Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome / 亚洲男科学杂志(英文版)

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Research Progress of Metabolomics Techniques Combined with Machine Learning Algorithm in Wound Age Estimation / 法医学杂志

Wound age estimation is the core content in the practice of forensic medicine. Accurate estimation of wound age is a scientific question that needs to be urgently solved by forensic scientists at home and abroad. Metabolomics techniques can effectively detect endogenous metabolites produced by internal or external stimulating factors and describe the dynamic changes of metabolites in vivo. It has the advantages of strong operability, high detection efficiency and accurate quantitative results. Machine learning algorithm has special advantages in processing high-dimensional data sets, which can effectively mine biological information and truly reflect the physiological, disease or injury state of the body. It is a new technical means for efficiently processing high-throughput big data. This paper reviews the status and advantages of metabolomic techniques combined with machine learning algorithm in the research of wound age estimation, and provides new ideas for this research.

Research progress of functional alignment robot assisted knee replacement / 中国骨伤

The correct alignment of the knee joint is considered to be one of the most influential factors in determining the long-term prognosis after total knee arthroplasty(TKA). In order to achieve the correct alignment goal, many different alignment concepts and surgical techniques have been established. For example, mechanical alignment(MA), kinematic alignment(KA) and functional alignment(FA) have their own characteristics. MA focuses on achieving neutral alignment of the limbs, parallel and equal bone gaps during stretching and flexion. KA aims to restore the patient 's natural joint line, make the joint level and angle normal and improve the physiological soft tissue balance, and strive to reproduce the normal knee function;among them, functional alignment(FA) developed with robot-assisted surgery technology is a relatively new alignment concept. It not only considers the alignment of the body, but also aims to achieve flexion and extension balance, while respecting the native soft tissue capsule. It not only restores the plane and slope of the in situ joint line accurately during the operation, but also takes into account the balance of soft tissue, which is a better alignment method. Therefore, it is of great significance to correctly construct the lower limb force line of patients, which is helpful to restore knee joint function, relieve pain symptoms and prolong the service life of prosthesi. However, compared with traditional TKA, the operation time of robot-assisted FA-TKA is prolonged, which means that the probability of postoperative infection will be greater. At present, most studies of FA technology report short-term results, and the long-term efficacy of patients is not clear. Therefore, long-term research results are needed to support the application of this technology. Therefore, the author makes a review on the research status of functional alignment.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation / 亚洲男科学杂志(英文版)

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Prediction of EGFR mutant subtypes in patients with non-small cell lung cancer by pre-treatment CT radiomics and machine learning / 中华放射医学与防护杂志

Objective:To evaluate the feasibility and clinical value of pre-treatment non-enhanced chest CT radiomics features and machine learning algorithm to predict the mutation status and subtype (19Del/21L858R) of epidermal growth factor receptor (EGFR) for patients with non-small cell lung cancer (NSCLC).Methods:This retrospective study enrolled 280 NSCLC patients from first and second affiliated hospital of University of South China who were confirmed by biopsy pathology, gene examination, and have pre-treatment non-enhanced CT scans. There are 136 patients were confirmed EGFR mutation. Primary lung gross tumor volume was contoured by two experienced radiologists and oncologists, and 851 radiomics features were subsequently extracted. Then, spearman correlation analysis and RELIEFF algorithm were used to screen predictive features. The two hospitals were training and validation cohort, respectively. Clinical-radiomics model was constructed using selected radiomics and clinical features, and compared with models built by radiomics features or clinical features respectively. In this study, machine learning models were established using support vector machine (SVM) and a sequential modeling procedure to predict the mutation status and subtype of EGFR. The area under receiver operating curve (AUC-ROC) was employed to evaluate the performances of established models.Results:After feature selection, 21 radiomics features were found to be efffective in predicting EGFR mutation status and subtype and were used to establish radiomics models. Three types models were established, including clinical model, radiomics model, and clinical-radiomics model. The clinical-radiomics model showed the best predictive efficacy, AUCs of predicting EGFR mutation status for training dataset and validation dataset were 0.956 (95% CI: 0.952-1.000) and 0.961 (95% CI: 0.924-0.998), respectively. The AUCs of predicting 19Del/L858R mutation subtype for training dataset and validation dataset were 0.926 (95% CI: 0.893-0.959), 0.938 (95% CI: 0.876-1.000), respectively. Conclusions:The constructed sequential models based on integration of CT radiomics, clinical features and machine learning can accurately predict the mutation status and subtype of EGFR.

