To summarize the clinical experience of Professor LIU Jinmin in treatment for epilepsy. It is believed that main pathogenesis of epilepsy is yangming failure to close and vital activity loss control， so a therapeutic approach focused on restoring the closure of yangming and regaining vital activity was proposed for the treatment of epilepsy. For excess syndrome， the treatment focuses on draining excess and descending qi， promoting purgation and restoring spirit. When yangming dryness-heat predominates， the approach involves unblock the bowels and regulating the spirit， descending qi and reducing fire， with modified Chengqi Decoction （承气汤） as prescription； when yangming phlegm-fire predominates， the treatment focuses on clearing heat and resolving phlegm， calming mind and suppressing fright， with modified Qingxin Wendan Decoction （清心温胆汤） as prescription； when yangming blood stasis predominates， the approach involves breaking up blood stasis and promoting purgation， eliminating stasis and awakening the mind， with Taoren Chengqi Decoction （桃核承气汤） as prescription. For deficiency syndrome， the treatment emphasizes tonifying deficiency and raising qi， strengthening the stomach and nourishing the spirit. When center qi deficiency and sinking of clear qi of the nutrients from food， the approach involves replenishing and uplifting qi while nourishing vital activity， with modified Liujunzi Decoction （六君子汤） as prescription； when yin deficiency and fluid consumption， the treatment focuses on nourishing stomach and tonifying yin， promoting fluid production and calming the spirit， with modified Maimendong Decoction （麦门冬汤） combined with Yiwei Decoction （益胃汤） as prescriptions. In clinical situations of deficiency-excess complex， it is essential to distinguish the primary condition from the secondary， applying both supplementing and draining methods flexibly to achieve optimal treatment.

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) in a geriatric emergency ward, and to provide references for the prevention and control of multidrug-resistant bacteria in a hospital in Shanghai. MethodsOn-site epidemiological investigation, combined with environmental hygiene monitoring and pulsed field gel electrophoresis (PFGE) molecular typing method, were adopted to investigate a suspected outbreak of CRKP infection in the geriatric emergency ward of a hospital from October to November 2022, aiming at finding out factors caused the outbreak before taking corresponding control measures. ResultsA total of 3 cases of healthcare-associated CRKP infection were identified, of which 2 cases were homologous to a previous case of community-associated CRKP infection. What’s more, the 2 cases lived in the same ward with the latter and with adjacent beds, but the third case was non-homologous to the community-associated infection case. A total of 46 samples were collected from the environmental surfaces and the hands of healthcare workers, of which 7 samples tested positive for CRKP and were identical to the strains from the 2 healthcare-associated infection cases and the 1 community-associated infection case, originating from the bedrails, bedside tables, surface of non-invasive ventilator, bed curtains and panels of monitoring equipment, with a detection rate of 15.22%. But none of the 11 samples from the hands of healthcare workers tested positive for CRKP. The outbreak was effectively controlled after taking specific prevention and control measures such as strengthening personnel management, intensifying environmental cleaning and disinfection and strictly enforcing hand hygiene among healthcare workers. Subsequently, no similar new cases were reported during the 14-day follow-up period. ConclusionIncomplete environmental cleaning and disinfection, as well as inadequate enforcement of hand hygiene among heatheare workers may have contributed to the suspected outbreak of CRKP in the geriatric emergency ward. Early warning and timely investigation of suspected outbreaks of multidrug-resistant bacteria are crucial for preventing and controlling such outbreaks in hospitals.

ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease （GERD） based on literature， providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis （RE）， nonerosive reflux disease （NERD） and Barrett's esophagus （BE） model construction from January 1， 2014 to January 27， 2024， were retrieved from databases such as CNKI， Wanfang， VIP， Web of Science， and Pubmed. Information on animal strains， genders， modeling methods including disease-syndrome combination models， modeling cycles were extracted； for studies with model evaluation， the methods of model evaluation were also extracted； then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE （88/148， 59.46%） and NERD （9/14， 64.29%）. For BE， C57BL/6 mice were most commonly used （11/20， 55.00%）. Male animals （RE： 111/135， 82.22%； NERD： 11/14， 78.57%； BE： 10/12， 83.33%） were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer， gastric content reflux， or mixed reflux， among which forestomach ligation + incomplete pylorus ligation （42/158， 26.58%） was the most common modeling method； the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa， visceral hypersensitivity， and emotional problems， and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus （8/14， 57.14%） was the most common modeling method； the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux， and constructing interleukin 2-interleukin 1β transgenic mice （7/25， 28.00%） was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE， NERD， and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics （e.g.， RE focusing on structural damage， NERD emphasizing visceral hypersensitivity）. Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches （e.g.， composite etiology simulation） and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.

