Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE To explore the effects and potential mechanism of plumbagin on the inflammatory response and oxidative stress in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） based on Notch1/GATA3 signaling pathway. METHODS Ten rats were randomly selected as the control group； another 65 rats were used to establish the AECOPD model by inhaling cigarette smoke， intratracheal administration of endotoxin， and nasal inoculation of bacteria. The 50 successfully modeled rats were randomly divided into the AECOPD group， plumbagin low-dose group （10 mg/kg）， plumbagin high-dose group （50 mg/kg）， positive control group （dexamethasone 0.09 mg/kg）， and high-dose plumbagin+Jagged1 （Notch1 activator） group （50 mg/kg+25 mg/kg）， with 10 rats in each group. Each group was administrated intragastrically or intraperitoneally with the corresponding drug solution or normal saline， once a day for 28 consecutive days. After the last administration， the lung function indicators （peak expiratory flow， the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity）， the number of inflammatory cells （white blood cells， lymphocytes， neutrophils， macrophages） in bronchoalveolar lavage fluid， the levels of inflammatory factors [interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）] in lung tissue， and the contents of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in lung tissue were all determined in each group； the pathological changes of lung tissue and the pathological scores， as well as protein expressions of mucin 5ac （Muc5ac）， Notch1 and GATA3 in lung tissue were also detected. RESULTS Compared with the control group， the lung tissue of the AECOPD group rats showed severe damage to the alveolar wall structure， with a large number of inflammatory cells infiltration and accompanied by pathological changes such as thickening of the airway wall； their lung function indicators， IL-10 level， and SOD content were significantly decreased； while the number of various inflammatory cells， IL-6 and TNF-α levels， MDA content， pathological score， as well as protein expressions of Muc5ac， Notch1 and GATA3 were significantly increased or upregulated （P＜0.05）. Compared with the AECOPD group， the pathological changes in the lung tissue of the rats in each plumbagin dose group were significantly alleviated， and the above quantitative indicators were significantly improved， and the improvement was more obvious in the plumbagin high- dose group （P＜0.05）. Jagged1 significantly reversed the protective effect of high-dose plumbagin on lung injury and related indicators in AECOPD rats （P＜0.05）. CONCLUSIONS Plumbagin can inhibit the inflammatory response and oxidative stress in the lungs of AECOPD rats， alleviate lung damage， and improve lung function. The above effects may be related to the inhibition of the Notch1/GATA3 signaling pathway.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To construct and validate a predictive model for postoperative recurrence in early non-small cell lung cancer patients.Methods:The clinical data of 252 patients with early non-small cell lung cancer admitted to the 926th Hospital of Joint Logistic Support Force of PLA from January 2016 to January 2018were retrospectively collected. All of the patients underwent surgical treatment and they were followed up for 5 years after surgery, according the recurrence after surgery, they were divided into the recurrence group (103 cases) and non- recurrence group (149 cases). The risk factors for postoperative recurrence in early non-small cell lung cancer patients were analyzed. A predictive model for postoperative recurrence in early non-small cell lung cancer patients was constructed and validated.Results:The results of Logistic regression analysis showed that tumor long diameter≥ 3 cm, lymph node metastasis, low differentiation, spicules and pleural traction were independent risk factors for postoperative recurrence in early non-small cell lung cancer patients ( P<0.05). Using R4.0.3 statistical software, the dataset was randomly divided into a training set and a validation set, with a sample size of 176 cases in the training set and 76 cases in the validation set. A prediction model was constructed, with thearea under the curve (AUC) of the receiver operating characteristic (ROC) curve of 0.754 (95% CI 0.679 - 0.828) in the training set and AUC of 0.749 (95% CI 0.634 - 0.864) in the validation set. The model was subjected to a Hosmer-Lemeshow Goodness-of-Fit Test in the validation set, χ2 = 11.31, P = 0.185. Conclusions:The predictive model base on tumor long diameter ≥ 3 cm, lymph node metastasis, low differentiation, spicules and pleural traction can identify patients at high risk of postoperative recurrence in early non-small cell lung cancer effectively.

