Research Progress on Biological Evidence Identification in Fire Scenes / 法医学杂志

Biological evidence is relatively common evidence in criminal cases,and it has strong pro-bative power because it carries DNA information for individual identification.At the scene of fire-related cases,the complex thermal environment,the escape of trapped people,the firefighting and res-cue operations,and the deliberate destruction of criminal suspects will all affect the biological evi-dence in the fire scene.Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes,and found that the blood stains,semen stains,bones,etc.are the main biological evidence which can be easily recovered with DNA in fire scenes.In order to analyze the research status and development trend of biological evidence in fire scenes,this paper systematically sorts out the relevant research,mainly including the soot removal technology,appearance method of typical biological evidence,and possibility of identifying other biological evidence.This pa-per also prospects the next step of research direction,in order to provide reference for the identifica-tion of biological evidence and improve the value of biological evidence in fire scenes.

A case analysis of medication adjustments on a moyamoya disease patient with endometriosis by DAPT treatment during perioperative period and formulation of DIE postoperative recurrence prevention / 中国临床药理学与治疗学

AIM:To explore the key points of per-sonalized treatment and medication monitoring by clinical pharmacists in the perioperative period of moyamoya disease patients with endometriosis.METHODS:This study showed a moyamoya disease patient with endometriosis who accepting dual an-tiplatelet therapy and how to adjust medication during the perioperative period.Besides,monitor-ing the use proton pump inhibitors in the perioper-ative period and the formulating a plan of DIE post-operative recurrence prevention are also our objec-tives.RESULTS:Through individualized assessment of the patient,a personalized medication adjust-ments for dual antiplatelet therapy was deter-mined.Individualized perioperative proton pump inhibitor regimen and postoperative prevention plan for endometriosis recurrence were developed.CONCLUSION:The development of individualized medication regimens and medication monitoring is the breakthrough point for clinical pharmacists to carry out pharmaceutical services.

Recent advances in radiotherapy combined with systemic treatment for breast cancer brain metastasis / 中华放射肿瘤学杂志

Breast cancer brain metastasis (BCBM) is the second most common brain metastasis cancer, which is usually characterized by multiple lesions. Radiotherapy is an important local treatment for BCBM, which includes stereotactic radiotherapy, whole brain radiotherapy (WBRT) combined with simultaneous integrated boost and WBRT (such as conformal WBRT and hippocampal avoidance - WBRT) . Meanwhile, systemic treatment of BCBM has progressed rapidly, showing a positive effect in delaying the incidence of brain metastases, maintaining asymptomatic or unprogressive brain metastases, and delaying initial or salvage local treatments. In recent years, some studies have shown that radiotherapy combined with systemic treatment for BCBM has better application prospect compared with radiotherapy alone. In this article, the radiotherapy progress of brain metastases, the role of systemic therapy in BCBM, and the clinical research of radiotherapy combined with systemic therapy were reviewed, aiming to provide some reference for clinical research in this field.

