To systematically synthesize evidence on multiple KRAS G12C inhibitors(KRAS G12C inhibitors, KRAS G12Ci) as monotherapy within a unified population and recommended-dose framework, establish a comparable benchmark range of efficacy and safety for previously treated patients with advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC), and explore potential effect modifiers.

Objective:To explore the impact of a three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women.Methods:It was a randomized controlled trial. A simple random sampling method was used to select 460 singleton pregnant women with a pre-pregnancy body mass index≥24 kg/m2 who had regular prenatal check-ups at the Obstetrics and Gynecology Center of the Third Affiliated Hospital of Chongqing Medical University from June 1, 2018, to December 31, 2022. The women were randomly divided into an experimental group and a control group (230 cases each) using a computer-generated random number table. The control group received regular prenatal check-ups according to the pregnancy care guidelines (once every 4 weeks during mid-pregnancy, once every 2 weeks during late pregnancy, with additional frequency as needed based on the condition). The control group also received a one-time body composition analysis and dietary guidance from a nutritionist at the time of registration. In addition to the control group′s interventions, the experimental group received three-dimensional management based on a perinatal one-day clinic. It included an intensive one-day clinic session, a traditional plus internet-based re-education model (as needed based on the condition), individualized guidance from obstetrics and clinical nutrition clinics (once every 2 weeks), a free body composition test at 24 weeks of pregnancy, and weekly WeChat group push of health care knowledge during pregnancy. A total of 55 cases dropped out, leaving 200 cases in the experimental group and 205 cases in the control group for analysis. General information, pregnancy-related, and postpartum indicators were collected in the two groups. The effect of three-dimensional management based on a perinatal one-day clinic on pregnancy outcomes in overweight and obese pregnant women was analyzed using t-tests and chi-square tests. Results:There was no significant differences in baseline age, pre-pregnancy body mass index, initial blood glucose, initial glycated hemoglobin, or initial gestational age between the two groups (all P>0.05). The experimental group showed significantly lower gestational weight gain, neonatal weight, and proportion of excessive pregnancy weight gain compared to those in the control group [(11.41±5.23) vs (13.22±4.51) kg, (3 352.1±465.3) vs (3 489.5±464.0) g, 48.00% vs 73.17%] (all P<0.05). There were no significant differences in hospitalization days, gestational age at delivery, incidence of gestational diabetes, incidence of hypertensive disorders of pregnancy, incidence of premature rupture of membranes, incidence of preterm birth, incidence of macrosomia, vaginal delivery rate and rate of neonatal transfer to the pediatric department between the two groups (all P>0.05). Conclusion:Early intervention with the three-dimensional management based on the one-day perinatal clinic can effectively control gestational weight gain and neonatal weight in overweight and obese pregnant women.