Association of the occurrence of reticular macular diseases with chronic kidney disease based on estimated glomerular filtration rate / 中华实验眼科杂志

Objective:To analyze the relationship between reticular macular disease (RMD) and chronic kidney disease (CKD) by estimated glomerular filtration rate (eGFR).Methods:A cross-sectional study was conducted.Thirty-six consecutive patients (71 eyes) with subretinal drusenoid deposits in at least one eye in optical coherence tomography (OCT) images were enrolled as the RMD group, and 29 consecutive patients (50 eyes) with age-related macular degeneration (AMD) in at least one eye were identified as the non-RMD group at the First Affiliated Hospital of Guangzhou Medical University from February to September 2019.In the same period, 32 healthy volunteers (64 eyes) without eye disease were included as the healthy control group.Serum was collected to calculate the estimated creatinine clearance (eCcr) and the eGFR.The choroidal thickness of macular fovea and the flow density of choroidal capillary layer were measured by OCT.The related factors of RMD and the correlation between CKD and RMD were analyzed by multiple logistic regression analysis.The relationship between eGFR and choroidal capillary blood flow density and foveal choroidal thickness in RMD patients was analyzed by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No.2022-50)Results:The eGFR value of the RMD group was (66.40±27.58)ml/(min·1.73 m 2), which was significantly lower than (84.40±20.91)ml/(min·1.73 m 2) of the non-RMD group and (87.64±22.32)ml/(min·1.73 m 2) of the healthy control group (both at P<0.01). eGFR was significantly correlated with the occurrence of RMD ([odds ratio, OR]=0.973, 95%[confidence interval, CI]: 0.954-0.992, P=0.005). Subgroup analysis showed that this correlation was significant in the CKD stage (eGFR<60 ml/[min·1.73 m 2]) ( OR=6.482, 95% CI: 1.543-27.236, P=0.011). The choroidal thickness of the macular fovea in the RMD group was significantly lower than that of the non-RMD grup and healthy control group (both at P<0.01). In the RMD group, no significant correlation was found between the choroidal thickness of the macular fovea and eGFR ( r=0.138, P>0.05), and the flow density of choroidal capillary layer was moderately positively correlated with eGFR ( r=0.457, P<0.05). Conclusions:There is a correlation between the occurrence of CKD and RMD, which may be due to the confounding effect of the systemic microcirculation disorder.

Surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multi-disciplinary diagnosis and treatment / 中华消化外科杂志

