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 report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive 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:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

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 explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

Aversive memories are the core pathology of many psychiatric disorders (such as posttraumatic stress disorder and depression), often impeding clinical treatment, which requires validated interventions. Animal researches and preclinical human studies have shown that memories are vulnerable after retrieval due to a memory process known as the memory reconsolidation mechanism, and that interventions during this process can potentially rewrite or update memories. The discovery of the reconsolidation mechanism has sparked a wave of research interest in its potential to rewrite aversive memories. This article presents a brief research history and advances in reconsolidation-based interventions, including pharmacological, non-invasive brain stimulation and behavioral interventions, as well as the biological mechanisms of reconsolidation. It is noted that pharmacological, behavioral and non-invasive brain stimulation interventions are all potential approaches for reconsolidation intervention, with propranolol, extinction/exposure therapy and transcranial magnetic stimulation being relatively effective. It is important to consider the differences between laboratory and clinical studies in future clinical translational research, and to overcome the " boundary conditions" of reconsolidation-based intervention in clinical applications, such as duration of memory retrieval, age of memory, individual differences, and so on, which may affect its efficacy.

Objective:To explore the efficacy of adjusting the dose of imatinib dose in the context of therapeutic drug monitoring (TDM) in patients with gastrointestinal stromal tumors (GISTs) who are receiving adjuvant therapy after complete resection of their tumors.Methods:This was a descriptive study. Inclusion criteria were (1) complete surgical resection with a pathological diagnosis of GIST, (2) postoperative adjuvant therapy with imatinib and dosage adjustment, (3) multiple TDM of imatinib, and (4) complete clinical, pathological, and follow-up data. The data of 70 patients with GISTs treated at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 2015 and December 2023 were collected retrospectively. The study cohort comprised 15 (21.4%) men and 55 (78.6%) women of median age 60 years (range: 25–82). Of the eligible patients, 49 (70.0%) were at high-risk, 14 (20.0%) at intermediate-risk, six (8.6%) at low-risk, and one (1.4%) at very low risk. Patients were followed up by the gastrointestinal stromal tumor clinic every 2–3 months and their plasma concentrations of imatinib were checked. The dose was adjusted to 300 mg/d or 200 mg/d depending on whether they had had ≥ grade III adverse reactions, and whether the first plasma concentration of imatinib was ≥ 1,500 μg/L or between the expected range of 760 μg/L–1,100 μg/L. Studied indicators included adverse reactions, quality of life before and after dose adjustment, and overall survival and recurrence-free survival (RFS) after dose adjustment.Results:Before dose adjustment, all 70 patients received 400 mg of imatinib daily, with initial TDM values of 1,900 ± 568 μg/L, for a median duration of 8.3 months. After dose adjustment, 60 patients received 300 mg daily, with a TDM of 1,216 ± 350 μg/L, whereas 10 received 200 mg daily, with a TDM of 1,023 ± 269 μg/L. The median duration of treatment after dose adjustment was 23.4 months. Compared with those whose dosages were not adjusted, the incidence of bone marrow suppression was significantly lower (74.3% [52/70] vs. 51.4% [36/70], χ 2=9.202, P=0.010); as were the incidences of edema (95.7% [67/70] vs. 50.0% [35/70], χ 2=40.526, P<0.001); skin reactions (70.0% [49/70] vs. 32.9% [23/70), χ 2=22.495, P<0.001); and gastrointestinal reactions (38.6% [27/70] vs. 10.0% [7/70], χ 2=15.899, P<0.001) in those whose dosages were adjusted. The average total scores for physical health before and after dose adjustment were 76 ± 5 and 88 ± 4, respectively; whereas the mental health scores were 75 ± 6 and 89 ± 4, respectively. The median follow-up period was 36 months (range 6–126). During the first 3 years of follow-up, five high-risk patients with non-gastric GISTs developed recurrences. The 3-year overall survival rate was 100%, and the 3-year RFS rate was 92.8%, high-risk patients having a 3-year RFS rate of 89.8%. Conclusion:The adverse reactions and quality of life of GIST patients with severe adverse reactions to adjuvant imatinib therapy after complete resection can be mitigated by appropriately reducing the dosage of imatinib under the guidance of TDM.

[Objective]To investigate the impact of varying concentrations of baicalein on the proliferation and biological responses of MC3T3-E1 cells,as well as the antibacterial efficacy of baicalein against prevalent oral bacteria,and to elucidate the underlying mechanisms.[Methods]MC3T3-E1 cells were exposed to different concentrations of baicalein(0,6,12,18,and 24 μmol/L)and cell viability was determined by using the CCK-8 assay.Alkaline phosphatase(ALP)activity of MC3T3-E1 cells following osteogenic induction was assessed.RT-PCR was used to examine the expression of RunX2,BMP2,and Osterix.After 24 hours of treatment,the antibacterial potential of baicalein against Escherichia coli,Staphylococcus Aureus and Streptococcus Sanguis was evaluated by using the K-B paper disk method.[Results]Baicalein exhibited a modest reduction in proliferation of MC3T3-E1 cells but without affecting their sustained proliferation.Baicalein at a concentration of 18 μmol/L enhanced ALP activity of MC3T3-E1 cells,upregulated BMP2 and Osterix expression,downregulated RunX2 expression,significantly inhibited the proliferation of Staphylococcus Aureus and Streptococcus Sanguis(P<0.05).[Conclusions]Baicalein at an optimal concentration(18 μmol/L)demonstrated a promotional effect on the osteogenic differentiation of MC3T3-E1 cells and effectively suppressed the proliferation of common oral bacteria,including Staphylococcus Aureus and Streptococcus Sanguis.