMN ablation, the radiation exposure of CRYO AF ablation significantly increased, especially in obese patients, patients with non-paroxysmal AF and patients with pulmonary veins variation. The use of RMN for these types of patients may reduce the radiation exposure without affecting the procedure outcomes.

Surgical outcome and safety of peripheral iridectomy plus goniosynechialysis and goniotomy in the treatment of advanced primary angle-closure glaucoma / 中华实验眼科杂志

Objective:To evaluate the preliminary effectiveness and safety of surgical peripheral iridectomy (SPI) combined with goniosynechilysis (GSL) and goniotomy (GT) in the treatment of advanced primary angle-closure glaucoma (PACG).Methods:A multicenter observational case series study was performed.Thirty-five eyes of 27 patients with advanced PACG, who underwent SPI+ GSL+ GT with a follow-up of at least 6 months, were included from August 2021 to January 2022 at Zhongshan Ophthalmic Center, Handan City Eye Hospital, Shijiazhuang People's Hospital, West China Hospital of Sichuan University, and the Third Affiliated Hospital of Chongqing Medical University.The mean follow-up time was 9(7, 10) months.Pre- and post-operative best corrected visual acuity (BCVA) and intraocular pressure (IOP) were measured with an ETDRS chart and a Goldmann applanation tonometer, respectively.The number of anti-glaucoma medications applied before and after surgery was recorded, and the complications after surgery were analyzed.Success rate of surgery was calculated.Complete surgical success was defined as an IOP of 5-18 mmHg (1 mmHg=0.133 kPa) and 20% reduction from baseline without anti-glaucoma medication or reoperation.Qualified success was defined as achieving criterion of complete success under anti-glaucoma medications.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2021KYPJ177). Written informed consent was obtained from each subject.Results:The mean preoperative IOP was (30.83±8.87)mmHg, which was significantly decreased to (15.69±3.70)mmHg at 6 months after the surgery ( t=8.588, P<0.001), with a 44.00% (34.78%, 60.00%) decline of 13.00(8.00, 21.00)mmHg.The median number of anti-glaucoma medications was significantly reduced from 2(0, 3) preoperatively to 0 (0, 1) postoperatively ( Z=-3.659, P<0.001). The mean preoperative and postoperative 6-month BCVA were 0.80(0.63, 1.00) and 0.80(0.60, 1.00), respectively, showing no significant difference ( Z=-0.283, P=0.777). Complete surgical success rate was 62.86%(22/35), and the qualified success rate was 91.43%(32/35). Surgical complications mainly included hyphema (6/35), IOP spike (3/35), and shallow anterior chamber (4/35). There was no vision-threatening complication. Conclusions:SPI+ GSL+ GT is preliminarily effective and safe in the treatment of advanced PACG, which provides a new option for PACG.

Preparation and properties of hydrogels loaded with phage endolysin Lys84 / 生物工程学报

This study investigated the application of poly(N-isopropylacrylamide)-based interpenetrating network temperature-sensitive hydrogels (notation: IPNT) as the delivery vehicle for phage endolysin Lys84 and the potential of drug-loaded hydrogels as antimicrobial materials. Interpenetrating network temperature-sensitive hydrogels were prepared by free radical polymerization of sodium alginate and N-isopropylacrylamide. Drug-loaded hydrogels (IPNT-Lys84) were obtained by dry soaking method with the endolysin Lys84 of Staphylococcus aureus phage. The physical properties of the hydrogels with and without drug loading were characterized by infrared spectroscopy, scanning electron microscopy, and differential scanning calorimetry. The swelling and deswelling of the hydrogels as well as the release of endolysin Lys84 were investigated. Moreover, the antibacterial properties of IPNT-Lys84 hydrogels at different temperatures and concentrations of the drug solution were studied. The results showed that IPNT-Lys84 hydrogel had uniform pores and a low critical solubility temperature (LCST) of 32 ℃. The equilibrium swelling of the hydrogel was 30 g/g, and the water loss rate was 88% upon deswelling. The release rate of endolysin reached more than 70% within 6 h at 37 ℃. The bactericidal rate of IPNT-Lys84 hydrogel was over 99.9%. The research results showed the feasibility of using IPNT to deliver the endolysin Lys84, and IPNT-Lys84 hydrogel might be an effective antimicrobial material against multi-drug resistant Staphylococcus aureus.

