Establishment and evaluation of in vitro galectin-3 inhibitor screening model / 药学学报

Galectin-3 (Gal-3) belongs to the galectin family and is specific in binding β-galactoside. Through its C-terminal domain, Gal-3 binds to the galactoside group of the glycosylated insulin receptor (IR) and inhibits IR signaling pathway, which leads to the insulin resistance. Thus, Gal-3 is a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes. Here we report a simple Gal-3 screening model based on the property that Gal-3 binds to the galactoside. We expressed and purified human Gal-3 in Escherichia coli (E.coli), and labeled it with fluorescein isothiocyanate (FITC) in vitro. After incubating FITC labeled Gal-3 (Gal-3-FITC) with PANC-1 cells, which express glycosylated membrane protein, PANC-1 cells started to show green fluorescent signal due to the Gal-3-FITC binding to the glycosylated membrane protein. Gal-3 inhibitor disrupts the binding of Gal-3-FITC and PANC1 cells, subsequently leads to the decrease of the fluorescent signal in PANC-1 cells. We can evaluate the inhibitory efficiency of Gal-3 inhibitors through measurement of the fluorescent signal. Further studies show this model is simple, stable, and repeatable with a Z' factor between 0.7 and 0.85. In sum, we have successfully established an in vitro high-throughput screening model for Gal-3 inhibitors.

Quality control of the technology method of clinical comprehensive drug evaluation / 中国药房

At present， there are still some problems in China’s clinical comprehensive drug evaluation， such as the unscientific design of the evaluation content， the nonstandard evaluation method and organizational process， and the evaluation results not meeting the decision-making needs. It is urgent to carry out quality control over the whole process of the clinical comprehensive drug evaluation project. From the technical point of view， the quality control methods of clinical comprehensive drug evaluation are discussed through three links of the evaluation content and design （giving the quality control key points of the theme selection process and scheme design）， the evaluation method （discussing the quality control elements of two common evaluation methods， i. e. documentary evidence method and real-world research） and result application transformation （giving suggestions on quality control from the comprehensive analysis of evaluation results， transformation of evaluation results and decision-making）， so as to promote the quality improvement of clinical comprehensive drug evaluation.

Acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy based on data mining technology / 中国针灸

OBJECTIVE@#To analyze the acupoint selection rules of acupuncture and moxibustion for post-stroke epilepsy by data mining technology.@*METHODS@#The literature regarding acupuncture and moxibustion for post-stroke epilepsy included in CNKI, VIP, Wanfang, SinoMed and PubMed databases from the establishment of the database to August 1st 2022 was retrieved. Microsoft Excel 2019 software was used to establish a database to conduct the descriptive analysis of acupoints; SPSS Modeler 18.0 Apriori algorithm was used to conduct association rule analysis; high-frequency acupoint co-occurrence network diagrams were drawn by Cytoscape3.9.0 software; SPSS Statistics 25.0 software was used to perform hierarchical cluster analysis on high-frequency acupoints and a tree diagram was drawn.@*RESULTS@#Totally 39 articles were included, and 63 prescriptions of acupuncture and moxibustion were extracted, involving 56 acupoints, with a total frequency of 516 times; the top three acupoints with the highest frequency of use were Baihui (GV 20), Fenglong (ST 40) and Neiguan (PC 6); the selected meridians were mainly the governor vessel, the hand and foot yangming meridians; the selection of acupoints were mostly in the head, neck and lower limbs; in terms of acupoint compatibility, Hegu (LI 4)-Shuigou (GV 26) and Neiguan (PC 6) had the highest confidence degree; The top 20 high-frequency acupoints could be divided into 4 effective clusters.@*CONCLUSION@#Modern acupuncture and moxibustion treatment for post-stroke epilepsy attaches great importance to the use of yang meridians and meridians with enrich qi and blood; the core prescription is Shuigou (GV 26)-Neiguan (PC 6)-Hegu (LI 4)-Baihui (GV 20). In addition, the combination of distant and near acupoints is highly valued to improve clinical efficacy.

Epidemiological characteristics and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City / 中国血吸虫病防治杂志

Objective To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City. Methods Children with diarrhea under 5 years of age admitted to Guangzhou Children’s hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children’s Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants’ demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis. Results A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio (OR) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [OR = 4.221, 95% CI: (1.043, 17.087)], antibiotic use [OR = 0.125, 95% CI: (0.017, 0.944)] and chronic diarrhea [OR = 2.172, 95% CI: (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City. Conclusions B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.