Zuoguiwan for Treating Congenital Essence Deficiency in Offspring / 中国实验方剂学杂志

Zuoguiwan， one of the classic formulas of traditional Chinese medicine （TCM）， has the effects of nourishing genuine Yin， supplementing essence， and replenishing marrow， and it is widely used in the clinical treatment of diseases caused by congenital essence deficiency. This article systematically reviewed the ancient books involving congenital deficiency and the modern research reports on the treatment of congenital deficiency with Zuoguiwan. From the formulation principle of Zuoguiwan and the TCM concept of congenital deficiency， this article discussed the theoretical basis of treating congenital deficiency with Zuoguiwan based on the modern research results. Ancient physicians have discovered that the deficiency of parents can lead to abnormal physical development and weakness of the offspring. ZHANG Jingyue divided congenital essence Qi into genuine Yin and primordial Yang and formulated Zuoguiwan based on the principle of Yin-Yang mutual assistance for supplementing congenital genuine Yin. Experimental studies have shown that Zuoguiwan can up-regulate the expression of connexin 43 （Cx43） protein and improve gap junction intercellular communication （GJIC） function to promote osteogenic differentiation and maturation of bone marrow mesenchymal stem cells and ameliorate abnormal bone development caused by congenital essence deficiency. Zuoguiwan can enhance the expression and activity of Reelin to ameliorate abnormal brain development. It can upregulate the expression of Cx43 protein to intervene in the phosphatidylinositol 3 kinase/protein kinase B （PI3K/Akt） pathway， thus repairing the reproductive functions. Zuiguiwan can promote the development and maturation of T cells and activate the Wnt/β-catenin signaling pathway in the thymus to improve immune functions. In addition， it can promote the expression of β-catenin and inhibit the expression of microtubule-associated proteins 1 light chain 3 （LC3） to attenuate skin dysfunctions. Moreover， Zuoguiwan can guide the differentiation of stem cells via the correlation between essence and vitality in TCM. Zuoguiwan has demonstrated significant therapeutic effects on some diseases in the pediatric， andrological， gynecological， geriatric， internal medicine， orthopedic and skin disease departments. On the basis of the results of experiments and clinical applications， this paper analyzes the specific connotation of congenital deficiency proposes that congenital deficiency should be subdivided into the four aspects of essence， Qi， Yin， and Yang. Congenital essence deficiency as the deficiency of genuine Yin can lead to deficiency of kidney essence in the offspring and dysfunction of kidney storing essence. Pharmacological studies have discovered that Cuscutae Semen， Lycii Fructus， and Achyranthis Bidentatae Radix in Zuoguiwan contain active components such as quercetin and kaempferol， which act on the targets such as recombinant prostaglandin endoperoxide synthase 2 （PTGS2）， interleukin-6 （IL-6）， mitogen-activated protein kinases （MAPK14）， tumor necrosis factor （TNF）， TP53， Vascular permeability factor A （VEGFA）， and albumin （ALB） to play a role in reproductive system development and hormone responses. Zuoguiwan has unique advantages over Liuwei Dihuangwan in nourishing congenital genuine Yin in the kidney and can achieve better therapeutic effects on the syndromes and diseases caused by congenital essence deficiency. This review is expected to enrich the knowledge about the efficacy and clinical application of Zuoguiwan， provide new perspectives and methods for the prevention and treatment of congenital deficiency and congenital essence deficiency， and give insights into the application of Zuoguiwan in modern healthcare， especially in the nurturing of offspring.

Effects of single-person hyperbaric chamber on hemodynamics of superior mesenteric artery in personnel rushing to extremely high altitude area / 医疗卫生装备

Objective To evaluate the effect of the single-person hyperbaric chamber on hemodynamics of superior mesenteric artery in the personnel rushing to the extremely high altitude area.Methods Sixty healthy young male subjects who traveled by car from the plains(890 m above sea level)to a very high altitude area(5 130 m above sea level)were randomly divided into a control group,a low-flow oxygen therapy group and a hyperbaric oxygen group,with 20 cases in each group.After entering the plateau area,no intervention was made in the control group;in the low-flow oxygen therapy group,low-flow oxygen therapy was performed once a day by means of nasal oxygen cannula(oxygen flow rate of 2 L/min,60 min/times);in the hyperbaric oxygen group,hyperbaric oxygen therapy was carried out once a day in a single-person hyperbaric oxygen chamber(pressuri-zation pressure of 0.25 MPa,60 min/times).The subjects in the three groups had their peak systolic velocity(PSV),resistance index(RI),and pulsation index(PI)of the main trunks of the SMAs and their grade 1 and 2 branches measured and compared using color Doppler ultrasound diagnostic instruments on days 30,60,and 90,respectively,after acute entry to the plateau.SPSS 19.0 software was used for statistical analysis.Results There were no significant differences in PSV,RI and PI of SMA and its 1 st and 2nd grade branches between the 3 groups 30 days after entry(P＞0.05).Sixty days after entry,the control group had the values of PSV statistically higher than those of the other two groups(P＜0.05);there were no significant differences between the low-flow oxygen therapy group and the hyperbaric oxygen group in the values of PSV(P＞0.05);the three groups had no obvious differences in the values of RI and PI(P＞0.05).Ninety days after entry,the control group had the values of PSV,RI and PI all significantly higher than those of the other two groups(P＜0.05);the low-flow oxygen therapy group had the values of PSV statistically higher than those of the hyperbaric oxygen group(P＜0.05),while the values of RI and PI not significantly different from those of the hyperbaric oxygen group(P＞0.05).Conclusion Single-person hyperbaric oxygen chamber significantly improves the SMA blood flow changes due to oxygen partial pressure reduction in the plateau,and thus is of significance for preventing ischemic enteropathy of the personnel rushing to the plateau.[Chinese Medical Equipment Journal,2023,44(10):59-63]