Objective:To preliminarily explore therapeutic effects and possible molecular mechanisms of sinomenine on atopic dermatitis (AD) -like mouse models.Methods:Thirty female BALB/c mice (6 - 8 weeks old) were randomly divided into 5 groups: blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group. Except for the blank control group, all groups were subjected to repeated topical stimulation with 2,4-dinitrochlorobenzene (DNCB) on the dorsal skin to establish an AD-like mouse model. After modeling, no special treatment was given to the blank control group, the positive control group was topically treated with 100 μg of 0.1% mometasone furoate cream twice daily on the lesions, the topical sinomenine group was topically treated with 100 μl of 10 mg/ml sinomenine solution twice daily on the lesions, and the oral sinomenine group was gavaged with sinomenine solution at a dose of 100 mg·kg -1·d -1 (100 μl per dose, twice daily) . Treatments lasted for 14 days. Twelve hours after the final treatment, the severity of skin lesions in each group was assessed. Blood samples were collected via enucleation, and serum levels of interleukin (IL) -1β, IL-6, and immunoglobulin E (IgE) were measured using enzyme-linked immunosorbent assay (ELISA) . Histopathological changes in dorsal skin lesions were observed, and immunohistochemical study was performed to detect the expression levels of p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF) -κB p65 in skin tissues, expressed as the percentage of the immunopositive area. One-way analysis of variance was used for multiple group comparisons, while Tukey′s test or the Games-Howell test was applied for post-hoc comparisons between groups. Results:Compared with the blank control group, the model group exhibited epidermal hyperkeratosis with parakeratosis, thickening of the spinous layer, spongiosis, significant inflammatory cell infiltration, and prominent angiogenesis. In contrast, the positive control group, topical sinomenine group, and oral sinomenine group showed reduced spinous layer thicknesses, decreased inflammatory cell infiltration, and less pronounced angiogenesis compared to the model group. In the blank control group, model group, positive control group, topical sinomenine group, and oral sinomenine group, the severity scores of skin lesions were 0, 8.83 ± 0.75, 4.33 ± 1.08, 2.58 ± 0.49, 2.83 ± 0.93 respectively, the serum levels of IL-1β were 52.58 ± 1.72, 168.40 ± 7.23, 57.07 ± 6.39, 85.74 ± 4.15, 100.30 ± 11.55 pg/ml respectively, IL-6 levels were 86.88 ± 4.60, 215.00 ± 5.02, 79.34 ± 4.91, 127.20 ± 1.06, 149.00 ± 6.21 pg/ml respectively, IgE levels were 2 159.00 ± 176.00, 3 493.00 ± 89.61, 2 294.00 ± 158.10, 2 550.00 ± 214.70, 2 814.00 ± 119.70 μg/ml respectively, the expression levels of p38 MAPK in skin tissues were 3.03% ± 3.38%, 12.95% ± 6.89%, 2.14% ± 1.28%, 5.28% ± 3.71%, 3.85% ± 2.26% respectively, and NF-κB p65 expression levels were 0.61% ± 0.49%, 18.92% ± 6.96%, 3.77% ± 1.90%, 5.66% ± 2.28%, 6.25% ± 3.14% respectively; the differences in all the above parameters were statistically significant among groups (all P < 0.05) . Compared with the blank control group, the model group had significantly increased skin lesion severity scores, serum IL-1β, IL-6, and IgE levels, as well as elevated expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.01) . Compared with the model group, the positive control group, topical sinomenine group, and oral sinomenine group showed significantly reduced skin lesion severity scores, decreased serum IL-1β, IL-6, and IgE levels, and lower expression of p38 MAPK and NF-κB p65 in skin tissues (all P < 0.05) . Compared with the positive control group, the topical and oral sinomenine groups exhibited further reductions in skin lesion severity scores (both P < 0.05) . Additionally, the topical sinomenine group showed significantly lower serum levels of IL-1β and IL-6 compared with the oral sinomenine group (both P < 0.05) . Conclusion:Sinomenine solution could obviously alleviate the severity of skin lesions in AD-like mouse models, likely by down-regulating the expression of IL-1β, IL-6 and IgE, inhibiting the MAPK/NF-κB signaling pathway, and thus reducing the degree of inflammation.

OBJECTIVES: To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone (DMQ) for alleviating dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. METHODS: Eighteen male C57BL/6J mice were equally randomized into control group, DSS group and DMQ treatment group. In DSS and DMQ groups, the mice were treated with DSS in drinking water to induce UC, and received intraperitoneal injections of sterile PBS or DMQ (20 mg/kg) during modeling. The changes in body weight, disease activity index (DAI), colon length, spleen weight, and colon histological scores of the mice were examined, and the percentages of Th17 and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry. The expressions of tight junction proteins (Occludin and ZO-1), proteins associated with inflammasome activation (caspase-1 and p20), IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA. In the cell experiment, mouse bone marrow-derived macrophages (BMDMs) primed with lipopolysaccharide (LPS) were treated with DMQ, followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway. In cultured human peripheral blood mononuclear cells (PBMCs) treated with either LPS alone or LPS plus nigericin, the effects of DMQ on inflammasome activation, pyroptosis, and cytokine release were evaluated via Western blotting, ELISA, and flow cytometry. RESULTS: In DSS-treated mice, DMQ treatment significantly alleviated DSS-induced body weight loss, colon shortening, spleen enlargement, and colon inflammation. The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ⁺ CD8⁺ T cells in the mesenteric lymph nodes and spleen, with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue. DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs, causing also suppression of caspase-1-dependent pyroptosis. CONCLUSIONS DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Colitis, Ulcerative/metabolism* ; Dextran Sulfate/adverse effects* ; Male ; Inflammasomes/metabolism* ; Mice ; Benzoquinones/therapeutic use* ; Th17 Cells ; Caspase 1/metabolism*

