OBJECTIVE To compare the antihypertensive efficacy of sacubitril/valsartan versus benazepril in patients with perimenopausal hypertension， as well as their impacts on ventricular remodeling and inflammatory fibrosis. METHODS A total of 206 perimenopausal hypertensive patients in our hospital from January 1， 2023 to December 30， 2024 were retrospectively included.These patients were enrolled and divided into benazepril group （105 cases） and sacubitril/valsartan group （101 cases）. Benazepril group received Benazepril hydrochloride tablet， and sacubitril/valsartan group received Sacubitril valsartan sodium tablet. All patients were treated for 6 months. The blood pressure（systolic blood pressure and diastolic blood pressure） and blood pressure control status before and after treatment， echocardiographic indicators （left ventricular ejection fraction， left ventricular mass index， relative wall thickness， and early-diastolic peak transmitral flow velocity/early-diastolic peak velocity of the mitral annulus）， inflammatory fibrosis related indicators（high-sensitivity C-reactive protein，ratio of monocytes to lymphocytes，and ratio of neutrophils to lymphocytes）， as well as the occurrence of adverse reactions（hypotension，hyperkalemia，and angioedema） were observed in both groups before and after treatment. RESULTS The blood pressure control rate was significantly higher in the sacubitril/valsartan group than in benazepril group （ P ＜0.05）. After treatment， the blood pressure， echocardiographic indicators（except for left ventricular ejection fraction） ，and inflammatory fibrosis related indicators were significantly lower than those before treatment within the same group， and the sacubitril/valsartan group were significantly lower than the benazepril group （ P ＜0.05）. There were no statistically significant differences in the incidence of hypotension， hyperkalemia， angioedema， and overall adverse drug reactions between the two groups （ P ＞0.05）. CONCLUSIONS Compared with benazepril， sacubitril/valsartan provides superior blood-pressure control， reverses ventricular remodeling， attenuates inflammatory fibrosis in perimenopausal hypertensive patients， while maintaining a similar safety profile.

Rheumatoid arthritis （RA） is a chronic systemic autoimmune disease characterized by symmetrical polyarthritis， which may lead to joint deformity and loss of joint function in the long term， severely impairing patients' quality of life. Danggui Niantongtang， originated from Medical Revelations by Zhang Yuansu in the Jin Dynasty， has the effects of clearing heat and draining dampness， dispelling wind and alleviating pain， and serves as a classic formula for treating RA damp-heat stagnation syndrome. By searching CNKI， Wanfang， PubMed and other databases， the author systematically reviewed the clinical efficacy and experimental research of Danggui Niantongtang in the treatment of RA， and elucidated its mechanisms of action， so as to provide a valuable reference for future clinical and basic research of Danggui Niantongtang in the field of RA. Clinical studies demonstrated that Danggui Niantongtang can improve core symptoms in RA patients with the damp-heat stagnation syndrome， including joint swelling and pain， morning stiffness and limited joint mobility， decrease inflammatory markers such as C-reactive protein （CRP） and erythrocyte sedimentation rate （ESR）， and facilitate postoperative rehabilitation in RA patients undergoing total knee arthroplasty （TKA）. When combined with Western medicines such as methotrexate， it can enhance the anti-inflammatory efficacy and mitigate adverse reactions， including gastrointestinal discomfort and hepatic injury. Experimental studies revealed that this formula can modulate the inflammatory cytokine network， promote synoviocyte apoptosis， inhibit abnormal synoviocyte autophagy， suppress synovial angiogenesis， and maintain intestinal flora homeostasis. However， several limitations exist in current research， such as insufficient clinical quality， unclear interaction between mechanisms and networks， and insufficient research on dosage form optimization. In the future， high-quality clinical research， multi-omics mechanistic studies， and dosage form improvement are needed to provide scientific basis for its clinical promotion and in-depth research.