Qualitative Study on Research Participants Informed Consent of Research Characteristics in Clinical Trials of Traditional Chinese Medicine / 中国医学伦理学

【 Objective:】 To understand subjects’ experiences and opinions on clinical trials of traditional Chinese medicine (TCM) and the process of informed consent during the process of participating in TCM clinical trials, and to provide reference for obtaining high-quality informed consent in TCM clinical trials. 【Methods:】 Using qualitative research methods, semi-structured individual in-depth interviews were conducted on 6 participants who had previously participated in TCM clinical trials. 【Results:】 Through data analysis, five major themes and several sub-themes were obtained, including the reasons why participants are willing to participate in TCM clinical trials, the concerns about unwillingness to participate, the information that they hope to be informed during the informed consent process, the specific content that they want to know in TCM clinical trials, and the evaluation of understanding and satisfaction with informed consent. 【Conclusion:】 In the process of informed consent in TCM clinical trials, attention should be paid to the explanation of adverse drug reactions of TCM, the reasonable arrangement and clear notification of the time for participants to participate in the trial, emotional humanistic care in the process of informed consent communication, and the value embodiment of subjects and their expectations for acquiring special knowledge of TCM.

Role of TLR2/NF-κB signaling pathway in aluminum-induced inflammatory response in GMI-R1 cells / 中国职业医学

{L-End}Objective To investigate the role and mechanism of Toll-like receptor 2 (TLR2)/nuclear factor-κB(NF-κB) signaling pathway in the inflammatory response induced by aluminum in the rat GMI-R1 microglia cells. {L-End}Methods GMI-R1 cells in logarithmic growth phase were randomly divided into the control group, positive control group, and low-, medium-, and high-dose groups. The cells in the three dose groups were stimulated with maltolol aluminum at concentrations of 100, 200, and 400 μmol/L, respectively. The cells in the positive control group were stimulated with lipopolysaccharide at a mass concentration of 20 mg/L, while the cells in the control group were not treated. The morphological changes of cells were observed, and the cell survival rate was evaluated by CCK-8 method after 24 hours of culture. The secretion levels of tumor necrosis factor-α (TNF-α), interleukin (IL) -12 and IL-4 were detected by enzyme-linked immunosorbent assay. The relative protein expression of TLR2, NF-κB P65, cluster of differentiation (CD) 68 and CD206 of cells was detected by Western blotting, and the expression of CD68 and CD206 of cells was detected by immunofluorescence method. {L-End}Results The results of cell morphology showed that the number of GMI-R1 cells decreased, the number of activated cells increased, the degree of cell cytoplasm filling decreased, and the cell protrusions elongated with the increase of exposure dose, showing a dose-response relationship. The cell viability of the positive control group and the medium- and high-dose groups were significantly lower than those of the control group (all P<0.05). The secretion levels of TNF-α, IL-12 and the relative expression of TLR2 and CD68 proteins increased (all P<0.05) while the secretion level of IL-4 decreased (all P<0.05) in the cells of positive control group compared with the control group. The secretion levels of TNF-α and IL-12 increased (all P<0.05) while the secretion levels of IL-4 decreased in the cells of the three doses groups (all P<0.05), compared with the control group, and all showed a dose-effect relationship. The relative expression of TLR2 protein in the cells of the three doses groups increased (all P<0.05) compared with the control group. The relative expression of NF-κB p65 and CD68 protein in the cells of the medium- and high-dose groups increased (all P<0.05), but the relative expression of CD206 protein decreased (all P<0.05) compared with the control group. The relative expression of TLR2 and NF-κB p65 protein increased (all P<0.05) while the relative expression of CD206 protein decreased (all P<0.05) in cells of the high-dose group, compared with the low- and medium-dose groups. The average fluorescence intensity of CD68 increased (all P<0.05) while the average fluorescence intensity of CD206 decreased in the cells of high-dose group and the positive control group (all P<0.05), compared with the control group. {L-End}Conclusion Aluminum participated in and promoted the inflammatory response of GMI-R1 cells through the TLR2/NF-κB signaling pathway.

