OBJECTIVE To explore the levels of helper T lymphocytes(Th)in patients with hepatitis B virus(HBV)infection who were treated with entecavir and observe the impact on viral clearance.METHODS A total of 149 patients with HBV infection who were treated with entecavir in Yan'an Hospital of Kunming City from Jan.2020 to Jan.2024 were enrolled in the study,82 of whom were chronic hepatitis B(CHB),and 67 were chro-nic hepatitis B virus carriers.The enrolled patients were divided into the clearance group with 64 cases and the no clearance group with 85 cases according to the levels of serum hepatitis B surface antigen(HBsAg)at Week 72 of the treatment.The clinical data were compared between the two groups,and the changes of Th1 and Th2 levels during the treatment were analyzed.Multivariate linear regression analysis was performed for the association be-tween virological change during the treatment and immune level.The risk factors for failed clearance of viruses were analyzed by logistic regression model.RESULTS There were significant differences in the age,the levels of alanine aminotransferase(ALT)and HBV DNA between the baseline and Week 24,the levels of aspartate trans-aminase(AST)at the baseline and Week 12,the HBsAg level at Week 24,and the baseline levels of Th1,Th1/Th2 between the CHBc treatment group and the CHB treatment group(P＜0.05).There were linear correlations between the HBV DNA,HBsAg,hepatitis E antigen(HBeAg)and the Th1,Th2 and Th1/Th2,respectively(P＜0.05).Totally 64 patients were accumulatively eradicated with HBsAg on Week 72,with the eradication rate 42.95％.After the confounding factors were adjusted,multivariate analysis showed that the high levels of Th1,Th2 and Th1/Th2 were the risk factors for the failed clearance of viruses(P＜0.05).CONCLUSIONS Among the patients with HBV infection,there is difference in the immune level between the CHB patients and the CHB virus carriers.The levels of Th1,Th2 and Th1/Th2 are strongly correlated with the HBV DNA,HBsAg,HBeAg and efficiency of viral clearance during the treatment with entecavir.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

OBJECTIVE To explore the levels of helper T lymphocytes(Th)in patients with hepatitis B virus(HBV)infection who were treated with entecavir and observe the impact on viral clearance.METHODS A total of 149 patients with HBV infection who were treated with entecavir in Yan'an Hospital of Kunming City from Jan.2020 to Jan.2024 were enrolled in the study,82 of whom were chronic hepatitis B(CHB),and 67 were chro-nic hepatitis B virus carriers.The enrolled patients were divided into the clearance group with 64 cases and the no clearance group with 85 cases according to the levels of serum hepatitis B surface antigen(HBsAg)at Week 72 of the treatment.The clinical data were compared between the two groups,and the changes of Th1 and Th2 levels during the treatment were analyzed.Multivariate linear regression analysis was performed for the association be-tween virological change during the treatment and immune level.The risk factors for failed clearance of viruses were analyzed by logistic regression model.RESULTS There were significant differences in the age,the levels of alanine aminotransferase(ALT)and HBV DNA between the baseline and Week 24,the levels of aspartate trans-aminase(AST)at the baseline and Week 12,the HBsAg level at Week 24,and the baseline levels of Th1,Th1/Th2 between the CHBc treatment group and the CHB treatment group(P＜0.05).There were linear correlations between the HBV DNA,HBsAg,hepatitis E antigen(HBeAg)and the Th1,Th2 and Th1/Th2,respectively(P＜0.05).Totally 64 patients were accumulatively eradicated with HBsAg on Week 72,with the eradication rate 42.95％.After the confounding factors were adjusted,multivariate analysis showed that the high levels of Th1,Th2 and Th1/Th2 were the risk factors for the failed clearance of viruses(P＜0.05).CONCLUSIONS Among the patients with HBV infection,there is difference in the immune level between the CHB patients and the CHB virus carriers.The levels of Th1,Th2 and Th1/Th2 are strongly correlated with the HBV DNA,HBsAg,HBeAg and efficiency of viral clearance during the treatment with entecavir.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Background:A large number of studies have confirmed that the combination therapy of high-dose proton pump inhibitor(PPI)and amoxicillin has a good efficacy for eradication of Helicobacter pylori(Hp).As a new high-efficiency acid inhibitor,vonoprazan is expected to improve the efficacy of Hp eradication and has a good application prospect.Aims:To compare the efficacy and safety of the dual therapy of vonoprazan-amoxicillin and bismuth-containing quadruple therapy,so as to provide new treatment idea and choice for Hp eradication therapy.Methods:This is a single-center,prospective,randomized controlled clinical trial.Two hundred and ten patients positive for Hp infection and naive to eradication therapy were recruited consecutively and randomly divided into two groups.One group received dual therapy of vonoprazan-amoxicillin:vonoprazan 20 mg bid and amoxicillin 1 g tid for 14 days;the other group received bismuth-containing quadruple therapy:rabeprazole 20 mg bid,potassium bismuth citrate 600 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid for 14 days.After 4-6 weeks of treatment completion,the Hp eradication rate(primary outcome)was evaluated by 14C-urea breath test.Safety and compliance(secondary outcomes)were also observed and recorded in the treatment course.Results:In intention-to-treat(ITT)analysis,the Hp eradication rate of dual therapy of vonoprazan-amoxicillin was 89.6%,and that of bismuth-containing quadruple therapy was 92.3%(P＞0.05).In per-protocol(PP)analysis,the eradication rates of these two groups were 90.5%and 94.1%,respectively(P＞0.05).The adverse events rate of dual therapy was significantly lower than that of the quadruple therapy(5.7%vs.20.2%,P＜0.05).Conclusions:The efficacy of 14-day dual therapy of vonoprazan-amoxicillin for initial eradication of Hp is equal to bismuth-containing quadruple therapy,with fewer adverse events and simpler medications.It can be considered as the first-line treatment scheme of empirical treatment of Hp infection.