Clinical analysis of 11 cases with pancreatic metastatic tumor diagnosed by endoscopic ultrasound-guided fine-needle aspiration / 中华胰腺病杂志

Objective:To analyze the characteristics of pancreatic metastatic tumors and evaluate the clinical value of endoscopic ultrasound-guided fine-needle aspiration or biopsy (EUS-FNA/B) in their diagnosis.Methods:A retrospective analysis was conducted on clinical, radiological, and pathological data of 11 cases with pancreatic metastatic tumors diagnosed by EUS-FNA/B at the First Affiliated Hospital of Naval Medical University between January 2011 and December 2020. Tumor size, number of lesions, time interval between diagnosis of metastatic lesions and primary tumors, radiological and EUS findings and pathological types were recorded, and success rate and diagnostic rate of EUS-FNA/B were analyzed.Results:The 11 patients with pancreatic metastatic tumors had an age range of 43 to 76 years, including 7 males and 4 females. Eight cases presented with symptoms of abdominal pain and poor appetite, 1 case had cervical lymph node enlargement, and 2 cases were detected during routine physical examination. Five cases had abnormal serum tumor markers. All patients had a confirmed history of primary tumors, and the median time interval between diagnosis of pancreatic metastatic lesions and primary tumors was 24 months (-1-124 months). Seven cases had solitary lesions, and 4 cases had multiple nodules under EUS. Eight cases were initially diagnosed clinically as pancreatic lesions or tumor, while 3 cases were considered as pancreatic metastatic tumor. All of 11 cases underwent EUS-FNA/B and were histologically confirmed as pancreatic metastatic tumors. The most common pathological type was lung small cell neuroendocrine cancer ( n=4), followed by renal cell carcinoma ( n=3), and esophageal squamous cell carcinoma ( n=1), pulmonary squamous cell carcinoma( n=1), malignant melanoma ( n=1), and gastric adenocarcinoma ( n=1). Conclusions:The pancreas is not a common target site for tumor metastasis.EUS-FNA/B is a relatively safe minimally invasive method for the diagnosis of pancreatic metastatic tumors.

Improvement of quality standard of Xiaojin capsules / 中国药师

Objective To improve the quality standard of Xiaojin capsules.Methods The agents content of acetyl-11-keto-β-bos wellic acid in Vinegar frankincense was determined by HPLC.According to GC detection patterns of 15 batches of samples,the similarity evaluation was conducted by using the"similarity evaluation system for chromatographic fingerprint of TCM(2012 edition)"of National Pharmacopoeia Committee to confirm common peaks.According to the Chinese Pharmacopoeia method,the contents of Pb,Cd,Cu,As and Hg in samples were detected.Results The linear range of acetyl-11-keto-β-boswellic acid was 13.346-166.824 μg·ml-1(r=0.999 8).The method which possesses high accuracy,and strong specificity,repeatability is good,and the average recovery was 100.76％with an RSD of 1.52％(n=6).The GC fingerprint detection method of Xiaojin capsules was established,and 11 common peaks were identified.The similarity of 15 batches of samples was greater than 0.870,indicating a good similarity.The contents of Pb,Cd,Cu,As and Hg in 15 batches of samples are in accordance with the reference limits in Chinese Pharmacopoeia.Conclusion The GC fingerprint detection method and the HPLC method for the determination of 11-carbonyl-β-acetylboswellic acid,as well as the examination of heavy metals,it can be used as a quality control item for the enhancement of the quality control standards of Xiaojin capsules.