Objective:To investigate the surgical efficacy and prognosis influencing factors of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment.Methods:The retrospective cohort study was conducted. The clinicopathological data of 91 patients with hilar cholangiocarcinoma who underwent surgery in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from April 2004 to April 2021 were collected. There were 59 males and 32 females, aged (61±10)years. Patients who were admitted from April 2004 to March 2014 underwent traditional surgical diagnosis and treatment, and patients who were admitted from April 2014 to April 2021 underwent multidisciplinary diagnosis and treatment. Observation indica-tors: (1) surgical situations; (2) postoperative situations; (3) postoperative pathological examina-tions; (4) postoperative prognosis analysis; (5) influencing factors of postoperative prognosis. Follow-up was conducted using telephone interview and outpatient examination. Patients were followed up once every 6 months after surgery to detect survival. The follow-up was up to April 2023. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was conducted using the rank sum test. Count data were described as absolute numbers or percentages, 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 calculate survival rate. The Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard model. Results:(1) Surgical situations. Of the 91 patients, there were 65 cases receiving hemi- or expanded hemi-hepatectomy, 13 cases receiving tri-hepatectomy, 9 cases receiving partial hepatectomy, 4 cases receiving extrahepatic bile duct resection. There were 24 cases receiving combined vein resection and reconstruction, 8 cases receiving combined pancreaticoduodenectomy, 6 cases receiving com-bined hepatic artery resection and reconstruction, including 24 cases receiving extended radical surgery (tri-hepatectomy, hepatic artery resection and reconstruction, hepatopancreaticoduodenec-tomy). The operation time, volume of intraoperative blood loss and intraoperative blood transfusion rate of 91 patients was (590±124)minutes, 800(range, 500?1 200)mL and 75.8%(69/91), respectively. Of the 91 patients, cases receiving extended radical surgery, the volume of intraoperative blood loss were 4, 650(range, 300?1 000)mL in the 31 patients who were admitted from April 2004 to March 2014, versus 20, 875 (range, 500?1 375)mL in the 60 patients who were admitted from April 2014 to April 2021, showing significant differences between them ( χ2=4.39, Z=0.31, P<0.05). (2) Post-operative situations. The postoperative duration of hospital stay and cases with postoperative infectious complications were (27±17)days and 50 in the 91 patients. Cases with abdominal infection, cases with infection of incision, cases with bacteremia and cases with pulmonary infection were 43, 7, 5, 8 in the 91 patients. One patient might have multiple infectious complications. Cases with bile leakage, cases with delayed gastric emptying, cases with chylous leakage, cases with liver failure, cases with pancreatic fistula, cases with intraperitoneal hemorrhage, cases with reoperation, cases dead during the postoperative 90 days were 30, 9, 9, 6, 5, 3, 6, 3 in the 91 patients. Cases with abdominal infection was 10 in the 31 patients who were admitted from April 2004 to March 2014, versus 33 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=4.24, P<0.05). Cases dead during the postoperative 90 days was 3 in the 31 patients who were admitted from April 2004 to March 2014, versus 0 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( P<0.05). (3) Post-operative pathological examinations. Of the 91 patients, cases with Bismuth type as type Ⅰ?Ⅱ, type Ⅲ, type Ⅳ, cases with T staging as Tis stage, T1 stage, T2a?2b stage, T3 stage, T4 stage, cases with N staging as N0 stage, N1 stage, N2 stage, cases with M staging as M0 stage, M1 stage, cases with TNM staging as 0 stage, Ⅰ stage, Ⅱ stage, Ⅲ stage, ⅣA stage, ⅣB stage, cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 46, 30, 1, 9, 25, 30, 26, 49, 36, 6, 85, 6, 1, 7, 13, 58, 6, 6, 63, 28. Cases with R 0 radical resection, cases with R 1 or R 2 resection were 15, 16 in the 31 patients who were admitted from April 2004 to March 2014, versus 48, 12 in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=9.59, P<0.05). (4) Postoperative prognosis analysis. Of the 91 patients, 3 cases who died within 90 days after surgery were excluded, and the 5-year overall survival rate and median overall survival time of the rest of 88 cases were 44.7% and 55 months. The 5-year overall survival rate was 33.5% in the 28 patients who were admitted from April 2004 to March 2014, versus 50.4% in the 60 patients who were admitted from April 2014 to April 2021, showing a significant difference between them ( χ2=5.31, P<0.05). Results of further analysis showed that the corresponding 5-year overall survival rate of cases without lymph node metastasis was 43.8% in the 16 patients who were admitted from April 2004 to March 2014, versus 61.6% in the 31 patients who were admitted from April 2014 to April 2021. There was a significant difference in the 5-year overall survival rate between these patients without lymph node metastasis ( χ2=3.98, P<0.05). The corresponding 5-year overall survival rate of cases with lymph node metastasis was 18.5% in the 12 patients who were admitted from April 2004 to March 2014, versus 37.7% in the 29 patients who were admitted from April 2014 to April 2021. There was no significant difference in the 5-year overall survival rate between these patients with lymph node metastasis ( χ2=2.25, P>0.05). (5) Influencing factors of postoperative prognosis. Results of multivariate analysis showed that poorly differentiated tumor and R 1 or R 2 resection were inde-pendent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma ( hazard ratio=2.62, 2.71, 95% confidence interval as 1.30?5.29, 1.30?5.69, P<0.05). Conclusions:Compared with traditional surgical diagnosis and treatment, treatment of hilar cholangiocarcinoma based on multidisciplinary diagnosis and treatment can expand surgical indications, reduce proportion of dead patients within 90 days after surgery, improve proportation of radical resection and long-term survival rate. Poorly differentiated tumor and R 1 or R 2 resection are independent risk factors influencing prognosis after surgical treatment of hilar cholangiocarcinoma.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Diagnostic value of 18F-prostate specific membrane antigen PET/CT combined with multiparametric-MRI in identifying the grade group of prostate cancer / 中华泌尿外科杂志

