Engineered extracellular vesicles: A new approach for targeted therapy of tumors and overcoming drug resistance.

Targeted delivery of anti-tumor drugs and overcoming drug resistance in malignant tumor cells remain significant clinical challenges. However, there are only few effective methods to address these issues. Extracellular vesicles (EVs), actively secreted by cells, play a crucial role in intercellular information transmission and cargo transportation. Recent studies have demonstrated that engineered EVs can serve as drug delivery carriers and showed promising application prospects. Nevertheless, there is an urgent need for further improvements in the isolation and purification of EVs, surface modification techniques, drug assembly processes, and precise recognition of tumor cells for targeted drug delivery purposes. In this review, we summarize the applications of engineered EVs in cancer treatment and overcoming drug resistance, and current challenges associated with engineered EVs are also discussed. This review aims to provide new insights and potential directions for utilizing engineered EVs as targeted delivery systems for anti-tumor drugs and overcoming drug resistance in the near future.

Facilitation of behavioral and cortical emergence from isoflurane anesthesia by GABAergic neurons in basal forebrain / 中国药理学与毒理学杂志

OBJECTIVE To reveal the role of the basal forebrain(BF)GABAergic neurons in the regulation of isoflurane anesthesia and to elucidate the underlying neural pathways.METHODS The activity of BF GABAer-gic neurons was monitored during isoflurane anesthesia using a genetically encoded calcium indicator in Vgat-Cre mice of both sexes.The activity of BF GABAer-gic neurons was manipulated by chemogenetic and opto-genetic approaches.Sensitivity,induction time and emer-gence time of isoflurane anesthesia were estimated by righting reflex.The electroencephalogram(EEG)power and burst-suppression were monitored by EEG recording.The effects of activation of GABAergic BF-thalamic reticu-lar nucleus(TRN)pathway on isoflurane anesthesia were investigated with optogenetics.RESULTS The activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia,obviously decreased during the induction of anesthesia and gradually restored during the emergence from anesthesia.Activation of BF GABAergic neurons with chemogenetics and optogenetics promoted behavioral emergence from isoflurane anesthesia,with decreased sensitivity to isoflurane,delayed induction and accelerated emergence from isoflurane anesthesia.Optogenetic activation of BF GABAergic neurons prom-oted cortical activity during isoflurane anesthesia,with decreased EEG delta power and burst suppression ratio during 0.8%and 1.4%isoflurane anesthesia,respectively.Similar to the effects of activating BF GABAergic cell bod-ies,photostimulation of BF GABAergic terminals in the TRN also strongly promoted cortical activation and behav-ioral emergence from isoflurane anesthesia.CONCLU-SION The GABAergic neurons in the BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthe-sia via the BF-TRN pathway.

Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice / 数字中医药（英文）

Objective@#To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). @*Methods@#A total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. @*Results@#Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). @*Conclusion@#Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

Effects of stereoscopic traction on photosynthetic characteristics, yield, and quality of Codonopsis pilosula under organic cultivation / 中国中药杂志