A randomized controlled study of balloon compression-assisted endoscopic injection sclerotherapy versus traditional endoscopic injection sclerotherapy for esophageal varices / 中华消化内镜杂志

Objective:To evaluate balloon compression-assisted endoscopic injection sclerotherapy (bc-EIS) for the treatment of esophageal varices.Methods:From June 2019 to November 2020, cirrhotic patients with esophageal varices who received endoscopic injection sclerotherapy (EIS) in the First Affiliated Hospital of Anhui Medical University were enrolled in the study. The patients were randomly divided into the bc-EIS group and the traditional EIS group. The number of treatments to eradicate varicose veins, the dose of sclerosing agent used in the first treatment, the number of injection points in the first treatment, the rebleeding rate within 10 months after the operation and the incidence of complications or adverse reactions were compared between the two groups.Results:Ninety-two cases were initially included in the study, and 7 cases were excluded based on exclusion criteria. Finally, 85 cases were included in the data analysis, 47 in the bc-EIS group and 38 in the traditional EIS group. The first eradication rate, the second cumulative eradication rate and the third cumulative eradication rate were 82.98% (39/47), 91.49% (43/47) and 100.00% (47/47) in the bc-EIS group, and they were 10.53% (4/38) ( χ 2=44.125, P<0.001), 31.58% (12/38) ( χ 2=33.023, P<0.001) and 63.16% (24/38) ( χ 2=20.730, P<0.001), respectively in the traditional EIS group, and the differences were statistically significant. The treatment times of eradicating varicose veins in the bc-EIS group and the traditional EIS group were 1.25±0.60 and 3.21±1.41, respectively, with significant difference. The dosage of sclerosing agent in first treatment in the bc-EIS group and the traditional EIS group was 17.66±7.14 mL and 22.92±6.84 mL, respectively ( t=3.441, P=0.001). The numbers of initial injection points in the bc-EIS group and the traditional EIS group were 2.70±0.86 and 2.78±1.04, respectively and the difference was not statistically significant ( t=1.847, P=0.065). The rebleeding rates of the two groups within 10 months after the operation were 2.13% (1/47) and 18.42% (7/38) respectively ( χ 2=4.771, P=0.029). There were no serious complications in the two groups. The incidences of retrosternal pain, nausea and vomiting, abdominal distension and ulcer were 2.13% (1/47), 2.13% (1/47), 4.26% (2/47) and 0.00% (0/47) in the bc-EIS group, and in the traditional EIS group, they were 5.26% (2/38) ( χ 2=0.035, P=0.851), 5.26% (2/38) ( χ 2=0.035, P=0.851), 7.89% (3/38) ( χ 2=0.060, P=0.806) and 7.89% (3/38) ( χ 2=1.877, P=0.171), respectively, without significant difference. Conclusion:Bc-EIS is more effective than traditional EIS for the treatment of esophageal varices with lower postoperative rebleeding rate, which shows better clinical application value.

Detection of early gastric cancer in white light imagings based on region-based convolutional neural networks / 安徽医科大学学报

Objective @#To develop an endoscopic automatic detection system in early gastric cancer (EGC) based on a region-based convolutional neural network ( Mask R-CNN) ．@*Methods @# A total of 3 579 and 892 white light images (WLI) of EGC were obtained from the First Affiliated Hospital of Anhui Medical University for training and testing，respectively．Then，10 WLI videos were obtained prospectively to test dynamic performance of the RCNN system．In addition，400 WLI images were randomly selected for comparison with the Mask R-CNN system and endoscopists．Diagnostic ability was assessed by accuracy，sensitivity，specificity，positive predictive value ( PPV) ， and negative predictive value (NPV) . @*Results @# The accuracy，sensitivity and specificity of the Mask R-CNN system in diagnosing EGC in WLI images were 90. 25% ，91. 06% and 89. 01% ，respectively，and there was no significant statistical difference with the results of pathological diagnosis．Among WLI real-time videos，the diagnostic accuracy was 90. 27%．The speed of test videos was up to 35 frames / s in real time．In the controlled experiment， the sensitivity of Maks R-CNN system was higher than that of the experts (93. 00% vs 80. 20% ，χ2 = 7. 059，P < 0. 001) ，and the specificity was higher than that of the juniors (82. 67% vs 71. 87% ，χ2 = 9. 955，P＜0. 001) ， and the overall accuracy rate was higher than that of the seniors (85. 25% vs 78. 00% ，χ2 = 7. 009，P＜0. 001) . @*Conclusion@#The Mask R-CNN system has excellent performance for detection of EGC under WLI，which has great potential for practical clinical application.