Objective:To investigate the diagnostic value of the combination of 18F-prostate specific membrane antigen (PSMA) PET/CT and multiparametric magnetic resonance imaging (mpMRI) in identifying the grade group of prostate cancer, using parameters derived from the two imaging modalities. Method:Prostate cancer patients diagnosed by histopathology and received 18F-PSMA PET/CT and mpMRI during September 2018 to May 2021 in our hospital were retrospectively studied. The median age was 68(64-75), with the median PSA level of 14.74(7.75-24.19)ng/mL. All patients received mpMRI before biopsy. On biopsy, 6(12.2%) patients had International Society of Urological Pathology grade group(ISUP GG) 1 diseases, 16(32.7%) had ISUP GG 2 diseases, 12(24.5%) had ISUP GG 3 diseases, and 15(10.9%) had ISUP GG 4 or 5 diseases. Patients were then divided into high-grade group (ISUP 4-5) and low-grade group(ISUP 1-3). The median age of patients in high-grade group and low-grade group were 65(62-76) and 71(65-74), respectively. The PSA level in high-grade group and low-grade group were 15.11(6.63-42.86) ng/ml and 12.31(7.94-18.25) ng/ml, respectively. No significant differences were found in age and PSA level between the two groups ( P=0.334, P=0.448). All patients underwent 18F-PSMA PET/CT within 4 weeks after biopsy. The maximum standardized uptake value(SUV max) and the minimum apparent diffusion coefficient(ADC min)were recorded, and the ratio of SUV max/ ADC minwere calculated. The correlation between the above parameters and ISUP grade group were analyzed.The diagnostic value of the parameters was evaluated by the receiver operating characteristic (ROC) curve. Results:The data of 49 patients were analyzed. The average ADC minwas (0.57±0.16)×10 -3 mm 2/s, with the average SUV max and SUV max/ADC min of 15.30±12.54 and (29.69±23.72)×10 3, respectively. Statistical differences were found in SUV max ( P=0.012) and SUV max/ADC min ( P=0.002) between the high- and low-grade groups, while ADC min ( P=0.411) showed no statistical differences between the two groups. Significant positive correlations were found between SUV max(r=0.501, P<0.001), SUV max/ADC min (r=0.527, P<0.001) and ISUP grade group, respectively. There was a negative correlation between ADC min and ISUP grade group (r=-0.296, P=0.039). SUV max/ADC min was the best index to distinguish high-grade group from low-grade group prostate cancer with the area under the curve(AUC) of 0.749. In contrast, the AUC of SUV maxand ADC min were 0.731 and 0.615, respectively. The diagnostic sensitivity and specificity of SUV max/ADC min were 73.3% and 85.3%, respectively, with a critical value of 37.23×10 3. Conclusion:The combination use of 18F-PSMA PET/CT and mpMRI could improve the diagnostic efficiency for prostate cancer, compared to either modality alone. The ratio of SUV max/ADC min has a positive correlation with ISUP grade group, and is a promising index for distinguishing the high-grade prostate cancer from low-grade cancer.