To solve the serious problem of stem and leaf shading in the middle and late stage of traditional flat planting of Codonopsis pilosula, this study analyzed the effects of different stereoscopic traction heights on the photosynthetic characteristics and growth of C. pilosula and explored the optimal traction height to improve the yield and quality of C. pilosula. The experiment designed three stereo-scopic traction heights [H1(60 cm), H2(90 cm), and H3(120 cm)] with natural growth without traction as the control(CK). The results showed that the increase in stereoscopic traction heights broadened the growth space of stems and leaves of C. pilosula, enhanced the ventilation effect, significantly increased the average daily net photosynthetic rate of C. pilosula, promoted the absorption of intercellular CO_2, decreased the transpiration rate, and reduced the evaporation of water. Moreover, it effectively avoided the problem of weakened photosynthesis, maintained the carbon balance of individual plants, and promoted the growth and development of the C. pilosula roots. In terms of the seed yield of C. pilosula, it was ranked as H2>H1>H3>CK. To be specific, H1 increased by 213.41% compared with CK, H2 increased by 282.43% compared with CK, and H3 increased by 133.95% compared with CK. The yield and quality of C. pilosula were the highest in the H3 treatment group, with the fresh yield of 6 858.33 kg·hm~(-2), 50.59% higher than CK, dry yield of 2 398.33 kg·hm~(-2), 76.54% higher than CK, and lobetyolin content of 0.56 mg·g~(-1), 45.22% higher than CK. Therefore, the stereoscopic traction height has a great influence on the photosynthetic characteristics, yield, and quality of C. pilosula. Particularly, the yield and quality of C. pilosula can be optimized and improved in the traction height treatment of H3(120 cm). This planting method is worth popularizing and applying in the cultivated management of C. pilosula.

Expert Consensus on Sepsis Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

To give full play to the therapeutic advantages of traditional Chinese medicine （TCM） in sepsis， clarify the entry point of integrated TCM and western medicine， further standardize the clinical treatment of TCM， develop a recognized and integrated treatment protocol of TCM and western medicine， and improve the clinical efficacy on sepsis，the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis， a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response， improving blood coagulation dysfunction， and relieving organ damage. Furthermore， they proposed the treatment protocol with integrated TCM and western medicine， which is expected to provide references for actual clinical treatment and scientific research.

Predictive value of preoperative abdominal adipose tissue measurement for early recurrence after resection of hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the predictive value of preoperative abdominal adipose tissue measurement for early recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 238 patients with HCC who underwent surgical resection from January 2018 to January 2020 in 2 medical centers in China were collected, including 46 cases in the First Affiliated Hospital of Chongqing Medical University and 192 cases in the First Affiliated Hospital of Army Medical University. There were 207 males and 31 females, aged 51(48,65)years. All patients underwent abdominal computed tomography (CT) and/or magnetic resonance imaging (MRI) before surgery. Observation indicators: (1) measure-ment of abdominal adipose tissue; (2) follow-up; (3) analysis of influencing factors for early recurrence after resection of HCC; (4) prediction of early recurrence after resection of HCC. Follow-up was conducted by outpatient examinations and telephone interview to detect the postoperative survival of patients up to February 2022. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was performed by the t test. Measurement data with skewed distribution was represented by M(range) or M( Q1, Q3), and comparison between groups was performed by the Mann-Whitney U test. Count data were expressed as absolute numbers or percen-tages, and the chi-square test was used for comparison between groups. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was performed using the Logistic regression model advance method. The receiver operating characteristic curve was drawn, and the area under curve was used to evaluate the efficacy. Results:(1) Measure-ment of abdominal adipose tissue. Of the 238 patients, the total abdominal adipose tissue, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue index, visceral adipose tissue index, subcutaneous adipose tissue index were 292(198,355)cm 2, 153(99,194)cm 2, 128(95,154)cm 2, 106(76,130)cm 2/m 2, (57±27)cm 2/m 2, 46(34,58)cm 2/m 2 for 139 patients with early postoperative recur-rence, versus 174(114,251)cm 2, 78(50,110)cm 2, 88(55,127)cm 2, 64(42,91)cm 2/m 2, (30±16)cm 2/m 2, 31(19,46) cm 2/m 2 for 99 patients without early recurrence, respectively, showing significant diffe-rences between them ( Z=?7.39, ?7.87, ?5.03, ?7.25, t=?9.46, Z=?5.00, P<0.05). (2) Follow-up. All the 238 patients were followed up according to the plan. The survival time of 238 patients was 26(8,44)months. The survival time was 11(5,18)months for patients with postoperative early recur-rence, versus 36(32,43)months for patients without early recurrence, respectively. (3) Analysis of influencing factors for early recurrence after resection of HCC. Results of univariate analysis showed that body mass index, total adipose tissue, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue index, visceral adipose tissue index and subcutaneous adipose tissue index were related factors for early recurrence after resection of HCC ( t=?5.88, Z=?7.39, ?7.87, ?5.03, ?7.25, t=?9.46, Z=?5.00, P<0.05). Results of multivariate analysis showed that visceral adipose tissue index was an independent influencing factor for early recurrence after resection of HCC ( odds ratio=1.06, 95% confidence interval as 1.04?1.08, P<0.05). (4) Prediction of early recurrence after resection of HCC. According to the results of multivariate analysis, the receiver operating characteris-tic curve showed that the area under curve of visceral adipose tissue index was 0.80 (95% confidence interval as 0.75?0.86, P<0.05), with the sensitivity and specificity as 75.5% and 71.7%. Conclusions:Visceral adipose tissue index is an independent influencing factor for early recurrence after resection of HCC. The risk of early recurrence increases with the increase of visceral adipose tissue index.