Breast cancer remains a leading cause of mortality in women worldwide.Triple-negative breast cancer(TNBC)is a particularly aggressive subtype characterized by rapid progression,poor prognosis,and lack of clear therapeutic targets.In the clinic,delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges.Within the scope of our study,high hetero-geneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples.Notably,TNBC exhibited significant specificity regarding cell prolif-eration,differentiation,and disease progression.Significant associations between tumor grade,prog-nosis,and TNBC oncogenes were established via pseudotime trajectory analysis.Consequently,we further performed comprehensive characterization of the TNBC microenvironment.A crucial epithelial subcluster,E8,was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC.Additionally,epithelial-mesenchymal transition(EMT)-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions,contributing to tumor growth.Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC.The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs,such as pelitinib.We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model.Overall,our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.

Objective To compare the efficacy of endoscopic bougie/balloon dilation(EBD),endoscopic radial incision(ERI),and ERI combined with esophageal stent placement(ESP)for the treatment of benign esophageal stenosis,and evaluate the feasibility and safety of ERI combined with ESP for the treatment of benign esophageal stenosis.Methods 48 Patients with benign esophageal stenosis from January 2019 to January 2023 were recruited,and divided into EBD group(n=24),ERI group(n=17)and ERI+ESP group(n=7).The differences in operating success,restenosis and complications among the three groups were compared.Results The number of previous endoscopic treatment in ERI+ESP group was more than that in EBD group and ERI group,and the differences were statistically significant(P＜0.05).Technical success was achieved in 23 cases and clinical remission in 23 cases in EBD group,technical success in 16 cases and clinical remission in 15 cases in ERI group,technical success in 7 cases and clinical remission in 7 cases in ERI+ESP group.There was no significant difference in technical success rate and clinical remission rate among the three groups(P＞0.05).After 3 months of follow-up,there were 15,9 and 1 cases of esophageal restenosis in the EBD group,ERI group and ERI+ESP group,respectively.There was no significant difference in the rate of esophageal restenosis among the 3 groups(P＞0.05).After 6 months of follow-up,there were 20 cases of esophageal restenosis in the EBD group,13 cases in the ERI group and 1 case in the ERI+ESP group.The rate of esophageal restenosis in the ERI+ESP group was significantly lower than that in the EBD group and the ERI group(P＜0.05).However,there was no statistically significant difference in the esophageal restenosis rate between the EBD group and the ERI group(P＞0.05).The time to the first postoperative restenosis was 74.00(48.75,159.00)days in the EBD group,84.00(54.50,195.00)days in the ERI group,and 250.00(206.00,289.00)days in the ERI+ESP group.The time to the first postoperative restenosis was longer in the ERI+ESP group than that in the EBD and ERI groups.The differences were statistically significant(P＜0.05),but there was no significant difference in restenosis time between EBD group and ERI group(P＞0.05).There were 5,5 and 3 cases of complications in the EBD group,ERI group and ERI+ESP group,respectively,and there was no significant difference in the incidence of complications among the three groups(P＞0.05).Conclusion ERI+ESP is comparable to EBD and ERI in terms of technical success and short-term clinical remission rate for the treatment of benign esophageal stenosis,and is superior to EBD and ERI in terms of long-term restenosis rate and restenosis time,with no influence on the occurrence of complications.