Objective To explore the mechanism of electroacupuncture in alleviating hyperlipidemia in a rat model by modulating mammalian target of rapamycin complex 1(mTORC1)-mediated lipophagy in hepatocytes.Methods A total of 30 SD rats were randomly divided into blank(n=6)and modeling groups(n=24)using the random number table method.A hyperlipidemic rat model was established by feeding rats a high-fat diet(feeding for 8 weeks).After successful modeling,the modeling group was randomly divided into the model,electroacupuncture,mTORC1 inhibitor,and electroacupuncture+mTORC1 agonist groups,with six rats in each group.Except for the blank group,all other rats were fed with high fat diet.Rats in the electroacupuncture and electroacupuncture+mTORC1 agonist groups received electroacupuncture intervention at bilateral"Fenglong"(ST40)acupoints(dilatational wave 2 Hz/100 Hz,current intensity 1 mA)for 30 min once daily.Rats in the mTORC1 inhibitor group received intraperitoneal injections of the mTORC1 inhibitor,rapamycin(2 mg/kg),once daily.Rats in the electroacupuncture+mTORC1 agonist group received intraperitoneal injections of the mTORC1 agonist MHY1485(10 mg/kg)once daily.The interventions were administered for five consecutive days per week for 4 weeks.Upon completion of the intervention,the following analyses were performed:serum contents of total cholesterol(TC),triglycerides(TAG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured using a fully automated biochemical analyzer.Hepatic histopathological changes and lipid deposition were observed using hematoxylin-eosin and oil red O staining.The liver condition was observed and the liver index was calculated.Hepatic TC and TAG levels were measured using an enzyme-linked immunosorbent assay.The ultrastructure of the liver tissue was observed using transmission electron microscopy,and the mean fluorescence intensity of perilipin 2(PLIN2)and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ in the liver tissue was detected using immunofluorescence.Protein expression of LC3-Ⅱ/LC3-Ⅰ,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and mTORC1 in liver tissue was detected using Western blotting.Results Compared to the blank group,the model group rats showed increased serum TC,TAG,LDL-C,ALT,AST,and FFA levels,along with decreased HDL-C levels(P<0.05).The liver index and hepatic TC and TAG levels were also elevated(P<0.05).Histological examination of liver tissue revealed substantial lipid accumulation,numerous lipid droplets within hepatocytes,abnormal mitochondrial morphology,and scarce autophagic vacuole.The mean fluorescence intensity of PLIN2 increased,whereas that of LC3-Ⅱ decreased(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio was reduced,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression were increased(P<0.05).Compared to the model group,rats in the mTORC1 inhibitor and electroacupuncture groups exhibited decreased serum TC,TAG,LDL-C,ALT,AST,and FFA levels(P<0.05),along with a reduced liver index and hepatic TC and TAG levels(P<0.05).Histological examination showed markedly attenuated lipid accumulation and visible autophagic vacuole in the hepatocytes.The mean fluorescence intensity of PLIN2 decreased,whereas that of LC3-Ⅱ increased(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio increased,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression decreased(P<0.05).In comparison with both the electroacupuncture and mTORC1 inhibitor groups,the electroacupuncture+mTORC1 agonist group demonstrated increased serum TAG,TC,LDL-C,ALT,AST,and FFA levels(P<0.05)as well as elevated liver index and hepatic TC and TAG levels(P<0.05).Liver tissues exhibited aggravated lipid deposition and absence of autophagic vacuole in liver cells.The mean fluorescence intensity of PLIN2 was enhanced,whereas that of LC3-Ⅱ was reduced(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio decreased,and the p-mTOR/mTOR ratio and mTORC1 protein expression increased(P<0.05).Conclusion Electroacupuncture at"Fenglong"(ST40)may improve blood lipid levels in hyperlipidemic rats by inhibiting mTORC1 and promoting hepatocyte lipophagy.