Comparative study on the methods to determine disintegration time of oral soluble films / 药学学报

Disintegration time is a key parameter that affects the palatability and compliance of oral soluble films. At present, there is no standard method to determine the disintegration time of oral soluble films. In this study, we compared the six methods (pharmacopoeial disintegration method, petri dish method, sponge surface method, slide frame and ball method, partially immersed into liquid (without weight attached) and partially immersed into liquid (with weight attached)) to determine the in vitro disintegration time of oral soluble films with different thickness, and evaluated the correlation with the in vivo disintegration time. The results showed that the repeatability and correlation of pharmacopoeial disintegration method and the partially immersed into liquid method (with weight attached) were excellent, with the endpoint of disintegration testing easy to determine. Partially immersed into liquid method (with weight attached), properly simulating the physiological condition in oral cavity, showed strong operability, good repeatability and in vitro-in vivo correlation, and was suitable for in vitro disintegration evaluation of oral soluble film dosage form. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Efficacy of W-genioplasty on the broad and short chin / 中华医学美学美容杂志

Objective:To investigate the clinical effect of W-shaped genioplasty in the correction of broad and short chin deformity.Methods:Thirty-eight patients (5 males, 33 females, aged 20 to 41 years, mean 27.3 years) complained with broad and short chin were admitted to the Affiliated Friendship Plastic Surgery Hospitalof Nanjing Medical University from January 2019 to December 2021. CBCT scan and three-dimensional reconstruction were performed to design osteotomy line and determine the distance of chin lengthening, narrowing and advancing or retrocession preoperatively. Under general anesthesia, the W-shaped osteotomy was performed using an intraoral incision, and the angle between the bilateral free bone fragments, the distance of downward and forward movement were adjusted to change the curvature, width, length and prominence of the lower edge of the chin according to the preoperative designs. The results were evaluated by clinical appearances and image analyses at a follow-up of 3-24 months.Results:The amount of vertical lengthening of the chin in 38 cases were 2 mm to 5 mm, with an average of 3.02 mm. The horizontal narrowing width distances were 3-7 mm, with an average of 5.6 mm. The patients were followed up for 3-24 months, with an average of 10.6 months. There were no complications such as hematoma, wound dehiscence, accidental fracture, surgical area infection and permanent neurosensory disorder. 38 patients had transient sensory loss in the lower lip region of varying degrees, but all recovered spontaneously during routine follow-up period. All patients were satisfied with the improvement of facial contour.Conclusions:W-shaped geinoplasty preserves the central bone of the chin and the attachment of genioglossus muscle, which does not affect the normal anatomy and physiological function of the oral cavity. After osteotomy, the bone is removed and the bilateral bone fragments move flexibly. It can effectively change the radian, width, length and protrusion of the lower edge of the chin in three dimensions, so as to correct the wide and short deformity of the chin.

Signal transducer and activator of transcription 6 mediates skeletal muscle cell injury in septic mice by regulating ferroptosis / 中华危重病急救医学