Objective:To explore the teaching effect of combining diversified teaching modes with individualized teaching methods in musculoskeletal ultrasound training classes compared with traditional teaching modes.Methods:The 109 trainees participated in the muscle and bone ultrasound training classes from June 2020 to June 2022 were included as the research subjects and divided into the observation group ( n=53) and control group ( n=56). The control group received traditional teaching modes, while the observation group received diversified teaching modes in combination with individualized teaching methods. The differences in teaching satisfaction and final exam scores between the two groups were compared after training. Statistical analysis was conducted using the software SPSS 27.0. Categorical data were presented as cases and percentages, while continuous data were presented as mean±standard deviation. The intergroup differences in continuous variables were compared using the t-test, while the intergroup differences in categorical variables were compared using the chi-square test. Results:There were no significant differences in age, sex, education, and professional title between the control group and the observation group ( P>0.05). The comprehensive satisfaction score of ultrasound teaching was (88.08±6.65) in the observation group and (80.71±8.59) in the control group, with a significant difference between the two groups ( χ2=5.02, P<0.01). Before training, the test scores of the control group and the observation group were (62.61±5.39) and (63.87±7.77), respectively, and there was no significant difference between the two groups ( t=0.98, P=0.330). The final scores, theoretical exam, computer operation, and video reading exam scores of the control group were (84.07±1.49), (82.39±1.97), (85.13±2.55), and (86.79±6.06), respectively, while those of the observation group were (90.06±2.17), (88.28±3.19), (88.92±3.23), and (96.23±5.96); there were significant differences between the two groups in these four indicators ( t=16.75, 11.53, 6.79, and 8.20, respectively; P<0.01). The scores were compared for the two groups of trainees classified based on their unit level, professional title, and educational background. Trainees with the same unit level, professional title, and educational background showed no significant differences in test scores between the two groups, though their final scores were significantly different ( P<0.01). Conclusions:The combination of diversified teaching modes and individualized teaching methods can increase the learning enthusiasm of trainees, improve the teaching effect of training classes, and increase the satisfaction of trainees.