Dosimetric study of 125I seed implantation guided by 4D template for advanced malignant tumors / 中华放射肿瘤学杂志

Objective:To investigate the safety and dose of 4D template (real-time adjustable angle template) in the treatment of advanced malignant tumors with 125I seeds. Methods:98 patients with advanced malignant tumors admitted to Department of Thoracic Surgery of Shaanxi Provincial Tumor Hospital were treated with 4D template-navigated radioactive 125I seed implantation from June 2018 to December 2019. Preoperative TPS plan, intraoperative optimization, postoperative verification of immediate dose and postoperative evaluation of implantation dose were performed. The treatment results were observed. Results:All 98 patients completed the seed implantation. The implantation dose of GTV of implantation site receiving external irradiation was (12 489±414) cGy and the dose of no external irradiation was (15 036±514) cGy. V 100% was 84.7%-94.1%, and 88.2%-93.7%. The implantation dose of CTV was (7 450±621) cGy, and (9 080±761) cGy. The quality of dose implantation was evaluated as: excellent in 89 cases (91%, 89/98), good in 7 cases (7%, 7/98), fair in 2 cases (2%, 2/98), and poor in 0 case, respectively. The symptom relief rate of patients with pain was 92%(36/39). The 1-and 2-year local control rates were 61%, 36% and 82%, 54% in patients treated with and without external irradiation, respectively. The difference was statistically significant ( P=0.02). The incidence rates of pneumothorax and hemoptysis were 19%(9/48) and 10%(5/48). No corresponding complications were observed in other parts of the patients. Conclusion:4D template-assisted 125I seed therapy is safe and effective for malignant tumors, and intraoperative adjustment of needle angle and dose optimization can realize the precise control of implantation dose.

Establishment of a culture system for human nasal mucosa organoids with controllable differentiation / 南方医科大学学报

OBJECTIVE@#To establish a culture system for human nasal mucosal organoids with controllable differentiation to reproduce the structure and function of the source tissue through staged expansion-differentiation culture.@*METHODS@#Fresh samples of surgically resected middle turbinate and nasal polyp tissues were collected, from which the nasal mucosa epithelial cells were isolated by enzymatic digestion and filtration for continuous culture at the air-liquid interface for expansion (EO group) or staged culture for expansion and differentiation (DO group). Immunohistochemical staining was used to characterize the structure, cellular composition and ciliary function of nasal mucosal organoids in the two groups. The secretion function of the differentiated nasal mucosal organoids in DO group was evaluated using PAS staining.@*RESULTS@#Both of the two organoid culture systems yielded vacuolar or solid spherical 3D organoids, and their diameters increased progressively with time. On day 16 of culture, more vacuolar organoids occurred in DO group, while more solid spherical organoids were seen in EO group, and the proportion of vacuoles was significantly greater in DO group than in EO group [(54.67±13.26)% vs (21.67±8.57)%, P < 0.05]. Short tandem repeat (STR) test of the nasal mucosal organoids and the source tissue showed a 100% match between them. On day 21 of culture, scanning and transmission electron microscopy of the nasal mucosal organoids identified ultrastructure of cilia in DO group and short villi structure in most of the organoids in EO group. Immunohistochemical staining showed positivity for P63 (basal cells), β-tubulin (ciliated columnar cells), and MUC5AC (goblet cells) in the organoids. Compared with those in EO group, the organoids in DO group showed significantly greater percentages of ciliated cells [(7.95±1.81)% vs (27.04±5.91)%, P < 0.05] and goblet cells [(14.46±0.93)% vs (39.85±5.43)%, P < 0.05) with a similar percentage of basal cells [(56.91±14.12)% vs (53.42±15.77)%, P > 0.05]. The differentiated nasal mucosal organoids in DO group were positively stained for glycogen.@*CONCLUSION@#The staged expansion-differentiation culture method allows more stable and prolonged growth of the cultured cells in vitro to produce organoids with controllable differentiation closely resembling the morphological structure and functions (ciliary function and secretory function) of the source tissue.