Objective:To explore the effect of signal transducer and activator of transcription 6 (STAT6) on ferroptosis in skeletal muscle cells in sepsis model and its potential mechanism.Methods:Twenty-four 8-week-old male specific pathogen free Kunming mice were divided into normal control group, sham group, sepsis model group and STAT6 inhibitor pretreatment group according to random number table method with 6 mice in each group. A mouse sepsis model was reproduced by cecal ligation and perforation (CLP). In the sham group, the skin of mice was sutured after exposing the cecum tissue. In the STAT6 inhibitor pretreatment group, 10 mg/kg AS1517499 was injected intraperitoneally 1 hour before model reproduction. The sham group and the model group were intraperitoneally injected with the same volume of normal saline. Mice in the normal control group did not receive any operation or drug intervention. The mice were sacrificed 24 hours after model reproduction, and the muscle tissue of hind limb was obtained under sterile condition. Hematoxylin-eosin (HE) staining was used to observe the histopathology with optical microscope, and mitochondrial morphological changes were observed by transmission electron microscopy after double staining with uranium acetate lead citrate. The ferroptosis marker proteins expressions of chitinase-3-like protein 1 (CHI3L1), cyclooxygenase-2 (COX-2), acyl-CoA synthetase long-chain family member 4 (ACSL4), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPx4) were detected by Western blotting.Results:Under the optical microscope, the morphology and structure of skeletal muscle tissues in the normal control and sham groups were normal. In the model group, the structure of skeletal muscle tissues was loose, the muscle fiber became smaller and atrophic, inflammatory cell infiltration and even muscle fiber loss were found. Compared with the model group, the structure of skeletal muscle tissues was tight and skeletal muscle atrophy was improved in the STAT6 inhibitor pretreatment group. The ultrastructure of skeletal muscle cell in the normal control and sham groups was normal under transmission electron microscope. The ultrastructure characteristics of skeletal muscle in the model group showed that cell membrane was broken and blister, mitochondria became smaller and membrane density increased, the mitochondrial crista decreased or disappeared, the mitochondrial outer membrane was broken, and the nucleus was normal in size but lacked chromatin condensation. Compared with the model group, the STAT6 inhibitor pretreatment group had a significant improvement in the ultrastructure of muscle cells. Compared with the normal control and sham groups, the protein expressions of CHI3L1, COX-2, ACSL4 and FTH1 in the muscle of the model group were significantly increased, while the protein expression of GPx4 was decreased significantly, indicating that the skeletal muscle cells in the mouse sepsis model showed characteristic mitochondrial injury and abnormal expression of ferroptosis markers. Compared with the model group, the protein expressions of CHI3LI, COX-2, ACSL4 and FTH1 in the STAT6 inhibitor pretreatment group were significantly decreased [CHI3L1 protein (CHI3L1/GAPDH): 0.70±0.08 vs. 0.97±0.09, COX-2 protein (COX-2/GAPDH): 0.61±0.03 vs. 0.83±0.03, ACSL4 protein (ACSL4/GAPDH): 0.75±0.04 vs. 1.02±0.16, FTH1 protein (FTH1/GAPDH): 0.49±0.06 vs. 0.76±0.13, all P < 0.05], while the protein expression of GPx4 was significantly increased (GPx4/GAPDH: 1.14±0.29 vs. 0.53±0.03, P < 0.05). Conclusions:Sepsis can induce ferroptosis in skeletal muscle cells of mice. STAT6 may mediate ferroptosis in mouse skeletal muscle cells by regulating the expressions of COX-2, ACSL4, FTH1 and GPx4, thereby inducing skeletal muscle cell injury in sepsis.

Analysis of current status and risk of development in occupational medical examination institutions in Guangdong Province / 中国职业医学

Objective: To analyze the status of occupational medical examination (OME) institutions in Guangdong Province and the critical control points affecting their future development. Methods: A total of 211 OME institutions registered in Guangdong Province were selected as the research subjects. Their current statue was investigated, and the risk assessment of their future development was carried out based on hazard analysis and critical control point theory. Results: The OME institutions were mainly concentrated in the Pearl River Delta, accounting for 72.0%. The public and private medical and health institutions accounted for 70.6% and 29.4% respectively. The filing rates of different OME categories from high to low in the order were physical factors, chemical factors, dust, other, radiation factors, biological factors (P<0.01), and the filing rates were 89.6%, 88.6%, 84.8%, 63.0%, 7.1% and 1.0%, respectively. The rates of excellence in the field assessment from high to low in the order were hearing atlas analysis personnel, lung function examination operators, chest film reading personnel, chief examination physician, technical director, quality director (P<0.01), and the rates of excellence were 49.4%, 26.2%, 20.6%, 10.8%, 8.2% and 4.6%, respectively. A total of 37 institutions did not submit OME information, of which 23 institutions did not carry out OME work after filing. The required diagnosis rate and confirmed diagnosis rate of suspected occupational diseases in 2020 were 34.3% and 55.3%, respectively. In 2021, the detection rate of suspected occupational diseases was only 1.1‰. Among the institutions with biological monitoring records, 64.1% did not participate in external quality assessment program in laboratory, and the unqualified rate of 38 participating institutions was 55.3%. The risk assessment results show that the future development of OME institutions needs to focus on private institutions, institutions that have not reported OME information, institutions that have missed diagnosis and missed reporting of suspected occupational diseases, institutions that have not participated in external quality assessment program in laboratory and core personnel such as quality managers, technical leaders, and main inspection physicians. Conclusion: OME institutions in Guangdong Province show the characteristics of centralized filing category, centralized filing region and centralized filing institution nature. Combined with the potential risks of OME institutional capacity building, it is necessary to implement classified management, strengthen information construction, supervision and management, implement post responsibilities, and promote the high-quality development of OME institutions.