Predictive value of multimodal magnetic resonance imaging based radiomics model for micro-satellite instability of rectal cancer / 中华消化外科杂志

Objective:To investigate the predictive value of multimodal magnetic resonance imaging (MRI) based radiomics model for microsatellite instability (MSI) of rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 117 patients with rectal cancer who were admitted to 2 medical centers, including 74 in Ningbo Urology & Nephrology Hospital and 43 in the First Affiliated Hospital of Zhejiang University School of Medicine, from January 2020 to December 2022 were collected. There were 73 males and 44 females, aged (63±5)years. Based on random number table, all 117 patients were divided into the training dataset of 70 cases and the test dataset of 47 cases with a ratio of 7:3. All patients underwent pelvic MRI exami-nation. Observation indicators: (1) construction of radiomics prediction model and analysis of charac-teristics; (2) analysis of factors influencing MSI of rectal cancer in the training dataset; (3) construc-tion and evaluation of the prediction model for MSI of rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted using the one way ANOVA and multivariate analysis was conducted using the Logistic regression model with forward method. The receiver operating characteristic curve was drawn, and the area under the curve (AUC), decision curve, calibration curve and Delong test were used to evaluate the predictive ability of prediction model. Results:(1) Construction of radiomics prediction model and analysis of characteristics. Five thousand five hundred and eighty radiomics features were finally extracted from the 117 patients. Based on the feature selection using the maximum correlation minimum redundancy method, and the least absolute shrinkage and selection operator fitting algorithm, 9 radiomics features were finally selected. The radiomics prediction model was constructed based on calculation of the radiomics score. (2) Analysis of factors influencing MSI of rectal cancer in the training dataset. Results of multivariate analysis showed that platelet count was an independent influencing factor for MSI of rectal cancer [ odds ratio=1.13, 95% confidence interval ( CI) as 1.06-1.21, P<0.05]. (3) Construction and evaluation of the prediction model for MSI of rectal cancer. The clinical prediction model and clinical-radiomics combined prediction model were constructed based on the results of multivariate analysis. The AUC of clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model in the training dataset was 0.94 (95% CI as 0.86-0.98), 0.96 (95% CI as 0.88-0.99), 0.99 (95% CI as 0.93-1.00), respectively, with the sensitivity and specificity as 90.7%, 91.2%, 96.9% and 85.0%, 88.9%, 94.3%. Results of Delong test showed that there was a significant difference in the predictive performance between the clinical-radiomics combined prediction model and the clinical prediction model ( Z=2.20, P<0.05), and there was no significant difference between the radiomics prediction model and the clinical-radiomics combined prediction model or the clinical prediction model ( Z=1.94, 0.60, P>0.05). The AUC of clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model in the test dataset was 0.97 (95% CI as 0.88-1.00), 0.86 (95% CI as 0.73-0.95), 0.97(95% CI as 0.87-1.00), respectively, with the sensitivity and specificity as 99.3%, 95.8%, 99.3% and 85.7%, 73.9%, 90.5%. Results of Delong test showed that there was a significant difference in the predictive performance between the clinical-radiomics combined prediction model and the radiomics prediction model ( Z=2.21, P<0.05), and there was no significant difference between the clinical prediction model and the clinical-radiomics combined prediction model or the radiomics prediction model ( Z=0.17, 1.82, P>0.05). Results of calibration curve showed that clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model had good ability in predicting the MSI status of rectal cancer. Results of decision curve showed that compared to clinical prediction model and radiomics prediction model, clinical-radiomics combined prediction model had greatest net gain in predicting the MSI of rectal cancer. Conclusion:The prediction model based on 9 radiomics features after selecting can effectively predict the MSI status of rectal cancer, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Immunotherapy in the neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中华放射肿瘤学杂志

