OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

OBJECTIVE: To investigate the effects of Bushen Huoxue Granule on the ubiquitin-proteasome system (UPS) in an in vitro model of Parkinson's disease. METHODS: After treated with 1-methyl-4-phenylpyridinium (MPP⁺, 1 mmol/L) for 24 h, the cells were incubated with drug-free serum, Madopar-containing serum or Bushen Huoxue Granule-containing serum (BCS, 5%, 10%, and 20%) for another 24 h. The levels of α-synuclein (α-syn), tyrosine hydroxylase (TH) and UPS-related proteins were detected by Western blot. The expression levels of α-syn in PC12 cells were also analyzed by Western blot after treated with proteasome inhibitor MG132 and WT-α-syn plasmid transfection, respectively, as well as the alterations induced by subsequent BCS intervention. Immunocytochemistry was performed to determine the changes in α-syn phosphorylation at serine 129 (pSer129-α-syn) expression. The 20S proteasome levels were measured by enzyme-linked immunosorbnent assay. RESULTS: BCS (volume fraction ⩽20%) intervention could alleviate the MMP⁺-induced cell viability decrease (P<0.05). In the MPP⁺ treated cells, α-syn was up-regulated, while TH and proteins of UPS such as ubiquitin (Ub), Ub binding with Ub-activating enzyme (UBE1), Parkin and Ub C-terminal hydrolase-1 (UCHL-1) were down-regulated (P<0.05). BCS intervention could attenuate the above changes (P<0.05). The activity of BCS on blocking α-syn accumulation was weakened by MG132 (P<0.05). While α-syn level was significantly increased in cells transfected with plasmid, and reduced by BCS intervention (P<0.05). pSer129-α-syn was increased in MPP⁺-induced PC12 cells, whereas decreased by later BCS intervention (P<0.05). The 20S proteasome activity of MPP⁺-induced PC12 cells was decreased, but increased after BCS intervention (P<0.05). CONCLUSION BCS intervention protected UPS function, increased 20S proteasome activity, promoted pathological α-syn clearance, restored cell viability, and reversed the damage caused by MPP⁺ in the in vitro model of Parkinson's disease.
PC12 Cells ; alpha-Synuclein/metabolism* ; Rats ; Animals ; 1-Methyl-4-phenylpyridinium/toxicity* ; Proteasome Endopeptidase Complex/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Ubiquitin/metabolism* ; Cell Survival/drug effects* ; Phosphorylation/drug effects* ; Tyrosine 3-Monooxygenase/metabolism*

ObjectiveTo investigate the association between neutrophil-to-lymphocyte and platelet ratio （NLPR） and recompensation in patients with hepatitis B cirrhotic ascites， and to establish an individualized risk prediction model. MethodsThe patients with hepatitis B cirrhotic ascites who were hospitalized in Department of Gastroenterology， The General Hospital of Western Theater Command of Chinese PLA， from January 2015 to December 2022 were enrolled. General information and laboratory markers were collected， and NLPR was calculated. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the chi-square test with correction was used for comparison of categorical data between two groups. The subjects were randomly divided into a training set and a validation set at a ratio of 7∶3. In the training set， univariate and multivariate binary Logistic regression analyses were used to investigate the independent influencing factors for recompensation in patients with hepatitis B cirrhotic ascites， and a nomogram was established； the receiver operating characteristic （ROC） curve was used to assess the value of the new model in predicting recompensation in patients with hepatitis B cirrhotic ascites， and the Delong test was used for comparison of the area under the ROC curve （AUC）. The calibration curve and the decision curve were plotted for the model， and the model was assessed in terms of degree of fitting and predictive benefits. ResultsA total of 360 patients were enrolled， among whom134 achieved recompensation. There were 252 patients in the training set and 108 patients in the validation set， and there were no significant differences in baseline characteristics between the two groups （all P>0.05）. The Logistic regression analysis showed that the onset of hepatic encephalopathy （odds ratio ［OR］=0.066， 95% confidence interval ［CI］： 0.008 — 0.545， P=0.012）， NLPR （OR=0.950， 95%CI： 0.912 — 0.989， P=0.012）， alpha-fetoprotein （OR=1.012， 95%CI： 1.005 — 1.020， P<0.001）， and albumin （OR=1.096， 95%CI： 1.031 — 1.166， P=0.003） were independent influencing factors for recompensation in patients with hepatitis B cirrhotic ascites. The above four factors were included in a nomogram predictive model， which had an AUC of 0.776， a sensitivity of 66.5%， and a specificity of 76.3% in the training set and an AUC of 0.746， a sensitivity of 63.4%， and a specificity of 75.7% in the validation set， while Model for End-Stage Liver Disease score， Child-Pugh score， and albumin-bilirubin score had an AUC of 0.574， 0.628， and 0.621， respectively. The nomogram model had a better performance than the other three scores in predicting recompensation in patients with hepatitis B cirrhotic ascites （Z=4.191， 3.369， and 3.527， P<0.001， P=0.001， and P<0.001）. The calibration curve and the decision curve showed that the model had a good degree of fitting， and the decision made using this model could bring net benefits. ConclusionNLPR has a good value in predicting recompensation in patients with hepatitis B cirrhotic ascites， and the nomogram model established can help to predict recompensation in such patients in clinical practice.