Cholesterol paradox in the community-living old adults: is higher better? / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.@*METHODS@#A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.@*RESULTS@#A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.@*CONCLUSIONS@#In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Effects of Long-acting Injectable 3-Monthly Paliperidone Palmitate on the Clinical and Social Performance of Patients with Schizophrenia

Objective@#To investigate the effects of long-acting injectable 3-monthly paliperidone palmitate on the clinical and social functioning of patients with schizophrenia. @*Methods@#This study enrolled patients with schizophrenia receiving long-acting injectable 1-monthly paliperidone palmitate for at least 4 months and who subsequently received 3-monthly paliperidone palmitate. Accordingly, 418 patients were followed up for 24 weeks. Their clinical symptoms and social functioning were measured using the Clinical Global Impression-Severity of Illness and Personal and Social Performance scales. @*Results@#The Personal and Social Performance total score was significantly higher after 3-monthly paliperidone palmitate treatment than at baseline (baseline vs. week 24: 54.3 ± 18.0 vs. 61.0 ± 14.5 [mean ± standard deviation]; p ＜ 0.001; Wilcoxon signed-rank test); the proportion of patients in the mildly ill group (scores 71−100) also increased significantly (baseline vs. week 24: 16.5% vs. 20.6%; p＜ 0.001; McNemar-Bowker test). The mean Clinical Global Impression-Severity of Illness score decreased significantly (baseline vs. week 24: 3.7 ± 1.0 vs. 3.4 ± 0.9; p＜ 0.001; Wilcoxon signed-rank test), as did the proportion of patients in the severely ill group (baseline vs. week 24: 4.1% vs. 2.1%; p ＜ 0.001; McNemar-Bowker test). @*Conclusion@#Continuous 3-monthly paliperidone palmitate treatment significantly enhances the personal and social performance of patients with schizophrenia and reduces the proportion of those with severe illness. These findings suggest that long-acting injectable antipsychotic administration at intervals longer than 1 month might improve the social functioning of and promote return to activities of daily living in patients with schizophrenia.

Construction of drug clinical comprehensive evaluation index system and quantitative grading by using analytic hierarchy model / 中国药房

OBJECTIVE To construct the drug clinical comprehensive evaluation index system and quantitative grading in China， and to provide a reference for scientifically carrying out comprehensive clinical evaluation of drugs. METHODS The analytic hierarchy model was used to establish the drug clinical comprehensive evaluation index system， the weight of the evaluation index and the quantitative grading of each index were determined through expert consultation and model calculation. RESULTS The results of expert consultation were integrated by using the analytic hierarchy model， and the drug clinical comprehensive evaluation index system was obtained： including six first-level indicators of effectiveness， safety， economy， suitability， accessibility and innovation， as well as twenty-three second-level indicators of recommended status， medication for special populations， and drug treatment costs； the weight of each indicator was calculated through estimation-matrix method. CONCLUSIONS The analytic hierarchy model can construct the drug clinical comprehensive evaluation index system and quantitative grading in China， which can provide methodological references for comprehensive analysis and decision-making， thus making the clinical comprehensive evaluation of drugs completer and more scientific.

Targeting fibroblast activation protein inhibits endothelial-mesenchymal transition by affecting cancer-associated fibroblasts derived exosomes / 中国药理学通报

Aim To investigate whether targeted inhibition of fibroblast activation protein (FAP) can inhibit the endothelial-to-mesenchymal transition (EndMT) of vascular endothelial cells by affecting exosomes (Exo) of cancer-associated fibroblasts (CAFs) and explore the underlying mechanisms. Methods Primary CAFs and peri-tumor fibroblasts (PTFs) were obtained from lung cancer and peri-cancer tissues, and CAFs-exo and PTFs-exo were collected from culture medium, respectively. Exosomes from CAFs treated with specific FAP inhibitor (3.3 nmol • L-