Objective To evaluate the reliability of Vitek 2 AST-N335 card for determining the susceptibility of Acinetobacter bauman-nii(AB)to cefoperazone/sulbactam.Methods A total of 318 non-repeated clinical isolates of AB collected in 2023 were tested for antimicrobial susceptibility to cefoperazone/sulbactam using broth microdilution(BMD),the AST-N335 card,and the Kirby-Bauer(K-B)disk diffusion method.Using BMD as the reference method,the reliability of AST-N335 card was assessed,and the accuracy of K-B disk diffusion method as the confirmatory test was validated.Results Compared with BMD,the susceptibility testing of 318 AB strains to cefoperazone/sulbactam using the AST-N335 card showed categorical agreement(CA)of 87.8％(279/318),very major er-ror(VME)of 6.0％(19/318),major error(ME)of 0％(0/318),and minor error(mE)of 1.9％(6/318),which fall outside of the acceptable error range.In contrast,the K-B method achieved CA of 99.4％(316/318),VME of 0％,ME of 0.3％(1/318),and mE of 0.3％(1/318),all within acceptable limits.Of these,the errors with AST-N335 card occurred within the minimum inhibitory concentration(MIC)range of 8-32 μg/mL.Using BMD as the reference method,further analysis was performed on the 171 AB strains with AST-N335 card MIC values of 8-32 μg/mL for cefoperazone/sulbactam.It was revealed that at MIC of 32 μg/mL,the CA was 0％;at MIC of 16 μg/mL,CA was 5.3％(1/19)and VME rate was 84.2％(16/19),both of which substantially exceeded accepta-ble error ranges.At MIC of 8 μg/mL,the CA was 94.9％(131/138)and VME was 2.2％(3/138),both approaching the acceptable ranges.Conclusion The results obtained with Vitek 2 AST-N335 card in determining for cefoperazone/sulbactam are unreliable when the MIC values fall within the range of 8-32 μg/mL,which leads to an underestimation of the resistance rate to cefoperazone/sulbac-tam.This issue requires urgent attention in both laboratories and clinical practice.The K-B disk diffusion method could serve as a sup-plementary verification approach in routine laboratories.

Objective:To analyze the mediating effects of psychological resilience on the relationship between perceived social support and health behavior capacity in patients with ischemic stroke.Methods:In this cross-sectional study, 500 patients with ischemic stroke were consecutively recruited using purposive sampling in the First People′s Hospital of Lianyungang between July and September in 2023. The sociodemographic characteristics, perceived social support scale, psychological resilience questionnaire and self-rated abilities for health practices scale in the patients were collected. A total of 500 questionnaires were distributed and 493 questionnaires were collected, of which 473 (95.9%) were valid. The structural equation model was constructed to explore the mediating effects of psychological resilience on the relationship between perceived social support and health behavior capacity in patients with ischemic stroke.Results:Among the 473 patients included in the analysis, there were 254 males and 219 females, with an average age of (66.8±11.4) years. The duration of stroke was less than 3 months for 329 patients (69.6%); the scores for perceived social support, psychological resilience and health behavior capacity was (59.68±11.15), (23.68±6.52), and (60.54±23.52), respectively. Perceived social support exerted significant direct effect ( β=0.334, bias-corrected 95% CI: 0.232-0.438) on health behavior capacity in patients with ischemic stroke, accounting for 63.62% of the total effect. Psychological resilience played a mediating role in the relationship between perceived social support and health behavior capacity ( β=0.191, bias-corrected 95% CI: 0.142-0.248), accounting for 36.38% of the total effect (all P<0.05). Conclusion:The health behavior capacity of patients with ischemic stroke is at a moderately low level, perceived social support may positively affect health behavior capacity through the positive mediating effect of psychological resilience.

Objective:To explore the clinical significance of skeletonized lymph node dissection of No.12 lymph nodes after neoadjuvant therapy in patients with advanced gastric cancer.Methods:For this retrospective case-cohort study we collected data from patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and D2 or more extensive curative resection including No.12 lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University from January, 2011 to December, 2022. Patients were divided into two groups based on whether they received skeletonized dissection of No.12 lymph nodes: 177 cases were in the skeletonized group, and 55 cases were in the nonskeletonized group. The differences of prognosis between the two groups were compared, and logistic regression models were used to analyze the factors affecting No.12 lymph node metastasis in the overall cohort and No.12b or No.12p lymph node metastasis in the skeletonized group.Results:A total of 232 patients were included, with 84 females (36.2%) and 148 males (63.8%), with an average age of 56.4±11.6 years. The proportion of female and ycT4 patients was significantly higher in the skeletonized group than in the nonskeletonized group (both P<0.05). Among all 232 patients, No. 12a metastasis occurred in 14 cases (6.0%). In the skeletonized group of 177 patients, No. 12b and No. 12p metastases were observed in 6 patients each (3.4%), and 4 patients had concurrent metastases in both No. 12b and No. 12a. The 5-year overall survival (OS) rates were 45.5% in the skeletonized group and 42.8% in the nonskeletonized group, with no statistical difference (HR=0.755, 95%CI: 0.488-1.168, P=0.580). The 5-year disease-free survival (DFS) rates were 39.8% and 41.0%, respectively, also with no statistical difference (HR=0.775, 95%CI: 0.513-1.172, P=0.584). 5-year OS for patients without No.12 lymph node metastasis was 48.8%, which was higher than the 15.9% for those with metastasis (HR=0.349, 95% CI: 0.209-0.584, P=0.003). Additionally, the 5-year DFS for those without metastasis was 44.3%, significantly higher than the 5.7% for those with metastasis (HR=0.444, 95%CI: 0.276-0.716, P<0.001). For patients without No. 12b or No. 12p lymph node metastasis, the 5-year OS was 47.6%, and the 5-year DFS was 42.3%, both of which were significantly higher than the 16.7% and 8.3% for those with No.12b or No. 12p lymph node metastasis, respectively (HR=0.353, 95%CI: 0.183-0.681, P=0.005; HR=0.457, 95%CI: 0.244-0.855, P=0.006). Multivariate analysis showed that more advanced ypN stage (OR=3.908, 95%CI:1.638-9.323, P=0.002) and tumor location in the lower stomach or whole stomach (OR=3.533, 95%CI: 1.312-9.511, P=0.012) were independent risk factors for No.12 lymph node metastasis and also for No.12b and No.12p lymph node metastasis (OR=2.426, 95%CI: 1.212-4.856, P=0.012 and OR=4.908, 95%CI:1.182-20.373, P=0.028, respectively). Conclusion:Patients with advanced gastric cancer who have more advanced ypN stage and tumor location in the lower stomach or whole stomach have a higher risk of No.12b and No.12p metastasis and thus require further skeletonized lymph node dissection of No.12.