ObjectiveTo observe the effects of Tongluo Baoshen prescription （TLBS）-containing serum on the rat podocyte injury induced by lipopolysaccharide （LPS） and explore the potential mechanisms. MethodsSD rats were used to prepare the blank serum， losartan potassium-containing serum， and low-， medium-， and high-dose TLBS-containing sera. Rat podocytes were cultured in vitro， and the effects of drug-containing sera on podocyte viability were detected by the cell counting kit-8 （CKK-8） method. The optimal intervention volume fraction of drug-containing sera and the optimal concentration of LPS for inducing the podocyte injury were determined. Rat podocytes were grouped as follows： normal control （NC， 10% blank serum）， model control （MC， 20.00 mg·L^-1 LPS+10% black serum）， losartan potassium （LP， 20.00 mg·L^-1 LPS+10% losartan potassium-containing serum）， low-dose TLBS （TLBS-L， 20.00 mg·L^-1 LPS+10% low-dose TLBS-containing serum）， medium-dose TLBS （TLBS-M， 20.00 mg·L^-1 LPS+10% medium-dose TLBS-containing serum）， and high-dose TLBS （TLBS-H， 20.00 mg·L^-1 LPS+10% high-dose TLBS-containing serum）， and the interventions lasted for 48 h. The ultrastructure of podocytes was observed under a transmission electron microscope. The podocyte apoptosis was detected by the terminal deoxynucleoitidyl transferase mediated nick-end labeling （TUNEL） kit. Immunofluorescence was used to detect the expression of gasdermin D N-terminal fragment （GSDMD-NT） in podocytes. The mRNA and protein levels of G protein-coupled receptor family C group 5 member B （GPRC5B）， nuclear factor-κB （NF-κB） p50， NF-κB p52， NF-κB p65， Rel B， c-Rel， NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， GSDMD-NT， interleukin （IL）-1β， IL-18， nephrin， integrin α₃， and integrin β₁ in podocytes were determined by real-time quaritiative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the NC group， the MC group showed reduced podocyte protrusions and organelles， segmental missing of cell membranes， increased and swollen mitochondria， irregular nuclear membranes， light chromatin， increased TUNEL fluorescence-positive nuclei （P<0.01）， obviously enhanced fluorescence intensity of GSDMD-NT， up-regulated mRNA and protein levels of GPRC5B， NF-κB p50， NF-κB p52， NF-κB p65， Rel B， c-Rel， NLRP3， caspase-1， GSDMD-NT， IL-1β， and IL-18 （P<0.01）， and down-regulated mRNA and protein levels of nephrin， integrin α₃， and integrin β₁ （P<0.01） in podocytes. Compared with the MC group， the LP， TLBS-M， and TLBS-H groups showed improved ultrastructure of podocytes with increased protrusions， intact cell membranes， reduced organelles， and alleviated mitochondrial swelling， decreased TUNEL fluorescence-positive nuclei （P<0.01）， weakened fluorescence intensity of GSDMD-NT， down-regulated mRNA and protein levels of GPRC5B， NF-κB p50， NF-κB p52， NF-κB p65， Rel B， c-Rel， NLRP3， caspase-1， GSDMD-NT， IL-1β， and IL-18 （P<0.01）， and up-regulated mRNA and protein levels of nephrin， integrin α₃， and integrin β₁ （P<0.05， P<0.01）. Moreover， the changes above were the most obvious in the TLBS-H group. ConclusionThe TLBS-containing serum can regulate the GPRC5B/NF-κB/NLRP3 pathway to inhibit pyroptosis， thereby ameliorating the podocyte injury induced by LPS.

[摘 要] 目的：探讨甲硫氨酸限制对肺腺癌（LUAD）细胞增殖、凋亡及磷酸戊糖途径的影响。方法：将H1299、A549细胞分为Met+组和Met−组，分别用含100 μmol/L或不含甲硫氨酸的培养基连续培养4 d，采用细胞计数法评估甲硫氨酸处理对H1299和A549细胞增殖的影响，PI染色法检测细胞周期分布，Annexin Ⅴ-PE/7AAD标记细胞凋亡，利用DCFH-DA探针检测细胞内ROS水平，WST-8法和DTNB法分别测定细胞内NADPH与GSH含量；通过癌症基因组图谱（TCGA）数据库分析葡萄糖-6-磷酸脱氢酶（G6PD）和6-磷酸葡萄糖酸脱氢酶（6PGD）表达与甲硫氨酸代谢通路的关系；采用WB法检测甲硫氨酸处理及回补甲硫氨酸下游代谢产物S-腺苷甲硫氨酸（SAM）对LUAD细胞中磷酸戊糖途径关键酶G6PD和6PGD表达的影响。结果：甲硫氨酸限制显著抑制H1299和A549细胞增殖（均P < 0.01），将细胞周期阻滞于G2/M期（均P < 0.05），显著升高细胞内总ROS水平（均P < 0.001）并促进细胞凋亡（均P < 0.001）；同时，甲硫氨酸限制显著降低了细胞内NADPH和GSH水平（均P < 0.01），抑制DNA合成（均P < 0.01）。分析TCAG数据发现，G6PD和6PGD表达水平与甲硫氨酸代谢通路呈正相关（均P < 0.001），甲硫氨酸限制下调G6PD和6PGD蛋白表达（均P < 0.01），而回补SAM可部分逆转甲硫氨酸限制对G6PD和6PGD的表达的抑制（均P < 0.01），提示甲硫氨酸通过SAM合成调控磷酸戊糖途径。结论：甲硫氨酸限制通过抑制磷酸戊糖途径抑制LUAD细胞增殖，为甲硫氨酸限制疗法治疗LUAD提供实验依据。