Residual coronary artery tree description and lesion EvaluaTion (CatLet) score, clinical variables, and their associations with outcome predictions in patients with acute myocardial infarction / 中华医学杂志(英文版)

BACKGROUND@#We have recently developed a new Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system. Our preliminary studies have demonstrated its superiority over the the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery (SYNTAX) score with respect to outcome predictions for acute myocardial infarction (AMI) patients. The current study hypothesized that the residual CatLet (rCatLet) score predicts clinical outcomes for AMI patients and that a combination with the three clinical variables (CVs)-age, creatinine, and ejection fraction, will enhance its predicting values.@*METHODS@#The rCatLet score was calculated retrospectively in 308 consecutively enrolled patients with AMI. Primary endpoint, major adverse cardiac or cerebrovascular events (MACCE) including all-cause mortality, non-fatal AMI, transient ischemic attack/stroke, and ischemia-driven repeat revascularization, was stratified according to rCatLet score tertiles: rCatLet_low ≤3, rCatLet_mid 4-11, and rCatLet_top ≥12, respectively. Cross-validation confirmed a reasonably good agreement between the observed and predicted risks.@*RESULTS@#Of 308 patients analyzed, the rates of MACCE, all-cause death, and cardiac death were 20.8%, 18.2%, and 15.3%, respectively. Kaplan-Meier curves for all endpoints showed increasing outcome events with the increasing tertiles of the rCatLet score, with P values <0.001 on trend test. For MACCE, all-cause death, and cardiac death, the area under the curves (AUCs) of the rCatLet score were 0.70 (95% confidence intervals [CI]: 0.63-0.78), 0.69 (95% CI: 0.61-0.77), and 0.71 (95% CI: 0.63-0.79), respectively; the AUCs of the CVs-adjusted rCatLet score models were 0.83 (95% CI: 0.78-0.89), 0.87 (95% CI: 0.82-0.92), and 0.89 (95% CI: 0.84-0.94), respectively. The performance of CVs-adjusted rCatLet score was significantly better than the stand-alone rCatLet score in terms of outcome predictions.@*CONCLUSION@#The rCatLet score has a predicting value for clinical outcomes for AMI patients and the incorporation of the three CVs into the rCatLet score will enhance its predicting ability.@*TRIAL REGISTRATION@#http://www.chictr.org.cn , ChiCTR-POC-17013536.

Acupoint selection rules of staging, syndrome types, and symptoms of acupuncture for peripheral facial paralysis based on data mining / 中国针灸

OBJECTIVES@#To analyze and explore the acupoint selection rules of different staging, syndrome types, and symptoms of acupuncture for peripheral facial paralysis based on data mining.@*METHODS@#Literature regarding acupuncture for peripheral facial paralysis was retrieved in CNKI, VIP, Wanfang, SinoMed, and PubMed from January 1, 2012, to December 31, 2021. The Traditional Chinese Medicine Inheritance Assistant Platform (V 3.0), SPSS Modeler 18.0, and Cytoscape software were used to analyze the selection of acupoints based on staging, meridian distribution of acupoints, the selection of acupoints based on syndrome types, syndrome types based on staging, and symptom-based acupoint selection. Association rule analysis was performed for each stage and major syndrome types, and co-occurrence network diagrams were generated.@*RESULTS@#A total of 1 695 articles were included, involving 124 acupoints with a total frequency of 5 456 times. Among 1 080 articles related to staging-based acupoint selection, the acute stage had the highest acupoint use frequency (2 224 times) and number (88 acupoints). Among all stages, the acupoints of the stomach meridian of foot-yangming were most frequently used, with Dicang (ST 4)-Yangbai (GB 14) and Dicang (ST 4)-Jiache (ST 6) being the high-frequency acupoint pairs in each stage. The top four syndrome types in terms of acupoint usage frequency were wind-cold syndrome, wind-heat syndrome, qi-blood deficiency syndrome, and liver-gallbladder damp-heat syndrome. Among 521 articles combining staging with symptoms or syndrome types with symptoms for acupoint selection, the symptom "nasolabial groove becoming shallow or disappearing" had the highest frequency of occurrence. The symptoms with the highest acupoint usage frequency and number were "forehead wrinkles becoming shallow or disappearing" and "pain behind the ear" respectively.@*CONCLUSIONS@#Acupoint selection for peripheral facial paralysis primarily focuses on the yang meridians in each stage, supplemented by local acupoints and based on the pathological characteristics. Syndrome differentiation and treatment should be prioritized, combined with local acupoint selection. Clinical acupoint selection can be based on a combination of staging, syndrome types, and symptoms.