Clinical value of CT-based three-section formula in identification of Siewert types of adeno-carcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the clinical value of computer tomography (CT)-based three-section formula in identification of Siewert types of adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 62 AEG patients who were admitted to two medical centers, including 33 patients from Peking University Cancer Hospital and 29 patients from the First Affiliated Hospital of Amy Medical University, between January 2019 and January 2021 were collected. There were 53 males and 9 females, aged (66±9)years. All patients underwent CT examination to obtain the coronal and axial images and determine the upper and lower edges of the tumor and the esophagogastric junction, which were imported into the formula for Siewert classification. Observation indicators: (1) results of CT examination and pathological examination; (2) consistence of judgements for CT examination between doctors; (3) consistence of judgements between CT examination and patholo-gical examination. Results of pathological examination came from intraoperative surgical observa-tion and postoperative histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and count data were described as absolute numbers or percentages. The consistency coefficient Kappa ( κ) was used to evaluate the consistency of diagnosis between resear-chers. The κ≥0.75 was regarded as excellent consistency, 0.40< κ<0.75 as good consistency, κ ≤0.40 as poor consistency. Wilcoxon rank sum test was used to evaluate the statistical difference between results of the CT-based three-section formula method and the pathological examination. Taking the results of histopathological examination as standard, the sensitivity, specifi-city, accuracy and 95% confidence interval of the CT-based three-section formula method were calculated. Results:(1) Results of CT examination and pathological examination: all the 62 patients underwent CT examination successfully to obtain the coronal and axial images and determine the upper and lower edges of the tumor and the esophagogastric junction, which were used for Siewert classifica-tion. There were 3 cases with AEG of Siewert type Ⅰ, 47 cases with AEG of Siewert type Ⅱ and 12 cases with AEG of Siewert type Ⅲ according to doctor's judgement from the Peking University Cancer Hospital, and there were 3 cases with AEG of Siewert type Ⅰ, 49 cases with AEG of Siewert type Ⅱ and 10 cases with AEG of Siewert type Ⅲ according to doctor's judgement from the First Affiliated Hospital of Amy Medical University, respectively. After arbitration, there were 2 cases with AEG of Siewert type Ⅰ, 48 cases with AEG of Siewert type Ⅱ and 12 cases with AEG of Siewert type Ⅲ determined by the CT based three-section formula. There were 7 cases of stage T1, 10 cases of stage T2, 24 cases of stage T3, 14 of stage T4a and 7 cases of stage T4b of pathological T staging. There were 2 cases with AEG of Siewert type Ⅰ, 48 cases with AEG of Siewert type Ⅱ and 12 cases with AEG of Siewert type Ⅲ determined by pathological examination. (2) Consistence of judgements for CT examination between doctors: the consistency of Siewert classification determined by CT-based three-section formula between 2 doctors was good ( κ=0.74, P<0.001). (3) Consistence of judgements between pathological examination and CT examination: with Siewert classification determined by pathological examination as reference, the accuracy of Siewert classification determined by CT based three-section formula was 90.3%( κ=0.73, P<0.001). The sensitivity and specificity of CT-based three-section formula were 66.7%(95% confidence interval as 20.8%-93.9%) and 100.0%(95% confidence interval as 93.9%-100.0%) for AEG of Siewert type Ⅰ, 97.7%(95% confidence interval as 88.2%-99.6%) and 72.2%(95% confidence interval as 49.1%-87.5%) for AEG of Siewert type Ⅱ, 73.3%(95% confidence interval as 48.0%-89.1%) and 97.9%(95% confidence interval as 88.9%-99.9%) for AEG of Siewert type Ⅲ, respectively. Conclusion:The CT-based three-section formula can be used for identification of Siewert types of AEG, with a high accuracy.

Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with inv(16)/t(16;16)(p13.1;q22) and/or CBFβ-MYH11 / 中国实验血液学杂志

OBJECTIVE@#To summarize the clinical and laboratory characteristics of patients with acute myeloid leukemia (AML) with inv(16)/t(16;16) (p13.1;q22), and to analyze the risk factors affecting the prognosis of the patients.@*METHODS@#AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11+ admitted to the Department of Hematology, The First Affiliated Hospital of Soochow University from January 1, 2008 to October 30, 2019 were retrospective analyzed, the clinical and laboratory indicators, as well as treatment plans and efficacy evaluations of the patients were all recorded. Furthermore, related factors affecting the overall survival (OS) and event-free survival (EFS) of the patients were analyzed.@*RESULTS@#Among 151 AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFβ-MYH11+, the percentage of additional chromosomal abnormalities was about 27.8%, and the most common additional chromosomal abnormality was +22 (33/151, 21.8%), followed by +8 (11/151, 7.3%). There were 112 patients with perfect NGS examination, and the result showed the most common accompanying gene mutations were KIT mutation (34/112, 30.4%) and FLT3 mutation (23/112, 20.5%). Univariate analysis showed that factors affecting EFS included: NE≤0.5×109/L (P=0.006) and combined K-RAS mutation (P=0.002); Factors affecting OS included: Age≥50 years old (P<0.001) and NE≤0.5×109/L (P=0.016). Multivariate analysis showed that NE≤0.5×109/L (P=0.019) was the risk factors affecting OS. The proportion of bone marrow eosinophilia (BME)≥10.00% (P=0.029) was the risk factors affecting EFS.@*CONCLUSION@#The prognosis for those newly diagnosed AML patients who were of advanced age, the high proportion of bone marrow eosinophils, K-RAS mutations, and agranulocytosis is poor. The treatment plans can be adjusted in the early stage to improve the prognosis of such patients.

Two novel blaNDM-1-harbouring transposons on pPrY2001-like plasmids coexisting with a novel cfr-encoding plasmid in food animal source Enterobacteriaceae.

OBJECTIVES: This study reports identification of the carbapenemase-encoding gene from carbapenem-resistant Enterobacterales from food animals. METHODS: A total of 40 bacterial isolates recovered from 475 faecal swabs obtained on one farm were tested for the presence of the blaNDM-1 gene by PCR. Species identification of three blaNDM-1-positive strains was conducted by MALDI-TOF/MS. Antimicrobial susceptibility testing was performed by broth microdilution. Transferability of the blaNDM-1 and cfr genes was determined by filter mating. The genetic environment of blaNDM-1 and cfr was analysed by whole-genome sequencing. RESULTS: Two Proteus mirabilis (JPM24 and YPM35) and one Providencia rettgeri (YPR25) carried blaNDM-1. The blaNDM-1 genes were located on conjugable pPrY2001-like plasmids often reported to carry important antimicrobial resistance genes (ARGs). YPR25 and YPM35 shared two almost identical conjugable plasmids, one carrying blaNDM-1 and the other cfr. The blaNDM-1 gene in YPR25 (same as YPM35) and JPM24 was located in two novel transposons, designated Tn6922 and Tn6923, respectively. Tn6922 and Tn6923 carried 14 and 7 ARGs, respectively, and both contained multiple copies of IS26 in the same direction, with a high degree of similarity. Additionally, cfr was located on a plasmid with an unreported high frequency of conjugative transfer in YPR25 (same as YPM35). CONCLUSION: We identified two novel blaNDM-1-containing transposons (Tn6922 and Tn6923) present on pPrY2001-like plasmids. The pPrY2001-like blaNDM-1 plasmids coexisted with a novel cfr plasmid, and both could transfer at high frequency, highlighting the importance of continuous surveillance of multiresistant Enterobacterales of animal origin that can serve as a reservoir for ARGs.