Diagnosis and treatment of pediatric cervical bronchogenic cyst / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the clinical characteristics and surgical treatment outcomes of children with cervical bronchogenic cysts. Methods:A retrospective study of 6 pediatric patients with bronchogenic cysts in the neck region treated in our hospital during 2014 to 2020 was performed. All children underwent complete resection of cervical mass under general anesthesia. Results:There were 6 children, aged from 1 to 5 years, with a median of 2.25 years. There were 3 males and 3 females. The lesions were located on the left neck in 3 cases, the midline neck in 2 cases and the right neck in 1 case. The clinical manifestations were painless mass in 5 cases and recurrent neck infection in 1 case. The size of the mass ranged from 2.1 to 7.5 cm. There was no characteristic clinical or imaging features of bronchogenic cysts. Misdiagnosed as lymphangioma in 3 cases, thyroglossal cyst in 2 cases and piriform fistula in 1 case. The follow-up ranged from 1.50 to 7.75 years, with a median of 4.13 years. All 6 children had no recurrence or complications. Conclusion:Although rare, bronchogenic cysts should be considered in the differential diagnosis of cervical cystic masses in children. Surgery is the most effective way to treat cervical bronchogenic cyst, and histopathological examination is the gold standard for diagnosis.

The airway management and treatment of newborns with micrognathia and laryngomalacia / 临床耳鼻咽喉头颈外科杂志

Objective:To explore the perioperative airway management and treatment of newborns with micrognathia and laryngomalacia. Methods:From January to December 2022, a total of 6 newborns with micrognathia and laryngomalacia were included. Preoperative laryngoscopy revealed concomitant laryngomalacia. These micrognathia were diagnosed as Pierre Robin sequences. All patients had grade Ⅱ or higher symptoms of laryngeal obstruction and required oxygen therapy or non-invasive ventilatory support. All patients underwent simultaneous laryngomalacia surgery and mandibular distraction osteogenesis. The shortened aryepiglottic folds were ablated using a low-temperature plasma radiofrequency during the operation. Tracheal intubation was maintained for 3-5 days postoperatively. Polysomnography（PSG） and airway CT examination were performed before and 3 months after the surgery. Results:Among the 6 patients, 4 required oxygen therapy preoperatively and 2 required non-invasiveventilatory support. The mean age of patients was 40 days at surgery. The inferior alveolar nerve bundle was not damaged during the operation, and there were no signs of mandibular branch injury such as facial asymmetry after the surgery. Laryngomalacia presented as mixed type: type Ⅱ+ type Ⅲ. The maximum mandibular distraction distance was 20 mm, the minimum was 12 mm, and the mean was 16 mm. The posterior airway space increased from a preoperative average of 3.5 mm to a postoperative average of 9.5 mm. The AHI decreased from a mean of 5.65 to 0.85, and the lowest oxygen saturation increased from a mean of 78% to 95%. All patients were successfully extubated after the surgery, and symptoms of laryngeal obstruction such as hypoxia and feeding difficulties disappeared. Conclusion:Newborns with micrognathia and laryngomalacia have multi-planar airway obstruction. Simultaneous laryngomalacia surgery and mandibular distraction osteogenesis are safe and feasible, and can effectively alleviate symptoms of laryngeal obstruction such as hypoxia and feeding difficulties, while significantly improving the appearance of micrognathia.

Mesenchymal stem cell-derived apoptotic bodies alleviate alveolar bone destruction by regulating osteoclast differentiation and function / 国际口腔科学杂志·英文版

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.

Genetic testing and clinical analysis of a patient with Dilated cardiomyopathy due to variant of FLNC gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient with Dilated cardiomyopathy.@*METHODS@#A patient admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University in April 2022 was selected as the study subject. Clinical data and family history of the patient was collected. Targeted exome sequencing was carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of the American College of Medical Genetics and Genomics (ACMG).@*RESULTS@#DNA sequencing revealed that the patient has harbored a heterozygous c.5044dupG frameshift variant of the FLNC gene. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The heterozygous c.5044dupG variant of the FLNC gene probably underlay the pathogenesis in this patient, which has provided a basis for the genetic counseling for his family.

Clinical and genetic analysis of a patient with Loeys-Dietz syndrome due to variant of TGFBR2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS).@*METHODS@#A child who had presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing.@*RESULTS@#Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c.1526G>T missense variant of the TGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+PM2_Supporting+ PM6+PP3+PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The TGFBR2 c.1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of the TGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.