Objective:To explore the clinical significance of skeletonized lymph node dissection of No.12 lymph nodes after neoadjuvant therapy in patients with advanced gastric cancer.Methods:For this retrospective case-cohort study we collected data from patients with advanced gastric cancer who underwent neoadjuvant chemotherapy and D2 or more extensive curative resection including No.12 lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University from January, 2011 to December, 2022. Patients were divided into two groups based on whether they received skeletonized dissection of No.12 lymph nodes: 177 cases were in the skeletonized group, and 55 cases were in the nonskeletonized group. The differences of prognosis between the two groups were compared, and logistic regression models were used to analyze the factors affecting No.12 lymph node metastasis in the overall cohort and No.12b or No.12p lymph node metastasis in the skeletonized group.Results:A total of 232 patients were included, with 84 females (36.2%) and 148 males (63.8%), with an average age of 56.4±11.6 years. The proportion of female and ycT4 patients was significantly higher in the skeletonized group than in the nonskeletonized group (both P<0.05). Among all 232 patients, No. 12a metastasis occurred in 14 cases (6.0%). In the skeletonized group of 177 patients, No. 12b and No. 12p metastases were observed in 6 patients each (3.4%), and 4 patients had concurrent metastases in both No. 12b and No. 12a. The 5-year overall survival (OS) rates were 45.5% in the skeletonized group and 42.8% in the nonskeletonized group, with no statistical difference (HR=0.755, 95%CI: 0.488-1.168, P=0.580). The 5-year disease-free survival (DFS) rates were 39.8% and 41.0%, respectively, also with no statistical difference (HR=0.775, 95%CI: 0.513-1.172, P=0.584). 5-year OS for patients without No.12 lymph node metastasis was 48.8%, which was higher than the 15.9% for those with metastasis (HR=0.349, 95% CI: 0.209-0.584, P=0.003). Additionally, the 5-year DFS for those without metastasis was 44.3%, significantly higher than the 5.7% for those with metastasis (HR=0.444, 95%CI: 0.276-0.716, P<0.001). For patients without No. 12b or No. 12p lymph node metastasis, the 5-year OS was 47.6%, and the 5-year DFS was 42.3%, both of which were significantly higher than the 16.7% and 8.3% for those with No.12b or No. 12p lymph node metastasis, respectively (HR=0.353, 95%CI: 0.183-0.681, P=0.005; HR=0.457, 95%CI: 0.244-0.855, P=0.006). Multivariate analysis showed that more advanced ypN stage (OR=3.908, 95%CI:1.638-9.323, P=0.002) and tumor location in the lower stomach or whole stomach (OR=3.533, 95%CI: 1.312-9.511, P=0.012) were independent risk factors for No.12 lymph node metastasis and also for No.12b and No.12p lymph node metastasis (OR=2.426, 95%CI: 1.212-4.856, P=0.012 and OR=4.908, 95%CI:1.182-20.373, P=0.028, respectively). Conclusion:Patients with advanced gastric cancer who have more advanced ypN stage and tumor location in the lower stomach or whole stomach have a higher risk of No.12b and No.12p metastasis and thus require further skeletonized lymph node dissection of No.12.