ObjectiveTo investigate the effect of the multidisciplinary team （MDT） management model in improving the prognosis of patients with cirrhotic portal hypertension. MethodsA total of 86 patients with cirrhotic portal hypertension who were admitted to Shenzhen Third People’s Hospital from May 2022 to July 2024 were enrolled， and according to whether the MDT treatment regimen was implemented， they were divided into execution group with 51 patients and non-execution group with 35 patients. Baseline clinical data were collected， and the patients were observed in terms of gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death from admission to the end of follow-up （January 2025）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves for the cumulative incidence rates of endpoint events （gastrointestinal bleeding， hepatic encephalopathy， liver cancer， and death）， and the Log-rank test was used for comparison between groups. The Cox proportional-hazards regression model analysis was used to investigate the effect of MDT management on the prognosis of patients. ResultsThere were significant differences between the execution group and the non-execution group in diameter of the portal vein （t=1.216， P=0.017） and ascites （χ²=4.515， P=0.034） at baseline. The patients were followed up for 14.6±6.2 months， and the survival curve analysis showed that there was a significant difference in the cumulative incidence rate of gastrointestinal bleeding between the two groups （χ²=4.573， P=0.024）， while there were no significant differences in the incidence rates of other outcome events between the two groups （all P>0.05）. The Cox regression analysis showed that the execution group had a reduced risk of gastrointestinal bleeding （hazard ratio=0.262， 95% confidence interval： 0.110 — 0.630， P=0.003）. ConclusionImplementation of the MDT treatment regimen can significantly reduce the short-term risk of gastrointestinal bleeding in patients with cirrhotic portal hypertension， while its long-term benefits require further follow-up verification.