Identification of a Novel CSNK2A1-PDGFRB Fusion Gene in a Patient with Myeloid Neoplasm with Eosinophilia / Journal of the Korean Cancer Association, 대한암학회지

Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.

Novel sternoclavicular hook-plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint / 中国骨伤

OBJECTIVE@#To explore the efficacy of a novel sternoclavicular hook-plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint.@*METHODS@#Retrospective analysis of 13 cases of proximal clavicle fracture with dislocation of sternoclavicular joint treated with sternoclavicular hook-plate from June 2011 to January 2019 in our department. There were 9 males and 4 females, aged 26 to 78 years old, with an average age of (54.08±13.91) years old. All the patients had closed injuries without damage of blood vessels and nerves. The patient's operation time, intraoperative blood loss, hospital stay time, and postoperative complications were recorded. Fracture healing and reduction were evaluated according to X-ray and CT after operation. Constant-Murley score and Rockwood sternoclavicular joint score were used to evaluate limb function at 12 months after operation.@*RESULTS@#All the patients were treated with sternoclavicular hook-plate. The operation time ranged from 50 to 76 min, with a mean of (54.08±13.91) min. The intraoperative blood loss ranged from 20 to 56 ml, with a mean of (46.08±11.15) ml. The hospital stay time ranged from 6 to 14 d, with a mean of (8.31±2.32) d. X-ray and CT examination on the second day after operation showed that all fractures and dislocations were anatomically reduced, and shoulder joint function exercise was performed early. All patients were followed up, and the duration ranged from 12 to 24 months, with a mean of (16.77±4.63) months. The healing time ranged from 9 to 13 d, with a mean of (11.00±1.75) d;and the bone healing time ranged from 3 to 4 months, with a mean of (3.65±0.46) months. There were no complications such as infection, internal fixation failure and nerve injury. At 12 months follow-up, the constant Murley score ranged from 78 to 100, with a mean of 87.83± 11.26; and Rockwood score ranged from 9 to 15, with a mean of 13.70±1.85. Among them, 11 cases were excellent, 1 case was good, and 1 case was general.@*CONCLUSION@#The use of the novel sternoclavicular hook-plate for treatment of proximal clavicle fracture with dislocation of sternoclavicular joint is an effectively internal fixation with high safety, allowing early functional exercise for patients.