Retrospective analysis on 77 cases of T4b hypopharyngeal carcinoma treated by non-surgical treatments / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.

Clinical application of minimal invasive liposuction system in thigh areas of liposuction / 中华医学美学美容杂志

Objective:To investigate the clinical application and surgical effect of minimal invasive liposuction system (MILS) method in the thighs liposuction.Methods:From July 2019 to March 2021, 868 patients were selected for thigh liposuction. Local anesthesia and intravenous anesthesia were used in all operations. The preoperative design and intraoperative procedures were carried out according to the requirements of MILS ? method. There was an average of 2 154.4 ml fat aspirated, and the average operation time was 156.8 min. Results:After 2-18 months of follow-up, 83.3% of the patients were discharged on the day of operation. The thigh line curve of the patients was fluent and the perimeter of upper thigh was significantly reduced. The satisfactory rate was 92.3%, and the incidence of complications was 2.8%. No severe complication occurred.Conclusions:MILS method is a safe and effective procedure to partition thighs liposuction area scientifically and finely. The MILS method makes the lumbar abdominal liposuction operation standardized, reduces unnecessary operation, shortens the liposuction learning curve, reduces the occurrence of complications, and achieves the best aesthetic effect.

The preliminary study about feasibility and accuracy of the frozen section during targeted prostate biopsy / 中华泌尿外科杂志

Objective:To investigate the feasibility and reliability of the frozen section during targeted prostate biopsy.Methods:The clinical and pathological information of patients who received cognitive fusion transperineal targeted plus systematic biopsy and frozen section of 1-2 core targeted biopsy were consecutively collected and retrospectively studied. The median age was 70 (ranging 64-78) years, with the median prostate-specific antigen (PSA) level of 11.00 (ranging 6.63-16.52) ng/ml and the median prostate volume of 35.72 (ranging 22.59-47.71) ml. All patients received bi-parametric magnetic resonance imaging (bp-MRI) and have Prostate Imaging Reporting and Data System (PI-RADS) 3 or higher lesions diagnosed on bp-MRI. The suspected lesions would be taken by targeted biopsy of which one or two cores would be sent to prepare for the frozen sections. Then a cognitive fusion targeted and systematic biopsy covering the above targeted zones would be routinely administered under a transperineal approach as a standard protocol. The total time used for diagnosis of the frozen sections, the pathological diagnosis and the International Society of Urological Pathology (ISUP) grade groups (GG) would be recorded. The sensitivity, the positive predictive value, and the accuracy on grade groups would be analyzed, using the pathological diagnosis based on standard sections from the same targeted lesion.Results:A total of 29 patients were included in this study. Accordingly, 29 suspected lesions were identified on bp-MRI. A total of 20 lesions were finally diagnosed of PCa on frozen section, with the detection rate of 69.0%. Of those, 9(45.0%) cases were ISUP GG 1 diseases, 5(25.0%) cases were GG 2 diseases, 1(5.0%) case was GG 3 disease, and 5(25.0%) cases were GG 4-5 diseases. A total of 22 lesions were diagnosed with PCa on standard sections of cores from the same targeted lesions, with the detection rate of 75.9%. Of those, 6(27.3%) cases were GG 1 disease, 11(50.0%) cases were GG 2 diseases, 1(4.5) case was GG 3 disease, and 4(18.2%) cases were GG 4-5 diseases. The sensitivity and the positive predictive value of frozen section were 90.9% and 100%, respectively. No false positive diagnosis was made by frozen section. Compared to diagnosis from frozen sections, the GG diagnosed from final standard sections were found to upgrade and downgrade in 2 and 2 cases, respectively. The accuracy rate on GG of frozen sections was 80%. The time used for the diagnosis of frozen sections was (11±2) minutes. The histology quality control of four specimens was dissatisfactory. Two were due to tissue loss and deformation during sampling, and the other two were due to cytoclasis during low-temperature transferring.Conclusion:It is feasible and reliable to make a pathological diagnosis from frozen section of prostate targeted biopsy.