Background::China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019.Methods::The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported.Results::The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends.Conclusions::The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Background The subway environment, characterized by dense crowds, relatively enclosed architectural structures, and insufficient ventilation, poses various health hazards. Population health risk attributable to subway hygiene have become an important public health issue. Objective To evaluate the current environmental hygiene of metro line X in Nanjing, and to provide a scientific basis for the prevention and control of harmful factors and the establishment of relevant standards. Methods Station halls, platforms, and carriages of Nanjing metro line X were monitored in March 2023. Six stations were selected by stratified sampling, and monitored once during the morning peak hours (9:00—11:00). Carriage monitoring was conducted after a full day of operation (21:00—22:00). The monitoring indicators included physical factors such as temperature, relative humidity, wind speed, illuminance, and noise (A-weighted); air quality factors such as carbon dioxide (CO₂), carbon monoxide (CO), respirable particulate matter (PM₁₀), fine particulate matter (PM_2.5), ammonia (NH₃), formaldehyde, benzene, toluene, xylene, total volatile organic compounds (TVOC), ozone (O₃), total bacterial count, and total fungi count; hygiene status of the inner surface of the central air conditioning ventilation system, such as dust accumulation, total bacterial count, and total fungi count; supply air, such as PM_10, PM_2.5, total bacterial count, and total fungi count; and surface microorganisms on objects, such as total bacterial count, total fungi count, coliform bacteria, and Staphylococcus aureus. Results were evaluated and discussed according to Hygienic indicators and limits for public places (GB 37488-2019) and Hygienic specification of central air conditioning ventilation systems in public buildings (WS 394-2012). Results The environmental temperature medians (P₂₅, P₂₅) in the platforms and carriages of Nanjing metro line X were 20.7 (19.95, 21.65) ℃ and 21.8 (19.80, 35.80) °C, respectively, which exceeded the standard limits. The relative humidity and noise level in the carriages were 38.80% (24.6%, 46.3%) and 79.50 (76.25, 82.00) dB, respectively, failing to meet the national health standards. The total fungi count in supply air in 22.2% of the monitoring points exceeded the standard value. Coliform bacteria and Staphylococcus aureus were detected on the surfaces of some high-touch objects, with the bathroom faucet being the most severely contaminated. The medians (P₂₅, P₂₅) of temperature [21.8 (19.8, 35.8) ℃], wind speed [0.48 (0.39, 1.02) m·s⁻¹], noise [79.5 (76.25, 82.00) dB, and CO₂ content [0.079% (0.070%, 0.091%)] in the carriages were higher than those in the station halls and platforms (P<0.05). There were significant differences in microclimate, air particulate matter, and air microbial levels between urban and suburban stations (P<0.05); the concentrations of PM₁₀ [0.076 (0.046, 0.079) mg·m⁻³)] and PM_2.5 [0.063 (0.044, 0.068) mg·m⁻³)] in suburban stations were 2 times higher than those of urban stations. The temperature [21.60 (20.45, 21.80) ℃], humidity [45.20% (40.95%, 50.10%)], CO₂ [0.100% (0.100%, 0.825%)], and PM₁₀ concentration [0.070 (0.041, 0.080) mg·m⁻³] in transfer stations were all significantly higher than those in non-transfer stations (P<0.05). The temperature at stations was significantly correlated with the CO₂ content (r_s=0.6107, P<0.001), the concentration of air particulate matter and the content of air microorganisms were positively correlated with the relative humidity (P<0.05), and the air PM₁₀ and PM_2.5 concentrations were positively correlated with the total bacterial count and the total fungi count (P<0.05). There was a significant positive correlation between the total bacterial count and the total fungi count on the inner surface of the air duct (r_s=0.5877, P<0.05). The concentrations of PM₁₀ and PM_2.5 in supply air were positively correlated (r_s=0.9635, P<0.001), and both were also positively correlated with the total bacterial count in supply air (r_s=0.6848 and 0.6511, P=0.002 and 0.003). Conclusion All chemical factors of metro line X in Nanjing meet the national standards, while physical factors (temperature, relative humidity, wind speed, and noise) exceed the standards, and coliform bacteria and Staphylococcus aureus are detected on the surfaces of bathroom faucets and carriage poles. It is advisable to reinforce microclimate management and noise reduction measures in carriages, while ensuring regular cleaning and disinfection of public facilities and equipment.

Objective To investigate the clinical efficacy of Xuanfei Tongluo Pingchuan Decoction in treating patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and to explore its regulatory mechanism on immune function and inflammatory response.Methods A retrospective study was conducted in 122 patients with AECOPD of phlegm-stasis obstructing lung type,and the patients were divided into an observation group and a control group according to the therapy,with 61 patients in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xuanfei Tongluo Pingchuan Decoction on the basis of treatment for the control group.The treatment lasted for 14 days.Before and after treatment,the patients of the two groups were observed in the changes of pulmonary function indicators,6-minute walking distance(6MWD),COPD Assessment Test(CAT)scores,immune function indicators,and serum inflammatory factors.After treatment,the clinical efficacy and the overall occurrence rate of the adverse reactions were compared between the two groups.Results(1)After 14 days of treatment,the total effective rate of the observation group was 95.08%(58/61),and that of the control group was 77.05%(47/61).The intergroup comparison showed that the therapeutic effect of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,pulmonary function indexes such as the forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and peak expiratory flow(PEF)of the two groups were significantly improved compared with those before treatment(P＜0.05),and the effect on improving all pulmonary function indexes in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the 6MWD of the two groups were significantly higher(P＜0.05)and the CAT scores were significantly lower than those before treatment(P＜0.05),and the observation group was significantly superior to the control group in terms of improving the 6MWD and decreasing CAT scores(P＜0.01).(4)After treatment,the levels of immune function indicators of T lymphocyte subsets CD4+ and CD4+/CD8+ in the two groups were significantly higher than those before treatment(P＜0.05),and CD8+ level was significantly lower than that before treatment(P＜0.05),and the observation group had stronger effect on increasing T lymphocyte subsets CD4+ and CD4+/CD8+ levels and on decreasing CD8+ level than the control group(P＜0.01).(5)After treatment,the serum levels of inflammatory factors C-reactive protein(CRP)and tumor necrosis factor alpha(TNF-α)in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the effect on lowering the levels of serum CRP and TNF-α in the observation group was significantly superior to that in the control group(P＜0.01).(6)During the trial,the total incidence of adverse reactions in the observation group was 3.28%(2/61)and that in the control group was 6.56%(4/61),and the intergroup comparison showed that the difference was not statistically significant between the two groups(P＞0.05).Conclusion Xuanfei Tongluo Pingchuan Decoction can effectively alleviate the symptoms of cough and expectoration in AECOPD patients,improve the lung function and immune function,and reduce the inflammatory response.During the treatment,no obvious adverse reactions occur and the therapy is safe and effective.