Objective:This study investigated the awareness and consumption of Trogia venenata among populations in regions affected by Yunnan unexplained sudden death (YUSD). The findings aim to support etiological research on YUSD and contribute to the formulation of preventive measures against Trogia venenata poisoning. Methods:This study was a case-control study. From 2018 to 2021, surveys were conducted in 90 villages across 25 counties within YUSD-affected areas in Yunnan Province. Households with YUSD cases were designated as case households, whereas households without YUSD cases served as controls, ande were selected through convenience sampling at a 3:1 ratio. An enhanced questionnaire was designed to collect information on the consumption of Trogia venenata, and symptoms following consumption. Frequency data were presented as percentages, and group comparisons were conducted using χ 2 tests or Fisher’s exact tests. Results:A total of 711 questionnaires were collected (response rate: 100%), comprising 175 case households and 536 control households. Trogia venenata was present in 80.82% of the villages surveyed. Among the 711 households, 15.89% reported consuming Trogia venenata, primarily through stir-frying (53.10%), followed by boiling (29.20%), boiling and stir-frying (15.93%), and steaming (1.77%). Most households (94.69%) consumed fresh fruiting bodies, with 69.02% consuming them fewer than three times annually. The consumption rates were higher among the case households than among the control households. Of the 113 households with a history of Trogia venenata consumption, 35.40% reported symptoms such as nausea, vomiting, and limb soreness. The proportions of affected families in each group were compared according to their source, cooking method, fruiting body status and consumption frequency. The proportion of affected families with high consumption frequency (≥3 times/year) was higher than that with low consumption frequency (<3 times/year). Among 421 YUSD cases, 63 cases (14.96%) had a history of Trogia venenata consumption before death, with 43 cases showing symptoms within the longest known latency period (14 d) for poisoning by this mushroom. Conclusions:Trogia venenata is prevalent in 80.82% of YUSD-affected regions, with 16.67% of the population reporting its consumption, predominantly as fresh fruiting bodies prepared by stir-frying or boiling. Confirmed Trogia venenata consumption was identified in 14.96% of YUSD cases, suggesting that mushroom poisoning is a significant risk factor for YUSD. Ongoing health education and interventions are critical for mitigating the risk of Trogia venenata poisoning.

Objective To explore the factors associated with respiratory syncytial virus(RSV)infection in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and its correlation with serum levels of heat shock protein 70(HSP70),Krüppel-like factor 5(KLF5),and macrophage inflammatory protein-2(MIP-2).Methods A total of 195 AECOPD patients were prospectively enrolled and categorized into an RSV-infected group(n=95)and an uninfected group(n=100)based on RSV infection status.The infected group was further subdivided by disease severity into mild,moderate,and severe subgroups(31 cases,35 cases,29 cases),and by prognosis into poor prognosis(n=51)and good prognosis subgroups(n=44).ELISA method was used to measure the serum levels of HSP70,KLF5,and MIP-2 in each group,and their correlation with relevant clinical indicators was analyzed.Multivariate Cox regression analysis was used to explore risk factors for RSV infection in AECOPD patients.Relative risk analysis was used to explore the impact of high and low levels of HSP70,KLF5,and MIP-2 on the prognosis of AECOPD patients with RSV infection.Kaplan-Meier survival curves analyzed patient survival outcomes.Receiver operating characteristic(ROC)curves were plotted to analyze the predictive value of serum HSP70,KLF5,and MIP-2 levels for the prognosis of AECOPD patients with RSV infection.Results The infected group had significantly higher proportions of respiratory failure,higher number of exacerbations within one year,and higher levels of CRP,HSP70,KLF5,and MIP-2 compared to the non-infected group(P<0.05),while FEV1%pred were significantly lower(P<0.05).Serum HSP70,KLF5,MIP-2 levels were positively correlated with respiratory failure,number of exacerbations within one year,and CRP levels(P<0.05),and negatively correlated with FEV1%pred(P<0.05).Multivariate Cox regression identified respiratory failure,number of AECOPD exacerbations within one year≥3 times,low FEV1%pred,and high levels of CRP,HSP70,KLF5,and MIP-2 as independent risk factors for RSV infection in AECOPD patients(P<0.05).As the condition worsens,the levels of serum HSP70,KLF5,and MIP-2 gradually increase(P<0.05).The poor prognosis subgroup had prominently higher serum levels than the good prognosis subgroup(P<0.05).Patients with high levels of HSP70,KLF5,and MIP-2 have a greater risk of poor prognosis and a lower 28-day progression-free survival rate(P<0.05).The areas under the ROC curve(AUC)predicted by the combination of the three indicators was significantly better than that predicted by a single indicator(P=0.015).Conclusion Respiratory failure,the number of AECOPD exacerbations within one year≥3 times,low FEV1%pred,high CRP level,and high serum levels of HSP70,KLF5,and MIP-2 are risk factors for RSV infection in AECOPD patients.Serum levels of HSP70,KLF5,MIP-2 are closely related to disease severity and prognosis in AECOPD patients with RSV infection.The combined detection of the three biomarkers has significant predictive value for patient prognosis,which is helpful for early clinical assessment and the formulation of intervention strategies.