Clinical value of gadolinium ethoxybenzyl diethylanetriaminepentaacetic acid enhanced MRI in the preoperative diagnosis of macrotrabecular-massive hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the clinical value of gadolinium ethoxybenzyl diethy-lanetriaminepentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) in the preoperative diagnosis of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC).Methods:The diagnostic test was conducted. The clinicopathological data of 150 HCC patients who were admitted to the First Affiliated Hospital of Army Medical University from January 2019 to December 2020 were collected. There were 116 males and 34 females, aged (53±10)years. There were 38 MTM-HCC patients and 112 non-macrotrabecular-massive hepatocellular carcinoma (nMTM-HCC) patients. All patients received Gd-EOB-DTPA enhanced MRI examination. Observation indicators: (1) clinicopathological features of MTM-HCC and nMTM-HCC; (2) imaging features of MTM-HCC and nMTM-HCC; (3) imaging features for diagnosis of MTM-HCC. The normality test of continuous data was analyzed by the Kolmogorov-Smirnov test. Measurement data with normal distribution and homoscedasticity were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M( P25, P75), and comparison between groups was analyzed using Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. The receiver operating characteristic (ROC) curve was used to evaluate diagnostic value of indicators, and Delong test was used for comparison. Results:(1) Clinicopathological features of MTM-HCC and nMTM-HCC: the alpha-fetoprotein and cases with microvascular invasion were 329 μg/L(20 μg/L,1 034 μg/L) and 24 for MTM-HCC patients, versus 25 μg/L(8 μg/L,200 μg/L) and 31 for nMTM-HCC patients, showing significant differences between the two groups ( Z=-3.306, χ2=15.380, P<0.05). (2) Imaging features of MTM-HCC and nMTM-HCC: cases with regular morphology of tumor, intra-tumoral fat, arterial phase peritumoral enhancement, complete capsule, intratumoral necrosis or ischemia, peritumoral hypointense at hepatobiliary phase (HBP) were 6, 4, 20, 5, 28, 17 for MTM-HCC patients, versus 44, 40, 21, 43, 26, 11 for nMTM-HCC patients, showing significant differences between the two groups ( χ2=7.049, 8.684, 16.399, 8.303, 31.368, 22.783, P<0.05). (3) Imaging features for diagnosis of MTM-HCC. ① Results of multivariate analysis showed that intratumoral fat, intratumoral necrosis or ischemia were independent predictors for MTM-HCC ( hazard ratio=4.033,0.215, 95% confidence interval as 1.196-13.603, 0.079-0.588, P<0.05). ② Diagnostic efficacy: the arear under ROC curve, sensitivity and specificity of intratumoral fat combined with intratumoral necrosis or ischemia for diagnosis of MTM-HCC were 0.799(95% confidence interval as 0.718-0.880, P<0.05), 73.7%, 76.8%. The above indicators of intratumoral fat for diagnosis of MTM-HCC were 0.626(95% confidence interval as 0.530-0.721, P<0.05), 89.5%, 35.7%. The above indicators of intratumoral necrosis or ischemia for diagnosis of MTM-HCC were 0.752(95% confidence interval as 0.659-0.845, P<0.05), 73.7%, 76.8%. There were significant differences in the diagnostic efficacy between the intratumoral fat combined with intratumoral necrosis or ischemia and single intratumoral fat, between the intratumoral fat combined with intratumoral necrosis or ischemia and single intratumoral necrosis or ischemia, respectively ( P<0.05). Conclusions:Intratumoral fat, intratumoral necrosis or ischemia on Gd-EOB-DTPA MRI are independent predictors for MTM-HCC. The two combined features has higher diagnostic efficacy. Gd-EOB-DTPA MRI can be used for pre-operative diagnosis of MTM-HCC.

Effect of Safety Bladder Capacity Catheterization on Lower Urinary Tract Function in Patients With Suprasacral Spinal Cord Injury / 中国康复理论与实践

Objective:To evaluate the effect of safety bladder capacity catheterization on lower urinary tract function in patients with supracacral spinal cord injury. Methods:A total of 60 patients with lower urinary tract dysfunction after suprasacral spinal cord injury in our hospital from January to December, 2019 were divided into control group (n = 30) and observation group (n = 30) randomly. Both groups were given intermittent catheterization, the frequency of catheterization was determined according to postvoid residual volume in the control group, while it was according to safety bladder capacity in the observation group. Their maximum destrusor pressure, postvoid residual volume, safety bladder capacity, urinary tract infection and detrusor wall thickness were compared. Results:Eight weeks after intervention, the maximum destrusor pressure and postvoid residual volume decreased, and the safety bladder capacity increased in the observation group (t > 5.623, P < 0.05), and were better than that of the control group (t > 2.242, P < 0.05); the detrusor wall thickness significantly decreased in the observation group (t = 7.871, P < 0.05), and was lower than that of the control group (t = 3.049, P < 0.01). The number of urinary tract infection patients was less in the observation group than in the control group (χ2 = 4.320, P = 0.038). Conclusion:Intermittent catheterization based on safety bladder capacity can improve lower urinary tract function in patients with suprasacral spinal cord injury.

