ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Objective: To understand the prevalence and related factors of tobacco use among junior high school students in Beijing, so as to provide evidence to effectively conduct tobacco control intervention strategy. Methods: From April to June in 2019 and 2023, 6 489 and 6 898 junior high school students were selected by the probability proportion to size(PPS) method, and a total of 13 387 questionnaires were completed. Questionnaire on tobacco monitoring among junior high school students in Beijing was completed by selffilling. The monitoring content included demographic information, secondhand smoke exposure, tobacco product use, tobacco awareness, etc. Chisquare test was used to compare the difference of various indicators in different groups, and multivariate Logistic regression analysis was adopted to analysis the influencing factors related to the current smoking among junior high school students. Results: In 2019,the current traditional cigarettes and ecigarette smoking rates among junior high school students in Beijing were 1.34%, 1.88%, respectively, and decreased to 0.81%, 1.06% in 2023 (χ2=8.36, 15.17, P＜0.01). The attempted traditional cigarettes and ecigarette smoking rates among junior high school students in Beijing decreased from 6.67%, 6.47% in 2019 to 3.93%, 4.16% in 2023 (χ2=49.99, 35.26, P＜0.01). In 2019, the secondhand smoke exposure rates of junior high school students at homes, indoor public places, and outdoor public places were 31.04%, 44.94%, and 49.88% respectively which decreased to 22.59%, 30.23%, and 36.14% in 2023 (χ2=121.63, 308.60, 257.41, P<0.01). In 2023, male students (OR=2.88), senior students (grade 2 and 3) (OR=4.37, 4.92), disposable pocket money>20 yuan/week (OR=2.01), secondhand smoke exposure at home (OR=2.74), indoor public places (OR=2.64), perception that smoking makes young people more attractive (OR=6.29), and perception that ecigarettes help quit smoking (OR=4.31) were associated with higher tobacco use (P<0.05). Conclusions Tobacco use and secondhand smoke among junior high school students in Beijing decrease significantly. Tobacco control interventions should be provided for junior high school students continuously with a focus on ecigarettes use to promote physical and mental health development among students.

Objective: To explore the association between parental myopia and extracurricular activities before school age with myopia among lower grade students, so as to provide evidence for myopia prevention on low grade students. Methods: From November 2020 to June 2022, a total of 8 368 students of grade 1-3 were selected from Beijing, Liaoning, Zhejiang, Henan, Chongqing, Shaanxi Province by the stratified cluster random sampling and probability sampling methods, and were administered with a questionnaire survey and eye examinations. Multivariate Logistic regression was used to analyze the association between parental myopia and extracurricular activities before school age with myopia among lower grade students. Results: The prevalence of myopia in grade 1-3 was 23.7% in 6 provinces in China. Students who in central area, grade 3, boarding at school, doing homework/reading/writing time ≥1 h/d after school, extracurricular activities ≥1 h in the past week, extracurricular activities before school age, parental myopia, poor reading and writing posture, sleeping time <10 h/d, less exercise time because of homework or extracurricular activities, having annual vision examination had a higher myopia detection rate, with statistically significant differences ( χ 2=36.41, 487.72, 15.97, 21.35, 43.95, 15.33, 54.04, 6.67, 3.88, 20.02, 20.06, P <0.05). After adjusted for the confounding factors, there was a significant interaction between parental myopia and extracurricular activities before school age with myopia ( P interaction <0.01). After adjusting for confounding factors, Logistic regression analysis showed that those having extracurricular activities before school age had a higher risk of myopia ( OR=1.33, 95%CI =1.19-1.56), compared with those who did not. Compared with children without nearsighted parents, children with nearsighted parents had higher prevalence of myopia ( OR=1.64, 95%CI = 1.45- 1.84) ( P <0.05); and the values of indicators ( RERI, API, Index S ) for interaction between parental myopia and extracurricular activities before school age were 0.35, 0.27, 1.37, respectively. Conclusion Both parental myopia and extracurricular activities before school age are associated with myopia among lower grade students, with interactive effects.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective to compare the application value of MELD score,AIMS65 score and platelet-albumin-bilirubin index(PALBI)in the prediction of 28 d death in patients with cirrhosis combined with acute upper gastrointestinal hemorrhage(AUGIB)with a view to providing a reference basis for clinical screening of the most appropriate prognostic prediction score.Methods 378 patients with cirrhosis AUGIB treated in the Department of Critical Care Medicine of the First Affiliated Hospital of Harbin Medical University from January 2020 to December 2023 were retrospectively included,and were categorized into 60(15.9％)in the death group and 318(84.1％)in the survival group based on 28 d survival.Clinical data of all cirrhotic AUGIB patients were retrospectively collected through an online medical record system,and MELD score,AIMS65 score and PALBI score were calculated.The effects of MELD score,AIMS65 score,and PALBI score on death in cirrhotic AUGIB patients were analyzed using binary logistic regression,and finally,the efficacy of these three scores in predicting death in cirrhotic AUGIB patients was assessed using ROC curves.Results Univariate analysis showed that the proportion of diabetes mellitus and hepatic encephalopathy,as well as the prothrombin time,erythrocyte distribution width,C-reactive protein,MELD score,AIMS65 score,and PALBI score were increased and albumin was decreased in the death group compared with the survival group,and the difference was statistically significant(P＜0.05).The results of multifactorial logistic regression analysis showed that after correcting for confounders such as diabetes mellitus,proportion of hepatic encephalopathy,and prothrombin time,the MELD score(OR=1.621,95％CI:1.185-2.217),AIMS65 score(OR=1.914,95％CI:1.361-2.690),PALBI score(OR=1.984,95％CI:1.410-2.791)were independent risk factors for death in patients with cirrhosis AUGIB.The ROC curves showed that the AUCs of MELD score,AIMS65 score,and PALBI score for predicting death at 28 d of cirrhosis were 0.685(95％CI:0.614-0.756),0.828(95％CI:0.771-0.885),0.860(95％CI:0.808-0.913).Conclusion MELD score,AIMS65 score,and PALBI score were all independent risk factors for death in cirrhotic AUGIB patients and suggestive of prognostic risk,with AIMS65 score and PALBI score having the highest predictive value.