Objective To investigate the value of integrin subunit αM(ITGAM)and integrin subunit β2(ITGB2)levels in peripheral blood mononuclear cells(PBMC)in the diagnosis and prognosis evaluation for patients with severe acute pancreatitis(SAP)complicated with acute lung injury(ALI).Methods A total of 205 patients with SAP admitted from November 2022 to February 2024 in the hospital were selected,and they were divided into ALI group(103 cases)and non-ALI group(102 cases)according to whether they were com-plicated with ALI.Meanwhile,110 healthy people who underwent the physical examination were selected as the control group.The differences of the levels of ITGAM and ITGB2 in PBMC in different groups were com-pared.Logistic regression was used to analyze the influencing factors for ALI in patients with SAP.The re-ceiver operating characteristic(ROC)curve was used to analyze the diagnostic value of levels of ITGAM and ITGB2 in PBMC for SAP patients complicated with ALI and the predictive value for poor prognosis.Results The levels of ITGAM,ITGB2 in PBMC,and serum amylase and urine amylase levels in ALI group were higher than those in non-ALI group and control group(P＜0.05).Multivariate Logistic regression anal-ysis showed that the increase of ITGAM,ITGB2 and serum amylase levels were risk factors for ALI in pa-tients with SAP(P＜0.05).ROC curve results showed that the area under the curve(AUC)of ITGAM com-bined with ITGB2 in diagnosing ALI in patients with SAP was significantly higher than those of ITGAM and ITGB2 alone(P＜0.05).The levels of ITGAM and ITGB2 in PBMC in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).ROC curve results showed that the AUC of ITGAM com-bined with ITGB2 in predicting poor prognosis in patients with SAP complicated with ALI was significantly higher than those of ITGAM and ITGB2 alone(P＜0.05).Conclusion Increased levels of ITGAM and IT-GB2 in PBMC are risk factors for ALI in patients with SAP.ITGAM combined with ITGB2 has a good predic-tive efficacy for the poor prognosis in patients with SAP complicated with ALI,which has important value in clinical practice and is expected to become potential biomarkers.