Value of endoscopic ultrasonography in the diagnosis of muddy stones of the common bile duct / 临床肝胆病杂志

Objective To investigate whether endoscopic ultrasonography (EUS) can be an alternative method for diagnostic endoscopic retrograde cholangiopancreatography (ERCP) by comparing the ability of EUS versus CT and transabdominal ultrasonography (TUS) in the diagnosis of muddy stones of the common bile duct. Methods A prospective study was conducted for 53 patients suspected of muddy stones of the common bile duct who attended Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2019 to December 2021, and all patients underwent EUS, TUS, and CT before ERCP. With ERCP and endoscopic sphincterotomy (EST) for removing muddy stones of the common bile duct as the gold standard for the diagnosis of muddy stones of the common bile duct, EUS, TUS, and CT were compared in terms of their ability to display the muddy stones of the common bile duct. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results In the 53 patients, EUS, TUS, and CT had a positive rate of 88.68%, 50.94%, and 62.26%, respectively, in detecting muddy stones of the common bile duct. As for the positive results confirmed by EST under ERCP, EUS had a sensitivity of 93.75%, a specificity of 60.00%, and an accuracy of 90.57% in detecting muddy stones of the common bile duct, while TUS had a sensitivity of 56.25%, a specificity of 100.00%, and an accuracy of 60.38% and CT had a sensitivity of 66.67%, a specificity of 80.00%, and an accuracy of 67.92%. There was a significant difference between EUS and CT in the accuracy in detecting muddy stones of the common bile duct ( χ 2 =8.26, P =0.004), and there was also a significant difference in diagnostic accuracy between EUS and TUS ( χ 2 =13.05, P < 0.001). Conclusion EUS is more accurate than TUS and CT in the diagnosis of muddy stones of the common bile duct, and instead of ERCP, EUS is thus recommended for suspected muddy stones of the common bile duct when TUS and CT fail to identify the lesions in clinical practice, so as to make a confirmed diagnosis and reduce related costs and complications.

Practices of integrating the undergraduate and graduate teaching of Biochemistry and Molecular Biology / 生物工程学报

Biochemistry and Molecular Biology are the cornerstone courses of talent training in the field of life science. Taking these course as an example, this study explored reconstructing the knowledge framework, developing teaching cases, sharing teaching resources, innovating teaching means and establishing ideological education patterns. Supported by the scientific research achievements with discipline characteristics and online teaching platform, this research explored and practiced an integrated curriculum reform mode. This mode is guided by scientific research and education, based on the course development, and driven by communication and cooperation. A shared space of "exchange, practice, openness and informatization" was developed to achieve free and independent integration of undergraduate and graduate teaching motivated by learning knowledge, resulting in an effective student training.

Analysis of the pathogenic spectrum and epidemiological characteristics of 520 children with influenza-like illnesses in Tianjin / 中华微生物学和免疫学杂志

Objective:To understand the epidemiological characteristics and pathogenic spectrum of influenza-like illnesses in Tianjin Children′s Hospital from October 2020 to March 2021, and to provide reference for the prevention, control and clinical diagnosis and treatment of influenza-like illnesses.Methods:A total of 520 throat swabs samples were collected from patients with influenza-like illnesses in sentinel hospitals. Thirty respiratory tract pathogens were detected by real-time fluorescence quantitative PCR. The results were statistically analyzed by descriptive epidemiological methods.Results:Among the 520 samples, 239 were positive for 16 respiratory pathogens with a positive rate of 45.96%. The top three pathogens were respiratory syncytial virus (9.62%, 50/520), rhinovirus (9.62%, 50/520) and cytomegalovirus (5.96%, 31/520). The positive rate of respiratory pathogens was 49.67% in males and 40.91% in females and the difference between males and females was statistically significant (χ 2=3.919, P<0.05). There were significant differences in the positive rates among three age groups (χ 2=6.182, P<0.05) with the highest positive rate in the <2 years old group (52.91%, 91/172) and the lowest rate in the >4 years old group (38.10%, 40/105). There were significant differences in the positive rates detected in different months (χ 2=15.358, P<0.05) and the highest detection rate was in December (58.00%, 58/100), followed by those in November (52.50%, 42/80) and January (47.50%, 38/80). The multiple infection rate was 21.76% (52/239) and most of the multiple infections were caused by rhinovirus and other pathogens (48.08%, 25/52). Conclusions:Respiratory syncytial virus, rhinovirus and cytomegalovirus were the predonimant pathogens responsible for influenza-like illnesses in Tianjin Children′s Hospital from October 2020 to March 2021. Multiple infections were common and children under 2 years old were more susceptible. The detection rate of respiratory pathogens varied in different months. It was necessary to strengthen the surveillance and research on those respiratory pathogens in order to provide scientific data for the prevention and control of respiratory diseases in children.