Liraglutide Inhibits High Glucose⁃induced Injury of Mouse Islet Cells / 中国生物化学与分子生物学报

Liraglutide is an analog of glucagon⁃like peptide⁃1 and plays an important role in the treatment of diabetes. But the specific mechanism of liraglutide in improving the function of pancreatic β cells is still unclear. Therefore, high glucose (33 mmol/ L) was used to induce islet MIN6 cells for 48 hours to establish a high glucose injury model in this study. The CCK⁃8 assay was used to detect cell viability, and the results showed that the viability of MIN6 cells in the high glucose group decreased (P<0. 05) compared with the control group, and the cell viability increased after liraglutide treatment (P<0. 05). Using the mouse insulin detection kit and ATP content detection kit, we found that both the insulin re⁃ lease (P<0. 01) and ATP content decreased (P<0. 001) in the high glucose group compared with the control group, and after liraglutide treatment both insulin release (P < 0. 05) and ATP content (P < 0. 001) increased. We used the mitochondrial membrane channel pore (MPTP) fluorescence detection kit in MIN6 cells and found that the green fluorescence intensity of the high glucose group was significant⁃ ly decreased (P<0. 001) compared with the control group, and after liraglutide treatment the green fluo⁃ rescence intensity was significantly increased (P<0. 001). The DCFH⁃DA probe combined with flow cy⁃ tometry was used to detect the level of reactive oxygen species (ROS). We found that compared with the control group, the ROS level in the high glucose group was significantly increased (P<0. 001), and de⁃ creased by liraglutide treatment (P<0. 01). Intracellular malondialdehyde (MDA) contents, superoxide dismutase (SOD) and catalase (CAT), and lactate dehydrogenase (LDH) activities in the cell superna⁃ tant were measured, and the levels of MDA and LDH were significantly increased (P<0. 05), and the levels of SOD and CAT were significantly decreased (P<0. 01) in the high glucose group compared with the control group. After liraglutide treatment, the levels of MDA and LDH were decreased (P<0. 05), and the levels of SOD and CAT were increased (P<0. 05). The results of Western blotting showed that the expression of UCP2 was upregulated in the high glucose group (P<0. 01) compared with the control group, and after liraglutide treatment the expression of UCP2 decreased (P<0. 05). The results indica⁃ ted that liraglutide has significant effects in high⁃glucose induced mitochondrial damage, oxidative stress and insulin secretion in MIN6 cells, which will provide a theoretical basis for clinical utilization of liraglu⁃ tide.

Risk assessment of public health emergencies in Zhejiang Province, March 2021 / 预防医学

Objective@#To assess the risk of public health emergencies in Zhejiang Province, March 2021. @*Methods@#An expert counsel was conducted to assess the risk of coronavirus disease 2019 ( COVID-19 ) , enteritis due to norovirus, chicken pox and influenza by professionals in Zhejiang CDC, based on the information from infectious disease and public health emergency surveillance in Zhejiang Province, domestic health administrative departments, World Health Organization, and European CDC. @*Results@#In March 2021, the risk of imported COVID-19 epidemic will be high in Zhejiang Province, and the possibility of local spread could not be ruled out. The possibility of a large-scale outbreak of enteritis due to norovirus and a small-scale outbreak of chickenpox in schools and kindergartens could not be ruled out after the new term begins. An increased risk of influenza epidemic is predicted in collective units such as schools and kindergartens, yet the risk of a large-scale one will be low.@*Conclusion@#High attention should be paid to COVID-19 and enteritis due to norovirus, and general attention should be paid to chicken pox and influenza outbreak.