Objective To explore the protective effect of 7,8-dihydroxyflavone(7,8-DHF)on the retina of diabetic rats and its mechanism.Methods A total of 18 SPF-grade male Sprague-Dawley(SD)rats were selected and randomly divided into three groups:the normal group,the model group,and the experimental group,with six rats in each group.Rats in the normal group were fed with a normal diet,while those in the remaining two groups were fed with a high-fat emulsion through oral gavage continuously for 2 weeks to establish a diabetes model.Rats in the experimental group were provided with 7,8-DHF(5 mg?kg-1)by continuous intraperitoneal injection,while those in the normal and model groups were provided with an equal volume of normal saline.The rats in all groups received intervention once a day for 2 weeks.The changes in the body mass and fasting blood glucose(FBG)were observed before and after modeling.Besides,the changes in the retina of rats in each group were observed by fundus fluorescence angiography(FFA)after 2 weeks.Moreo-ver,the changes and apoptosis of retinal neuronal cells were detected by hematoxylin and eosin(HE)staining,CD31 im-munofluorescence,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assays.Results After 2 weeks of continuous intervention,compared with the normal group,the body mass of rats in the model and experimental groups decreased(both P＜0.05),and the FBG increased significantly(both P＜0.05);compared with the model group,the experimental group showed an increase in the body mass(P＜0.05)and a decrease in the FBG(P＜0.05).The fundus photography and FFA of rats in the three groups did not reveal any fundus features of diabetic retinopathy.The HE staining results showed that the retina of rats in the normal and experimental groups was structurally intact,with neatly arranged cells and uniform thickness;the retinal structure of rats in the model group remained clear.However,the thickness of the inner layers of the retina of rats in the model group was thinner compared with the normal and experimental groups,exhibi-ting significant differences(both P＜0.05).The CD31 immunofluorescence assay results indicated that the CD31 immuno-fluorescence intensity values of rats in the three groups were roughly comparable,without significant differences(all P＞0.05).The TUNEL assay results suggested that the apoptosis of retinal neurons increased in rats in the model group com-pared with the normal group,exhibiting significant differences(P＜0.001);compared with the model group,the apoptosis of retinal neurons of rats in the experimental group decreased significantly,displaying significant differences(P＜0.001).Conclusion The apoptosis of retinal neurons in diabetic rats may precede vascular endothelial cell injury.7,8-DHF can improve the body mass,decrease the blood glucose level,and protect the retinal neurons in diabetic rats.

Pregnancy with chronic kidney disease (CKD), particularly in stages 4-5, carries high risks of adverse outcomes including maternal renal failure, preeclampsia/eclampsia, fetal growth restriction, and preterm birth. This report described a 26-year-old woman with congenital solitary kidney, polycystic ovaries, and uterine septum due to PAX2 gene variant, complicated by CKD stage 4. Through multidisciplinary team precision management and individualized treatment strategies, including timely initiation of dialysis, the patient successfully maintained pregnancy until 34 +1 weeks and delivered a female infant via cesarean section. This case summarizes key management experiences for end-stage renal disease in pregnancy, highlighting early risk assessment, precise nutritional management, hemodialysis protocol optimization, and the crucial role of multidisciplinary collaboration, providing valuable references for managing CKD-complicated pregnancies.

Objective:To investigate impact of leonurine(Leo)on necrotic apoptosis in rats with myocardial ischemia/reperfu-sion(MIR)injury by regulating receptor interacting protein 1(RIP1)-receptor interacting protein 3(RIP3)-mixed lineage kinase domain-like protein(MLKL)pathway.Methods:Fifteen rats were randomly selected as sham surgery group(Sham),left anterior descending coronary artery of remaining rats were ligated to construct MIR model,and randomly grouped into MIR group,Leo group(15 mg/kg),Compound 6i group(1 mg/kg RIP1-RIP3-MLKL pathway activator Compound 6i)and Leo+Compound 6i group(15 mg/kg Leo+1 mg/kg Compound 6i),with 15 rats in each group.MIR group and Sham group were injected with equal amounts of physiological saline.Cardiac function indicators were observed through ultrasound electrocardiogram;ELISA was applied to detect myocardial injury indicators and inflammatory factor levels;HE staining was applied to observe pathological damage of heart;TTC staining was applied to detect myocardial infarction area;TUNEL staining was applied to detect cell apoptosis;Western blot was applied to detect expres-sions of RIP1-RIP3-MLKL pathway proteins.Results:Myocardial cells in Sham group were intact and arranged in an orderly manner;arrangement of myocardial cells was disordered and swollen,myofibril contracted,and sarcolemma was destroyed in MIR group,ejec-tion fraction(EF)and cardiac output(CO)level were obviously lower than Sham group(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously increased(P<0.05);compared with MIR group,Leo group had improved cell arrangement disorder and edema,and obviously increased EF and CO levels(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously reduced(P<0.05),trend of Compound 6i group was opposite;myocardial tissue structure of Leo+Compound 6i group was similar to MIR group,and Compound 6i eliminated cardioprotective effect of Leo on MIR rats.Conclusion:Leo may alleviate myocardial necrosis apoptosis in MIR rats by down-regulating RIP1-RIP3-MLKL pathway,thus playing a therapeutic role in MIR.