OBJECTIVE To discuss the effect mechanism of atractylodin （ATR） on lung injury and airway inflammation in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD）. METHODS AECOPD model was established using smoke exposure and intratracheal injection of lipopolysaccharide. Rats were randomly grouped into model group， ATR low-， medium- and high-dose groups （25， 50 and 100 mg/kg）， as well as high-dose ATR+anisomycin [ANS， c-Jun N-terminal kinase （JNK） activator] group （100 mg/kg ATR+5 mg/kg ANS）. Additionally， a non-modeled control group was set up， with 12 rats in each group. Rats in each group were intraperitoneally injected with the corresponding drug solution/normal saline once daily for 14 consecutive days. After the last medication， lung function [peak expiratory flow （PEF）， the ratio of forced expiratory volume （FEV） to forced vital capacity （FVC）， arterial partial pressure of oxygen （PaO2）]， as well as the number of inflammatory cells and the levels of inflammatory cytokines [interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and IL-1β] in bronchoalveolar lavage fluid （BALF）， were measured. The pathological morphology of lung tissue in rats was observed. 163.com The apoptosis of lung epithelial cells was detected， and the expression levels of proteins related to the JNK/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway in rat lung tissues were detected. RESULTS Compared with control group， PEF， FEV/FVC and PaO2 of model group were slowed or decreased significantly （P＜0.05）. The number of white blood cells， neutrophils， lymphocytes and macrophages， as well as the levels of IL-1β， TNF-α and IL-6 in BALF， along with the pathological score， the apoptosis rate of lung epithelial cells， and the phosphorylation levels of JNK and p38 MAPK proteins in lung tissues， were all increased or raised significantly （P＜0.05）； lung tissue exhibited severe damage， with disordered cell arrangement and marked infiltration of inflammatory cells. Compared with model group， the levels of above quantitative indicators in rats from all ATR dosage groups showed significant improvement in a dose-dependent manner （P＜0.05）； moreover， the pathological damage in lung tissue was alleviated， with cells arranged in a regular and orderly fashion. Compared with ATR high-dose group， the levels of the above quantitative indicators in rats from the high-dose ATR+ANS group were significantly reversed （P＜0.05）， and the pathological damage in lung tissue was exacerbated. CONCLUSIONS ATR inhibits airway inflammation by suppressing the activity of the JNK/p38 MAPK signaling pathway， thereby improving lung tissue damage in AECOPD rats.

Objective: To investigate the trend in reported incidence of hepatitis B and to assess the effects of age, period, and birth cohort among people aged <30 years in Quzhou City, Zhejiang Province from 2005 to 2024. Methods: Reported cases of hepatitis B among people aged <30 years in Quzhou City from 2005 to 2024 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The reported incidence was calculated. The average annual percent change (AAPC) was used to analyze the trend in reported incidence from 2005 to 2024. An age-period-cohort model was employed to analyze the effects of age, period, and birth cohort on the reported incidence of hepatitis B. Results: From 2005 to 2024, a total of 3 805 hepatitis B cases were reported among people aged <30 years in Quzhou City, with an average annual reported incidence of 31.61/100 000. The average annual reported incidence of hepatitis B was higher in males than in females (36.65/100 000 vs. 26.08/100 000, P<0.05). From 2005 to 2024, the reported incidence of hepatitis B among the entire people aged <30 years, as well as among males and females separately in Quzhou City, showed declining trends (AAPC=-9.887%, -10.415%, and -9.320%, respectively, all P<0.05). The age-period-cohort model analysis revealed that the incidence first decreased and then increased with age, declining from 4.21/105 in the age group of 0-<5 years to 2.07/105 in the age group of 10-<15 years, before rising to 22.49/105 in the age group of 25-<30 years. Using the 2010-2014 period as the reference, the risk of hepatitis B showed a decreasing trend over time. The RR value decreased from 1.842 (95%CI: 1.433-2.366) for 2005-2009 to 0.446 (95%CI: 0.294-0.675) for 2020-2024. Using the 2000-2004 birth cohort as the reference, the risk showed a decreasing trend with more recent birth years. The highest risk was observed in the 1980-1984 birth cohort, with an RR value of 4.731 (95%CI: 3.083-7.259). The age, period, and cohort effects on the reported incidence of hepatitis B among males and females were generally consistent with those observed in the entire population. Conclusions From 2005 to 2024, the reported incidence of hepatitis B among people aged <30 years in Quzhou City showed a declining trend, while exhibiting a pattern of first decreasing and then increasing with age. Furthermore, the risk of hepatitis B incidence demonstrated a decreasing trend over both time periods and birth cohorts.