Objective To investigate the value of magnetic resonance imaging-proton density fat fraction(MRI-PDFF)in evaluating hepatic steatosis in patients with chronic hepatitis B virus(HBV)infection.Methods The patients,aged>16 years,who visited the outpatient service or were hospitalized in Beijing Tsinghua Changgung Hospital from January 2018 to December 2022 and were diagnosed with chronic HBV infection were enrolled,and all patients underwent MRI examination of the liver in our hospital.The patients were divided into groups based on the presence or absence of liver cirrhosis,and the consistency in PDFF between different hepatic segments was compared between groups.The Kappa consistency test and intraclass correlation coefficient(ICC)were used for consistency analysis.Results A total of 76 patients treated with nucleoside analogues were enrolled,among whom 23(30.26％)had liver cirrhosis.For all patients,the simple arithmetic average of PDFF fluctuated between 1.49％and 30.93％.According to MRI-PDFF≥5％as the diagnostic criterion for fatty liver disease,there were 29 patients(38.16％)with fatty liver disease among all patients.For all 76 patients,the simple arithmetic average of PDFF was lower than the weighted average of PDFF for the whole liver,and there was no significant difference between the simple arithmetic average of PDFF,the weighted average of PDFF,and the PDFF values of the left and right lobes of the liver(F=0.39,P=0.76).The consistency test showed that the PDFF values of each hepatic segment and the left and right lobes of the liver had strong consistency with the weighted average and simple arithmetic average of PDFF,with an ICC of>0.75,but the consistency between the PDFF value of the right lobe and the weighted average of PDFF was higher than that between the PDFF value of the left lobe and the weighted average of PDFF.In the consistency test of differentiating fatty liver disease in patients with liver cirrhosis,there was poor consistency between the PDFF value of segment Ⅶ and the weighted average of PDFF(Kappa=0.39),with moderate consistency for the left lobe and the Ⅰ,Ⅱ,Ⅲ,Ⅴ,Ⅵ,and Ⅷ segments.For the patients with liver cirrhosis,the lowest consistency was observed between the PDFF value of Ⅶ segment and the weighted average of PDFF for the whole liver,and the highest consistency was observed between the PDFF value of Ⅵ segment and the weighted average of PDFF for the whole liver.For the patients without liver cirrhosis,the lowest consistency was observed between the PDFF value of Ⅱ segment and the weighted average of PDFF for the whole liver,and the highest consistency was observed between the PDFF value of Ⅴ segment and the weighted average of PDFF for the whole liver.Conclusion MRI-PDFF is more comprehensive in evaluating hepatic steatosis in patients with chronic HBV infection,and for the patients with liver cirrhosis,there is poor consistency between the PDFF value of each segment and the weighted average of PDFF.

Background::Radiation (IR)-induced DNA damage triggers cell cycle arrest and has a suppressive effect on the tumor microenvironment (TME). Wee1, a cell cycle regulator, can eliminate G2/M arrest by phosphorylating cyclin-dependent kinase 1 (CDK1). Meanwhile, programed death-1/programed death ligand-1 (PD-1/PDL-1) blockade is closely related to TME. This study aims to investigate the effects and mechanisms of Wee1 inhibitor AZD1775 and anti-PD-1 antibody (anti-PD-1 Ab) on radiosensitization of hepatoma.Methods::The anti-tumor activity of AZD1775 and IR was determined by 3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide (MTT) assay on human and mouse hepatoma cells HepG2, Hepa1-6, and H22. The anti-hepatoma mechanism of AZD1775 and IR revealed by flow cytometry and Western blot in vitro. A hepatoma subcutaneous xenograft mice model was constructed on Balb/c mice, which were divided into control group, IR group, AZD1775 group, IR + AZD1775 group, IR + anti-PD-1 Ab group, and the IR + AZD1775 + anti-PD-1 Ab group. Cytotoxic CD8 + T cells in TME were analyzed by flow cytometry. Results::Combining IR with AZD1775 synergistically reduced the viability of hepatoma cells in vitro. AZD1775 exhibited antitumor effects by decreasing CDK1 phosphorylation to reverse the IR-induced G2/M arrest and increasing IR-induced DNA damage. AZD1775 treatment also reduced the proportion of PD-1 +/CD8 + T cells in the spleen of hepatoma subcutaneous xenograft mice. Further studies revealed that AZD1775 and anti-PD-1 Ab could enhance the radiosensitivity of hepatoma by enhancing the levels of interferon γ (IFNγ) + or Ki67 + CD8 T cells and decreasing the levels of CD8 + Tregs cells in the tumor and spleen of the hepatoma mice model, indicating that the improvement of TME was manifested by increasing the cytotoxic factor IFNγ expression, enhancing CD8 + T cells proliferation, and weakening CD8 + T cells depletion. Conclusions::This work suggests that AZD1775 and anti-PD-1 Ab synergistically sensitize hepatoma to radiotherapy by enhancing IR-induced DNA damage and improving cytotoxic CD8 + T cells in TME.