Wastewater-based epidemiology(WBE)can effectively assess population health status,but it is lack of analytical methods which can simultaneously analyze a number of pharmaceuticals and biomarkers in wastewater.In this work,a method including sample pretreatment and instrumental detection for quantifying 83 kinds of pharmaceuticals and biomarkers in the influent of wastewater treatment plants(WWTPs)was established by sing solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS).The water sample(200 mL)with 83 kinds of target compounds was divided into two aliquots,which were then enriched and purified using HLB columns at pH=6.7 and pH=2 respectively,followed by elution with 6 mL of methanol and 6 mL of methanol containing 2%(V/V)formic acid,respectively,and then dried by nitrogen blown,concentrated,and finally redissolved to 0.5 mL,filtered through a nylon filter(0.22 μm).The target compounds in the samples were determined using UPLC-MS/MS in electrospray ionization under both positive and negative ion multiple reaction monitoring modes,with quantification using the internal standard method.The method exhibited good linearity(r>0.996)for the 83 kinds of target compounds in the concentration range of 0.1-500 ng/mL,and intra-day and inter-day precisions were 1.2%-16.5%.The recoveries of target substances in pure water and influent samples from a WWTP were 51.6%-166.6%and 56.4%-150.1%,respectively,with relative standard deviations of 0.2%-31.9%and 0.3%-20.9%,respectively.The method detection limits of target compounds were 0.02-7.72 ng/L.This method was applied to determine pharmaceuticals and biomarkers in the influent samples of a WWTP in Guangzhou,and 54 kinds of pharmaceuticals and 4 kinds of biomarkers were detected.The concentrations of acetaminophen and erythromycin were the highest among the pharmaceuticals,1.6-3.4 μg/L and 0.6-1.1 μg/L,respectively.The concentration of caffeine was the highest among the biomarkers,i.e.,33.3-43.9 μg/L.This method had high sensitivity,good stability and accuracy,and was suitable for detection of pharmaceuticals and biomarkers in the influent of WWTP,which could provide analytical method support for conducting studies on WBE.

Major depressive disorder(MDD)is a prevalent con-dition associated with substantial impairment and low remission rates.Traditional antidepressants demonstrate delayed effects,low cure rate,and inadequate therapeutic effectiveness for man-aging treatment-resistant depression(TRD).Several studies have shown that ketamine,a non-selective N-methyl-D-aspartate receptor(NMDAR)antagonist,can produce rapid and sustained antidepressant effects.Ketamine has demonstrated efficacy for reducing suicidality in TRD patients.However,the pharmaco-logical mechanism for ketamine's antidepressant effects remains incompletely understood.Previous research suggests that the an-tidepressant effects of ketamine may involve the monoaminergic,glutamatergic and dopaminergic systems.This paper provides an overview of the pharmacological mechanism for ketamine's anti-depressant effects and discuss the potential directions for future research.

Glutamate,norepinephrine,and their receptors com-prise the glutamatergic and norepinephrine systems,which mu-tually affect each other and play essential roles in mediating vari-ous neuropsychiatric diseases.This paper reviews the functions of N-methyl-D-aspartate receptor(NMDA-R)and α2-adrenergic receptor(α2-AR)and their functional crosstalk at the molecular level in brain in common neuropsychiatric diseases,which would benefit our understanding of neuropathophysiology of psychiatric diseases,drug development and optimization of clinical neuro-psychopharmacology.