Objective To investigate the relationship between the expression of serum long non coding RNA nuclear-enriched abundant transcript 1(lncRNA NEAT1)and microRNA-106a-5p(miR-106a-5p)and the severity and prognosis of sepsis patients.Methods A total of 185 patients with sepsis who were diagnosed and treated in this hospital from August 2021 to July 2024 were selected as the study group,and another 215 healthy volunteers who underwent physical examinations in this hospital during the same period were selected as the control group.The research group was divided into the mild group(n=92),the severe group(n=58)and the shock group(n=35)according to the severity of the disease.The research group was divided into the good prognosis group(n=121)and the poor prognosis group(n=64)according to the prognosis.The expres-sions of lncRNA NEAT1 and miR-106a-5p were detected by real-time fluorescence quantitative polymerase chain reaction,and the correlation of the expressions of lncRNA NEAT1 and miR-106a-5p in the study group was analyzed by Pearson correlation analysis.The binding sites of lncRNA NEAT1 and miR-106a-5p were an-alyzed by StarBase,and the influencing factors of poor prognosis in patients were analyzed by multivariate Lo-gistic regression.The receiver operating characteristic curve was used to analyze the diagnostic value of the combination of lncRNA NEAT1 and miR-106a-5p for poor prognosis in patients.Results The expression of lncRNA NEAT1 in the study group was higher than that in the control group,and the expression of miR-106a-5p was lower than that in the control group,the difference was statistically significant(P＜0.05).The expressions of lncRNA NEAT1 and miR-106a-5p in the study group were negatively correlated(r=-0.413,P＜0.001),and there were binding sites between the two.With the increase of the severity of sepsis,the ex-pression of lncRNA NEAT1 increased and the expression of miR-106a-5p decreased,and the difference was statistically significant(P＜0.05).The acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,sequential organ failure assessment(SOFA)score,tumor necrosis factor-α,C-reactive protein,and ln-cRNA NEAT1 in the poor prognosis group were higher than those in the good prognosis group,while the ex-pression of miR-106a-5p was lower than that in the good prognosis group,the difference was statistically sig-nificant(P＜0.05).Elevated APACHE Ⅱ score,SOFA score and lncRNA NEAT1 were independent risk fac-tors for poor prognosis in patients,and miR-106a-5p was an independent protective factor(P＜0.05).The ar-ea under the curve of the combined diagnosis of the two was 0.918(95％CI:0.868-0.953),which was supe-rior to the separate diagnosis of each(Zcombined with lncRNA NEAT1=4.112,Zcombined with miR-106a-5p=4.023,P＜0.05).Con-clusion With the increase of disease severity in patients with sepsis,the expression of lncRNA NEAT1 in-creases and the expression of miR-106a-5p decreases.The combined diagnosis of the two for poor prognosis in patients has a high clinical value.

Objective To investigate the effect of total paeony glycoside(TPG)on cerebral ischemia-reperfusion injury(CI/RI)of rats.Methods The rats were randomly divided into sham surgery(sham)group,CI/RI model group(simple CI/RI group),positive control group(nimodipine group,5 mg/kg),low-dose TPG group(TPG-L group,27 mg/kg),a high-dose TPG group(TPG-H group,54 mg/kg)and a high-dose TPG+NOD-like receptor thermal protein domain associated protein 3(NLRP3)activator diethyl dithiocarbamate(DDC)group(TPG-H+DDC group,54 mg/kg TPG and 30 mg/kg DDC),with 18 rats in each,administered once a day for 7 consecutive days.After the administration,the neurological deficit score of the rats was evaluated.Nissl staining microscopy was applied to observe neuronal activity in brain tissue.2,3,5-triphenyltetrazolium chloride(TTC)staining microscopy was applied to detect the area of cerebral infarction in rats.The level of interleukin-1β and IL-18 in brain tissue was measured by ELISA method.Western blot was applied to detect the expression of purinergic receptor P2X ligand-gated ion channel 7(P2X7R)/NLRP3 signaling pathway related proteins and pyroptosis related proteins such as apoptosis associated speck like protein containing a CARD(ASC)and cysteine protease 1(caspase-1)proteins in brain tissue.Results Compared with the sham group,the neurological deficit score,infarct area,level of IL-1β and IL-18 in brain tissue and protein expression of P2X7R,NLRP3,ASC,and caspase-1 in brain tissue of rats in the simple CI/RI group were significantly increased(P<0.05),while the proportion of Nissl body positive cells in brain tissue was significantly reduced(P<0.05).The change in corresponding indicators of rats in the nimodipine group,TPG-L group,and TPG-H group was opposite to those in the simple CI/RI group(P<0.05).NLRP3 acti-vator DDC antagonized the inhibitory effect of TPG on cell pyroptosis in CI/RI rats.Conclusions TPG may inhibit brain injury in CI/RI rats by down-regulating the P2X7R/NLRP3 pathway.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.