Objective To analyze the burden and changing trend of testicular cancer in China from 1990 to 2019.Methods Based on the 2019 Global Burden of Disease Database(GBD 2019),analyze the incidence,mortality,disability-adjusted life years(DALYs),years of life lost(YLLs),years lived with disability(YLDs)and their variation trend of testicular cancer in Chinese population from 1990 to 2019.Evaluating changes in age standardized rate(ASR)by calculating annual estimated percentage change(EAPC).According to the age grouping,analyze the age distribution characteristics of testicular cancer disease burden by age group.Results In 2019,the incident cases,deaths,age-standardized incidence rate,and age-standardized mortality rate of testicular cancer in China were 17.17×103,1.21×103,2.39/105,and 0.16/105,respectively.Compared to 1990,incident cases,deaths,and age-standardized incidence rate increased obviously in China,which was consistent with the global change trend,while the increase was higher than the global level.However,both Chinese and global age-standardized mortality rate showed a downward trend.From 1990 to 2019,DALYs,YLLs and YLDs of testicular cancer increased by 29.66%,9.83%and 720.91%respectively in China.The two age groups,0-15 years group and 30-35 years group,were with highest incidence of testicular cancer,while the highest disease burden of testicular cancer was 30-35 years.Conclusion From 1990 to 2019,the disease burden of testicular cancer in China showed an upward trend.Adolescents and young adults should be the priority population for screening and prevention due to their higher incidence and disease burden.

Objective To observe the effects of total saponins of Trillium tschonoskii Maxim(TST)on vascular cognitive impairment(VCI),neurovascular units(NVUs),and neural circuit integrity in rats.Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham-operated group,model group,TST group(intragastric administration,100 mg/kg),and donepezil group(intragastric administration,0.45 mg/kg),and then subjected to ischemic stroke by 2-VO method(bilateral common carotid artery ligation)or sham surgery.After 28 days of intragastric administration,Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group.HE and Nissl staining were used to observe the pathological changes of brain tissue in rats.The expression of synuclein(SYN)in rat hippocampus was observed by immunohistochemical staining.Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining.Western blotting was used to detect the expression levels of IL-1β,IL-10,vascular endothelial growth factor A(VEGFA),postsynaptic density protein 95(PSD95),and growth associated protein 43(GAP43)in rat's hippocampus in each group.Results In Mirros water maze test,rats in model group showed significant prolonged escape latency(P＜0.05),and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant(P＜0.05)than those in sham-operated group;while rats in TST group and donepezil group showed significant shortened escape latency(P＜0.01),and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant(P＜0.05)than those in model group.Compared of sham-operated group,model group showed a decrease in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P＜0.05).Compared with model group,TST group and donepezil group showed an increase in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P＜0.05).Western blotting showed a significant increase in the expression of IL-1β and VEGF(P＜0.05),and a decrease in the expression of IL-10,PSD95,and GAP43(P＜0.01)in rat's hippocampus of model group than those in sham-operated group.Compared with model group,TST group and donepezil group showed a significant decrease in the expression of IL-1β(P＜0.05),and an increase in the expression of VEGFA,IL-10,and GAP43(P＜0.05).Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats,suggesting its significance as a potential drug for apoplexy.