Long-course concurrent chemoradiotherapy (CCRT) or short-course radiotherapy (SCRT) prior to surgery and postoperative chemotherapy is one of the main standard therapies for patients with locally advanced rectal cancer (LARC). On this basis, total neoadjuvant therapy (TNT) has been shown to improve disease-free survival, distant metastasis-free survival and complete response rates, whereas the 3-year distant recurrence rate is still above 20% and pathological complete response (pCR) is less than 30%. Long-term survival and adverse reactions remain to be improved. Currently, significant achivement has been obtained in immunotherapy. Application of immunotherapy in the treatment of rectal cancer remains to be urgently validated. In recent years, immunotherapy combined with preoperative chemoradiotherapy has been adopted for LARC in clinical trials. Besides, immunotherapy alone, especially programmed death-1 (PD-1) / programmed death ligand-1 (PD-L1) inhibitor, has also been utilized to treat colon rectal cancer. Relevant research progress was reviewed in this article.

Management practice of Investigator-Initiated Trials in the new period / 中华医学科研管理杂志

Objective:In the context of China′s increasing standardized management requirements of clinical research, this article aims to explore the management methods of investigator-initiated trials in the new period, to provide possible reference for other medical institutions dedicated to clinical research.Methods:According to the requirements set forth by the＂Administrative Measures for Investigator-Initiated Trials in Medical and Health Institutions (Trial)", combined with the hospital management practice, experiences regarding the research management system construction and implementation, management system construction and its implementation effects are summarized and analyzed.Results:By exploring and summarizing the connotation of high-quality clinical research under the New Policy, tailored clinical research management system in our hospital was developed and implemented. And the hospital′s clinical research capability and level have been greatly improved, which enhancing the hospital academic influence, as well as its competence for serving the development of national and regional clinical research.Conclusions:Along with the rapid progress of clinical research, hospitals need to assure the compliance of national laws and regulations, and develop appropriate and applicable institutional management measures to empower the conduct of high quality clinical research.

Simultaneous detection of 7 important Rickettsiales pathogens by TaqMan-probe quantitative real-time PCR / 中华流行病学杂志

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.

Comparison on blood-prostate barrier permeability of tanshinone extract and corresponding major monomers / 中国中药杂志

In this study, the transmittance of tanshinone Ⅱ_A(Tan Ⅱ_A) and cryptotanshinone(CTS) through the blood-prostate barrier and their distributions in the prostate tissue were compared between tanshinone extract(Tan E) treatment group and the corresponding monomer composition group under the equivalent dose conversion in vitro and in vivo. First, the human prostate epithelial cell line RWPE-1 was cultured in vitro for 21 days for the establishment of a blood-prostate barrier model, and the transmission of Tan Ⅱ_A and CTS through the barrier model was investigated after administration of Tan E and corresponding single active components. Second, SD rats were administrated with 700 mg·kg~(-1) Tan E, 29 mg·kg~(-1) CTS, and 50 mg·kg~(-1) Tan Ⅱ_A by gavage, and plasma and prostate tissue samples were collected at the time points of 2, 4, 8, 12, and 24 h. The Tan Ⅱ_A and CTS concentrations in the samples were determined. The results showed that in the cell model, the cumulative transmission amounts of CTS and Tan Ⅱ_A in the extract at each time point were higher than those of the corresponding single active components(P<0.01). In rats, after the administration of Tan E, the concentrations of Tan Ⅱ_A and CTS in rat plasma and prostate were higher than those of the corresponding single active components. This study demonstrated that the coexisting components in Tan E promoted the penetration of its main pharmacological components Tan Ⅱ_A and CTS through the blood-prostate barrier. The findings provide a theoretical and experimental basis for the application of Tan E in the clinical treatment of prostate-related diseases.

Research progress on the relation and related mechanism of night shift work and cardiovascular disease / 中华劳动卫生职业病杂志

Cardiovascular disease is a class of diseases involving the heart or blood vessels, which accounts for about one-third of all deaths worldwide each year. Unhealthy diet, lack of physical activity, smoking and excessive alcohol consumption are all risk factors for cardiovascular disease. With the increasing number of night shift workers, the number of patients with cardiovascular disease has increased, and night shift work has gradually become a risk factor of cardiovascular disease. At present, the mechanism of cardiovascular disease caused by night shift work is still unclear. This review summarizes the relationship between night shift work and cardiovascular disease and its related biochemical indicators, and discusses the research on related mechanisms.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