Identification of a Novel CSNK2A1-PDGFRB Fusion Gene in a Patient with Myeloid Neoplasm with Eosinophilia / Journal of the Korean Cancer Association, 대한암학회지

Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.

Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19 / 生物医学与环境科学（英文）

Objective@#The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*Methods@#In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.@*Results@#NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.@*Conclusion@#We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Research progress on long non-coding RNA (lncRNA) in osteoarthritis / 中国骨伤

Osteoarthritis(OA) is a common clinical disease. The incidence of OA increases significantly with age, and the quality of life of patients is seriously affected. In the pathogenesis of OA, cartilage degeneration is the main cause. There are many long non-coding RNA (lncRNA) specifically expressed in osteoarthritis, which is closely related to the occurrence and development of osteoarthritis. Based on the latest research from 2014 to 2019, this paper summarizes the differential expression of lncRNA in osteoarthritis, the mechanism of lncRNA regulating chondrocyte function, and the mechanism of lncRNA regulating cartilage matrix metabolism. The fact that the expression of lncRNA is altered at different stages of OA development indicates that lncRNA can be developed forlife. The biomarkers and therapeutic targets can provide reference for the prevention, treatment and research of osteoarthritis.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study / 中华医学杂志(英文版)

BACKGROUND@#Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.@*METHODS@#We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.@*RESULTS@#At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.@*CONCLUSIONS@#The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.@*TRIAL REGISTRATION@#ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Analgesic effect of combined therapy of medication and acupuncture in PVP for osteoporotic vertebral compression fracture: a randomized controlled trial / 中国针灸

OBJECTIVE@#To evaluate the analgesic effect and application advantage of acupuncture combined with local anesthesia of lidocaine in percutaneous vertebroplasty (PVP) for the patients with osteoporotic vertebral compression fracture (OVCF).@*METHODS@#A total of 60 patients with OVCF and receiving PVP at single vertebra under local anesthesia were selected and randomized into an acupuncture plus medication group and a simple medication group, 30 cases in each one. In the simple medication group, the local laying infiltration anesthesia with 1% lidocaine 30 mL was used. In the acupuncture plus medication group, firstly, filiform needles were used to stimulate Hegu (LI 4), Neiguan (PC 6), Jinmen (BL 63) and Yintang (GV 29) with reducing technique, and then the epidermal infiltration anesthesia was followed with 1% lidocaine 4 mL. The needles were retained till the end of operation. Successively, before operation (T@*RESULTS@#In the acupuncture plus medication group, MAP and HR were lower than those in the simple medication group at T@*CONCLUSION@#Acupuncture combined with medication reduces the dose and adverse reactions of anesthetics, alleviates pain degree of patients, shortens the duration of operation and improves patients' subjective satisfaction in PVP for OVCF.