Distribution characteristics of newly reported occupational welder′s pneumoconiosis in Guangdong Province, 2013-2022 / 中国职业医学

Objective To analyze the distribution features of newly reported cases of occupational welder′s pneumoconiosis (OWP) in Guangdong Province from 2013 to 2022. Methods Data of newly reported cases of OWP from National Occupational Disease Network Direct Reporting System of Guangdong Province from 2013 to 2022 was analyzed using conventional data analyzing Methods. Results A total of 294 cases of OWP were reported in Guangdong Province from 2013 to 2022 with an overall downward trend. The average age at diagnosis for new OWP cases was 44±6 years old, and the median of dust exposure duration was 11 years. Males accounted for 99.3% of the cases, and 94.2% of the cases were phase Ⅰ OWP. Guangzhou City had the highest regional distribution with 74.8% of the cases. The industry distribution was mainly manufacturing, accounting for 86.7% of the cases. The scale of enterprises was most common in small enterprises, followed by large and medium-sized enterprises, accounting for 38.4%, 30.6% and 24.5% of the cases respectively. The economic types of enterprises were mostly private enterprises, followed by state-owned enterprises, accounting for 54.1% and 32.0% of the cases respectively. Conclusion In Guangdong Province, the newly reported OWP cases were clustered in terms of disease stage, regional distribution, industry, enterprise scale and enterprise economic type. There was a tendency of younger age at diagnosis and shorter dust exposure duration.

A Pilot Clinical Study to Investigate the Hypomethylating Properties of Freeze-dried Black Raspberries in Patients with Myelodysplastic Syndrome or Myeloproliferative Neoplasm

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45 + cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/ MPN patients is warranted.

Application of acellular bovine pericardium patch in implant based immediate breast reconstruction / 中华外科杂志

Objective: To examine the clinical effect of acellular bovine pericardium patch in implant based immediate breast reconstruction. Methods: The clinicopathological information of 141 breast cancer patients, who admitted to Department of Breast Reconstruction and Oncoplastic Surgery, Tianjin Medical University Cancer Hospital, underwent immediate mammoplasty with implants combined with acellular bovine pericardium patches were analyzed from June 2016 to October 2019. All patients were female, with the age of (38.8±8.5) years (range: 13 to 60 years). The body mass index was (21.9±2.5) kg/m2 (range: 16.0 to 32.3 kg/m2). There were 39 cases of duct carcinoma in situ, 46 cases of stage Ⅰ, 40 cases of stage Ⅱ and 16 cases of stage Ⅲ. All patients received nipple-areola-sparing mastectomy or skin-sparing mastectomy with sentinel lymph node biopsy or axillary lymph node dissection, and prosthesis implantation with sub-pectoralis combined with breast patch. The correlation of clinicopathological characters and complications was assessed by t test, χ2 test, Fisher's exact probability method and Logistic regression. Pre-and post-operative aesthetic, quality of life scores were recorded. Results: The operation time (M(IQR)) was 3.6(1.5) hours (range: 3.0 to 6.5 hours). The early postoperative complication rate was 22.0% (31/141), prosthesis removal was the main postoperative complication, accounting for 64.5% (20/31) of the total complications, of which 15 cases occurred in the first 30 patients. The follow-up time was 28(8) months (range: 20 to 53 months), The most frequent long-term complications were capsular contracture and implant displacement, with the incidence of 11.2% (14/125) and 10.4% (13/125), respectively. Multivariate analysis showed that prosthesis volume ≥300 ml (OR=8.173, 95%CI: 1.302 to 51.315, P=0.021) and peri-areolar incision (OR=7.809, 95%CI: 2.162 to 28.211, P<0.01) were independent relative factors for the occurrence of short-term postoperative local complications. After 2 years of operation, the score of breast appearance satisfaction was 71.7±15.5, postoperative effect satisfaction was 90.4±9.5, psychological satisfaction was 90.7±17.1, sexual satisfaction was 70.1±25.1. The immediate postoperative satisfaction rate at discharge was 95.4% (134/141), and 17.6% (22/125) of patients had the intention to received revision surgery. Conclusions: Prosthesis volume ≥300 ml and peri-areolar incision were independent realtive factors for short-term local complications after bovine pericardium patch combined with prosthesis implantation in the immediate breast reconstruction. After completing the learning curve, the postoperative complications of the procedure could be decreased.

Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis / 中华预防医学杂志

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Cardiometabolic disease patterns among elderly patients with colorectal cancer in China / 中华肿瘤杂志

Objective: To explore the distribution patterns of cardiometabolic diseases (CMD) in elderly patients with colorectal cancer, and provide a reference for the prevention and treatment of cardiovascular metabolic diseases in these patients. Methods: Clinical data of 3 894 elderly patients with colorectal cancer from January 2008 to March 2018 admitted in the Chinese PLA General Hospital were recruited and the incidence rate of CMD was retrospectively analyzed. The influence factors of elderly patients with colorectal cancer combined with CMD were analyzed by multivariate Logistic regression model. Results: The morbidity rate of CMD in elderly patients with colorectal cancer is 33.4% (1 301/3 894), among them, the morbidity rate of the male was 31.9% (768/2 409), and that of the female was 35.9% (533/1 485). There was not significant difference between these two sex (P=0.074). The morbidity rates of CMD in patients of 65-74 years, 75-84 years and ≥85 years were 30.6% (754/2 462), 37.0% (479/1 294) and 49.3% (68/138), respectively, with significant differences (P<0.001). Multiple Logistic regression analysis revealed that female (OR=1.213, 95%CI: 1.056-1.394), age (75-84 years group: OR=1.344, 95%CI: 1.164-1.552; ≥85 years group: OR=2.345, 95%CI: 1.651-3.331) and body mass index (BMI 18.5-24.9 kg/m(2) group: OR=1.319, 95%CI: 1.065-1.638; ≥25 kg/m(2) group: OR=2.041, 95%CI: 1.627-2.561) were independent risk factors for elderly colorectal cancer patients with CMD. Conclusion: The morbidity rate of CMD in elderly patients with colorectal cancer increases with age and it is urgent to strengthen multidisciplinary cooperation and develop reasonable treatment plans to extend the survival and life quality of these patients.

Effect of local gene therapy on expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis in rabbits / 中华医学美学美容杂志

Objective:To investigate the effect of electroporation-mediated local gene therapy on the expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis of rabbits.Methods:The experiments were conducted in the laboratory of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from September 2019 to December 2019. Forty eight New-Zealand rabbits were randomly divided into control group (group A), gene therapy group (group B) and normal saline group (group C), with 16 rabbits in each group. After bilateral mandible osteotomy and distractors were implanted, the distractors were activated at a speed of 0.8 mm/d on 4th day, postoperatively, and lasted for 7 days, followed by consolidation period. Group A distracted only, group B was subject to local injection of recombinant plasmid pIRES-hBMP2-hVEGF165 in the distraction gap and electroporation stimulation at the beginning of activation distractors; and group C local injection of the same dose of normal saline in the distraction gap and electroporation stimulation at the beginning of activation distractors. Four animals in each group were sacrificed on the day at the end of distraction, 7th, 14th, 28th days of consolidation period, respectively. The callus in the distraction gap was taken for immunohistochemical staining and RT-PCR to detect the expression of Wnt3a and β-catenin, and image analysis was performed. SPSS 22.0 statistical software was used for data analysis.Results:Immunohistochemical staining showed that Wnt3a and β-catenin were mainly located in the cytoplasm and nuclei of fibroblasts, chondrocytes and osteoblasts in callus tissue. Immunohistochemistry and RT-PCR showed that the expression of Wnt3a and β-catenin reached a peak at the end of distraction. With the disappearance of distraction tension, the expression of Wnt3a and β-catenin gradually decreased. After gene therapy intervention, the expression of Wnt3a and β-catenin was significantly increased, and the expression of Wnt3a and β-catenin in group B was the highest at each time point, with statistically significant difference compared with groups A and C ( F=96.3, P<0.01). Conclusions:Gene therapy promotes the expression of Wnt3a and β-catenin in the callus of distraction gap, regulating the balance of the bone reconstruction system and thus promoting the formation of new bone in the distraction gap.