Advances of research on oxygen-enhancing nano-delivery system for photodynamic therapy / 中国药科大学学报

@#Photodynamic therapy, a new type of non-invasive treatment, is based on the principle that the photosensitizer excited by laser can transfer energy to oxygen, which generates cytotoxic singlet oxygen and thus induce tumor cell apoptosis or necrosis. As an oxygen-dependent therapy, the antitumor effect of photodynamic therapy is obviously limited by hypoxia environment of solid tumor tissue. Therefore, reversing and improving the hypoxia of tumor tissue can significantly enhance the efficacy of photodynamic therapy. This review focuses on the progress of tumor oxygenation strategy mediated by nano-delivery system, including direct oxygen delivery strategies, catalytic oxygen production strategies, responsive material in situ oxygen supply strategies and microorganism oxygen supply strategies, aiming to improve the antitumor effect of photodynamic therapy. It provides new ideas and new approaches for further study of oxygen-enchancing nano-delivery system for photodynamic therapy.

Analysis of virus subtype variation among HIV/AIDS in Wuxi city, 2014-2016 / 中华微生物学和免疫学杂志

Objective:To investigate the variation characteristics and influencing factors of HIV/AIDS subtypes in Wuxi city of Jiangsu Province from 2014 to 2016.Methods:HIV/AIDS population in Wuxi city in 2014 was selected as the research object, and the HIV molecular epidemiology and follow-up study were carried out. Collect epidemiological information, extract DNA from blood samples, amplify pol gene fragment by nest-PCR and sequence, use ChromasPro 1.6 software and MEGA 7.0 software to construct the HIV-1 sequence database, and use FastTree2.1.10 software to construct the phylogenetic tree to confirm the subtype; in 2016, the same population was followed up, and the HIV subtype variation was analyzed, and the influencing factors of subtype variation were explored by multivariate logistic regression. Results:A total of 612 HIV/AIDS cases in 2014 and 2016 were collected. The age of the subjects was mainly 30 years old or above (85.46%, 523/612), and the proportion of people over 50 years old was higher (228/612, 37.25%). The main route of transmission was homosexuality, accounting for 49.67%. A total of 1224 samples were detected and CRF01 _ AE、CRF07_ BC、B、CRF08_ BC、CRF67_ 01B、CRF55_ 01B、CRF68_ 01B, 7 subtypes of HIV-1 and 5 unique recombinant types (URFs) was detected. CRF01_ AE and CRF07_ BC was still the main genotype in Wuxi, Jiangsu Province, accounting for 66.75%. There were 29 cases (3.56%) of URFs recombinant strains. During 2014-2016, the variation rate of subtypes was 14.63%, and the most common variation was CRF01_ AE changes to CRF07_ BC(13.95%). Marital status (OR=0.363, 95% CI: 0.137-0.964) and baseline CD4 level (OR=0.414, 95% CI: 0.192-0.891) were associated with subtype variation.Conclusions:The HIV-1 subtypes of HIV/AIDS patients in Wuxi city are diverse and complex, the proportion of recombinant subtypes is rising, the URFs that are difficult to determine the genotype increase significantly, and the variation rate of HIV-1 subtypes among HIV/AIDS infected people is high. It is necessary to strengthen the monitoring of HIV-1 subtypes.

Role of dendritic cells in host immunity to herpes simplex virus and possible mechanisms / 中华微生物学和免疫学杂志

Herpes simplex virus (HSV) is a double-stranded DNA virus that can infect skin and mucosal epithelial cells. It can establish latency in sensory neurons and sporadically reactivate from these cells. In order to reply to attacks of the host and evade the immunity surveillance during infection and reactivation, HSV has developed a multitude of clever strategies. Dendritic cells (DCs), one of the most important antigen-presenting cells (APC), can recognize pathogens at the infection sites and activate specific T cells, thus playing a crucial role in the host immunity against virus infection. This paper reviewed the mechanism of the host immunity against HSV, especially the role of DCs in HSV-induced immune responses and the future research perspective.