Genetic diagnosis of MN and ABO hemolytic disease of the newborn complicated with pyruvate kinase deficiency: a case report and literature review / 中国输血杂志

【Objective】 To investigate the clinical and genetic characteristics of hemolytic disease of the newborn(HDN) induced by anti-M complicated with pyruvate kinase deficiency (PKD) disease. 【Methods】 The clinical data of a pregnant woman with unexplained adverse pregnancy outcome in the third trimester were retrospectively analyzed, and neonate anemia status and blood transfusion were followed up. With informed consent, peripheral blood of the neonate and her parents were collected for serological tests and disease-related gene target sequence capture and sequencing. The clinical and genetic characteristics of HDN induced by anti-M or PKD were reviewed. 【Results】 The neonate presented severe anemia, hepatosplenomegalism, hyperbilirubinemia at birth, and was confirmed MN combined with ABO neonatal hemolysis by serological tests. The neonate recovered by receiving blood exchange and phototherapy treatments, but he needed to receive blood transfusion each month because of hemolytic anemia. Genetic analysis showed that the neonate had compound heterozygous mutations (c. 1096C>T; c. 941T>C) of PKLR gene inherited from her parents. 【Conclusion】 The clinical manifestations of PKD are similar to that of HDN caused by anti-M in the early stage of the disease. Clinicians should exclude the metabolic diseases of red blood cells when diagnosing severe HDN caused by anti-M.

Establishment of the maximum surgical blood order schedule for cesarean sections / 中国输血杂志

【Objective】 To establish the catalog of maximum surgical blood order schedule(MSBOS) for cesarean sections with different obstetric complications, so as to guide the doctors of clinical and Blood Transfusion Department to prepare blood reasonably. 【Methods】 The blood transfusion data during cesarean sections from January to October 2021 in our hospital were collected via medical record information system and blood bank system.The blood recipients were classified according to the main obstetric complications. The incidence of blood transfusion, per capita RBC transfusion units, blood transfusion index (TI) and other indicators were calculated, the literature and the risk of massive hemorrhage were referred, and the actual situation of Obstetrics Department was considered to formulate the obstetric MSBOS of our own. 【Results】 1) The blood recipients during cesarean sections were mainly diagnosed as placental abruption, placental implantation, central placenta previa and severe preeclampsia; the incidence of blood transfusion of them was 17.9%(20/112), 17.7%(15/85), 16.8% (27/161)and 5.2%(9/173), respectively, and TI indexes was 0.9, 1.3, 1.0 and 0.3, respectively. 2) The MSBOS of Obstetrics Department in our hospital had been established, and the blood preparation for obstetric surgery was divided into three categories: T(blood typing)/S(antibody screening), T(blood typing)/S(antibody screening)/C(crossmatch) 2 U, and T/S/C 4 U. 【Conclusion】 The establishment of MSBOS in Obstetrics Department of our hospital provides references for preparing blood reasonably.

Research progress on pathogenesis of skin graft-versus-host disease / 器官移植

Graft-versus-host disease (GVHD) is a major cause that prevents widespread application of allogeneic hematopoietic stem cell transplantation. GVHD is a complication that can affect all systems of the body, such as skin, liver, lung and gastrointestinal tract, among which skin is the most vulnerable organ. At present, the pathogenesis of skin GVHD has not been fully elucidated, and no effective treatment has been established. Severe or extensive chronic GVHD significantly affects the quality of life of the recipients. Consequently, it is urgent to unravel the pathogenesis of skin GVHD and explore novel therapeutic treatment. Cytokines, such as interleukin (IL)-22, IL-17, IL-6 and interferon (IFN)-γ, have been proven to play pivotal roles in the progression of skin GVHD. Nevertheless, the specific mechanism remains elusive. In this article, research progresses at home and abroad on the mechanism underlying the roles of these cytokines in skin GVHD were reviewed, aiming to provide novel ideas for the prevention and treatment of skin GVHD.