Risk predictors of pulmonary tuberculosis in patients with chronic kidney disease / 公共卫生与预防医学

Objective The risk prediction factors of patients with chronic kidney disease (CKD) complicated with pulmonary tuberculosis were analyzed, and the risk prediction model was constructed to provide theoretical basis for the prevention and treatment of pulmonary tuberculosis in patients with CKD. Methods Stratified sampling was used to randomly select 289 patients with CKD admitted to our hospital as the investigation objects. According to whether patients complicated with tuberculosis, they were divided into experimental group (n=65, CKD complicated with tuberculosis) and control group (n=224, CKD). Univariate analysis and logistic regression were used to analyze the influencing factors of pulmonary tuberculosis in PATIENTS with CKD. According to the regression results, the risk prediction model of pulmonary tuberculosis in CKD patients was established, and the ROC curve was used to predict the efficacy of the model. Results Among 289 patients with CKD, 65 cases (22.49%) had pulmonary tuberculosis. Chest X-ray showed 54 cases of infiltrating pulmonary tuberculosis, 5 cases of voiding pulmonary tuberculosis, 4 cases of caseous pneumonia and 2 cases of tuberculous pleurisy. The main clinical manifestations of CKD complicated with pulmonary tuberculosis were low fever, poor appetite and fatigue in 36 cases, cough and expectoration in 18 cases, high fever in 9 cases and pleural effusion in 2 cases. Mycobacterium tuberculosis culture was positive in 23 cases (35.38%). There were no significant differences in age, CKD stage, past tuberculosis history, low immunity, malnutrition, dialysis treatment, anemia and hypoproteinemia between 2 groups (P-(0.496+0.839×(low immunity)+ 0.892×(malnutrition)+ 1.247×(dialysis)]; ROC curve was used to analyze the predictive efficacy of the regression model. The results showed that the AUC of pulmonary tuberculosis predicted by the risk prediction model was 0.779, 95%Cl(0.668-0.889) for CKD patients. Conclusion The risk of tuberculosis in CKD is higher,low immunity, malnutrition, dialysis treatment of CKD patients is high risk for tuberculosis, according to the specific situation of the patients, take targeted measures to prevention, can reduce the risk of tuberculosis in patients with CKD.

Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes

Background@#Dysfunction of vascular endothelial cells (ECs) plays a central role in the pathogenesis of cardiovascular complications in diabetes. SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 5 (SMARCA5) is a key regulator of chromatin structure and DNA repair, but its role in ECs remains surprisingly unexplored. The current study was designed to elucidate the regulated expression and function of SMARCA5 in diabetic ECs. @*Methods@#SMARCA5 expression was evaluated in ECs from diabetic mouse and human circulating CD34+ cells using quantitative reverse transcription polymerase chain reaction and Western blot. Effects of SMARCA5 manipulation on ECs function were evaluated using cell migration, in vitro tube formation and in vivo wound healing assays. Interaction among oxidative stress, SMARCA5 and transcriptional reprogramming was elucidated using luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation. @*Results@#Endothelial SMARCA5 expression was significantly decreased in diabetic rodents and humans. Hyperglycemia-suppressed SMARCA5 impaired EC migration and tube formation in vitro, and blunted vasculogenesis in vivo. Contrarily, overexpression of SMARCA5 in situ by a SMARCA5 adenovirus-incorporated hydrogel effectively promoted the rate of wound healing in a dorsal skin punch injury model of diabetic mice. Mechanistically, hyperglycemia-elicited oxidative stress suppressed SMARCA5 transactivation in a signal transducer and activator of transcription 3 (STAT3)-dependent manner. Moreover, SMARCA5 maintained transcriptional homeostasis of several pro-angiogenic factors through both direct and indirect chromatin-remodeling mechanisms. In contrast, depletion of SMARCA5 disrupted transcriptional homeostasis to render ECs unresponsive to established angiogenic factors, which ultimately resulted in endothelial dysfunction in diabetes. @*Conclusion@#Suppression of endothelial SMARCA5 contributes to, at least in part, multiple aspects of endothelial dysfunction, which may thereby exacerbate cardiovascular complications in diabetes.

The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.