Objective To evaluate the application of three deep learning algorithms in automatic segmentation of clinical target volumes (CTVs) in high-dose-rate brachytherapy after surgery for endometrial carcinoma. Methods A dataset comprising computed tomography scans from 306 post-surgery patients with endometrial carcinoma was divided into three subsets: 246 cases for training, 30 cases for validation, and 30 cases for testing. Three deep convolutional neural network models, 3D U-Net, 3D Res U-Net, and V-Net, were compared for CTV segmentation. Several commonly used quantitative metrics were employed, i.e., Dice similarity coefficient, Hausdorff distance, 95th percentile of Hausdorff distance, and Intersection over Union. Results During the testing phase, CTV segmentation with 3D U-Net, 3D Res U-Net, and V-Net showed a mean Dice similarity coefficient of 0.90 ± 0.07, 0.95 ± 0.06, and 0.95 ± 0.06, a mean Hausdorff distance of 2.51 ± 1.70, 0.96 ± 1.01, and 0.98 ± 0.95 mm, a mean 95th percentile of Hausdorff distance of 1.33 ± 1.02, 0.65 ± 0.91, and 0.40 ± 0.72 mm, and a mean Intersection over Union of 0.85 ± 0.11, 0.91 ± 0.09, and 0.92 ± 0.09, respectively. Segmentation based on V-Net was similarly to that performed by experienced radiation oncologists. The CTV segmentation time was < 3.2 s, which could save the work time of clinicians. Conclusion V-Net is better than other models in CTV segmentation as indicated by quantitative metrics and clinician assessment. Additionally, the method is highly consistent with the ground truth, reducing inter-doctor variability and treatment time.

Abstract Incomplete combustion of solid fuels produces a large amount of pollutants, which are associated with the incidence and mortality risks of various chronic diseases, making it one of the significant environmental and public health issues in China. Studies have shown that air pollutants generated by the use of solid fuels in households may increase the risk of diabetes by interfering with glucose metabolism and altering insulin resistance, and may also increase the risk of hypertension by inducing vascular oxidative stress and inflammatory responses. This article reviews relevant literature published domestically and internationally from 2001 to 2024, focusing on the impacts of household solid fuel use on diabetes and hypertension, as well as suggestions for reducing household solid fuel use, providing the reference for the prevention of related chronic diseases.

Objective: To evaluate the risk of fine particulate matter (PM2.5) on excess mortality among residents. Methods: The data of residential mortality in Yangzhou City, Jiangsu Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System. The average daily mass concentration of PM2.5 and meteorology data were collected from the Yangzhou Environmental Monitoring Station and Yangzhou Meteorological Bureau, respectively. The effects of PM2.5 on non-accidental mortality, morality of respiratory diseases and mortality of circulatory diseases were evaluated using a generalized additive model. The risk of excess mortality was evaluated using excess risk (ER) and the number of excess mortality. Results: The median average annual mass concentration of PM2.5 was 38.00 (interquartile range, 31.95) µg/m3 in Yangzhou City from 2015 to 2021, decreasing from 51.75 (interquartile range, 32.82) µg/m3 in 2015 to 28.00 (interquartile range, 23.42) µg/m3 in 2021. The median average annual number of non-accidental mortality, mortality of respiratory diseases and mortality of circulatory diseases were 96 (interquartile range, 22), 9 (interquartile range, 5) and 38 (interquartile range, 13) cases, respectively. The greatest effects of per 10 μg/m3 increase in PM2.5 mass concentration on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases were seen at a cumulative lag of 1 day (ER=0.528%, 95%CI: 0.293%-0.763%), a cumulative lag of 2 days (ER=0.917%, 95%CI: 0.125%-1.714%) and a cumulative lag of 1 day (ER=0.595%, 95%CI: 0.232%-0.961%), respectively. The number of excess mortality caused by PM2.5 on non-accidental mortality, mortality of respiratory diseases, and mortality of circulatory diseases in Yangzhou City from 2015 to 2021 were 2 125, 412 and 977 cases, respectively; compared with 2015, the number of excess mortality in 2021 decreased by 66.95%, 75.53% and 64.42%, respectively. Conclusions An increase in the mass concentration of atmospheric PM2.5 may elevate the risk of excess mortality among residents. Compared to 2015, the number of excess deaths attributed to exposure to atmospheric PM2.5 declined in 2021.