Effect of Wenjing Huayu Zhitong Therapy in Treating Primary Dysmenorrhea and Its Regulatory Mechanisms on T Cell Subsets / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Wenjing Huayu Zhitong therapy in treating primary dysmenorrhea (PD) with cold coagulation and blood stasis, and to explore its immune mechanisms on PD. Method:The 108 PD patients with cold coagulation and blood stasis syndrome were collected and randomly divided into traditional Chinese medicine (TCM) group, ibuprofen group and placebo group according to the random number table method, with 36 cases in each group. All patients received corresponding medicines three days before menstruation. The patients in TCM group were treated with TCM and ibuprofen sustained release capsule simulator. The patients in ibuprofen group were treated with ibuprofen sustained-release capsule and TCM simulator. The patients in placebo group were treated with TCM simulator and ibuprofen sustained-release capsule simulator. Treatment lasted for 6 consecutive days for three menstrual cycles, and follow-up was conducted for three menstrual cycles after drug withdrawal. The visual analogue score (VAS), total time of abdominal pain and TCM symptom scores in each menstrual cycle were recorded. The levels of CD3+, CD4+, CD8+ and the ratio of CD4+/CD8+ in peripheral blood before and after treatment were detected by flow cytometry. Result:After treatment for three menstrual cycles, both the TCM group and ibuprofen group were better than placebo group in reducing VAS score and reducing total abdominal pain time (P<0.01). The long-term follow-up effect after drug withdrawal in TCM group was significantly better than that in ibuprofen group (P<0.01). The total effective rate was 91.43% (32/35) in TCM group, 66.67% (10/33) in ibuprofen groups, and 30.30% (10/33) in placebo group . The efficacy of the TCM group was better than that of the ibuprofen group (χ2=-2.971, P<0.01), and the efficacy of the ibuprofen group was better than that of the placebo group (χ2=-2.371, P<0.05). After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in TCM group were significantly increased and the levels of CD8+ were decreased significantly as compared with those before treatment (P<0.01). After treatment, the levels of CD4+ and CD4+/CD8+ in TCM group were higher (P<0.05，P<0.01)，while the levels of CD8+ were significantly lower than those in ibuprofen group and placebo group (P<0.01). Conclusion:Wenjing Huayu Zhitong therapy can reduce the VAS score and accumulative time of abdominal pain, and improve the dysmenorrhea symptoms in patients with PD. Reversal of the T cell subsets disorder may be one of its mechanisms in treating PD with cold coagulation and blood stasis.

Middle and Long-term Clinical Effiacacy of Duhuo Jishengtang Combined with Minimally Invasive Decompression of Lumber Spine in Treatment of Degenerative Lumbar Spinal Stenosis with Kidney Deficiency Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Duhuo Jishengtang combined with minimally invasive decompression of lumber spine in the treatment of degenerative lumbar spinal stenosis with kidney deficiency syndrome for more than 3 years. Method:Through a single-center parallel randomized controlled clinical trial， 63 patients with degenerative lumbar spinal stenosis who were hospitalized in Jiangsu Hospital of Traditional Chinese Medicine from October 2015 to April 2017 were observed for more than three years. Among them， there were 31 cases in the operation combined with traditional Chinese medicine group （observation group） and 32 cases in the operation combined with Celebrex and Mecobalamin group （control group）. Both groups were given routine treatment. The observation group was treated with Duhuo Jishengtang for 3 weeks， while the control group was treated with Celebrex and Mecobalamin for 3 weeks. Result:In the aspect of pain improvement， only 3 months after operation， the observation group was superior to the control group （P<0.05）， with no significant advantage at other time nodes during follow-up. During the 3-month follow-up and a longer period， it was confirmed that observation group had a significant advantage in improving lumbar function （P<0.01）. At the last follow-up， the good efficacy rate of observation group was 83.87% （26/31）， while the good efficacy rate of the control group was 62.5% （20/32）. There was no unstable performance in the last follow-up of the two groups. There was no statistically significant difference between two groups. Conclusion:The middle and long-term follow-up for minimally invasive decompression of lumber spine showed a satisfactory efficacy in the treatment of degenerative lumbar spinal stenosis， with no impact on the stability of the operative segments. For patients of lumbar spinal stenosis with kidney deficiency syndrome， Duhuo Jishengtang can promote the recovery of postoperative neurological function， and improve the good efficacy rate of clinical treatment， but with no obvious advantage in pain relieve after operation.