ObjectiveTo construct a cough model induced by chemical stimuli by whole-body plethysmography （WBP） for counting coughs based on cough waveforms， and use this model to explore the antitussive effect of GK-A. MethodDifferent chemical stimuli were used to induce coughs in mice or guinea pigs. Respiratory waveforms were monitored by WBP， and the recognizable and typical cough waveforms were selected for cough counting. Guinea pigs were induced to cough with different concentrations of citric acid or capsaicin， and cough waveforms were used to optimize the stimulation conditions. The optimized guinea pig model of cough was validated with dextromethorphan， and the optimized guinea pig model of capsaicin-induced cough was used to evaluate the antitussive effect of GK-A. ResultWBP could count the coughs induced by capsaicin and citric acid in guinea pigs by recognizable and typical respiratory waveforms. The optimized stimulation conditions were capsaicin concentration of 100 µmol·L^-1 and nebulization for 2 min. The validation results showed that compared with the model group， the dextromethorphan group of guinea pigs had reduced coughs （P<0.05） and prolonged cough latency （P<0.01）. GK-A prolonged the cough latency （P<0.05） and reduced coughs （P<0.05） in the mouse model of ammonia-induced cough. In the guinea pig model of capsaicin-induced cough， GK-A prolonged cough latency （P<0.05）， reduced coughs （P<0.05）， and decreased substance P （SP） content in the guinea pig serum （P<0.05， P<0.01）. ConclusionA guinea pig model of capsaicin-induced cough was successfully established based on cough waveform counting， which provided an objective and accurate cough counting method. GK-A has antitussive effects， possibly by inhibiting the neuropeptide SP.

Background:A large number of studies have confirmed that the combination therapy of high-dose proton pump inhibitor(PPI)and amoxicillin has a good efficacy for eradication of Helicobacter pylori(Hp).As a new high-efficiency acid inhibitor,vonoprazan is expected to improve the efficacy of Hp eradication and has a good application prospect.Aims:To compare the efficacy and safety of the dual therapy of vonoprazan-amoxicillin and bismuth-containing quadruple therapy,so as to provide new treatment idea and choice for Hp eradication therapy.Methods:This is a single-center,prospective,randomized controlled clinical trial.Two hundred and ten patients positive for Hp infection and naive to eradication therapy were recruited consecutively and randomly divided into two groups.One group received dual therapy of vonoprazan-amoxicillin:vonoprazan 20 mg bid and amoxicillin 1 g tid for 14 days;the other group received bismuth-containing quadruple therapy:rabeprazole 20 mg bid,potassium bismuth citrate 600 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid for 14 days.After 4-6 weeks of treatment completion,the Hp eradication rate(primary outcome)was evaluated by 14C-urea breath test.Safety and compliance(secondary outcomes)were also observed and recorded in the treatment course.Results:In intention-to-treat(ITT)analysis,the Hp eradication rate of dual therapy of vonoprazan-amoxicillin was 89.6%,and that of bismuth-containing quadruple therapy was 92.3%(P＞0.05).In per-protocol(PP)analysis,the eradication rates of these two groups were 90.5%and 94.1%,respectively(P＞0.05).The adverse events rate of dual therapy was significantly lower than that of the quadruple therapy(5.7%vs.20.2%,P＜0.05).Conclusions:The efficacy of 14-day dual therapy of vonoprazan-amoxicillin for initial eradication of Hp is equal to bismuth-containing quadruple therapy,with fewer adverse events and simpler medications.It can be considered as the first-line treatment scheme of empirical treatment of Hp infection.

BACKGROUND: The SMARCA4 mutation has been shown to account for at least 10% of non-small cell lung cancer (NSCLC). In the present, conventional radiotherapy and targeted therapy are difficult to improve outcomes due to the highly aggressive and refractory nature of SMARCA4-deficient NSCLC (SMARCA4-DNSCLC) and the absence of sensitive site mutations for targeted drug therapy, and chemotherapy combined with or without immunotherapy is the main treatment. Effective SMARCA4-DNSCLC therapeutic options, however, are still debatable. Our study aimed to investigate the efficacy and prognosis of programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in combination with chemotherapy and chemotherapy in patients with stage III-IV SMARCA4-DNSCLC. METHODS: 46 patients with stage III-IV SMARCA4-DNSCLC were divided into two groups based on their treatment regimen: the chemotherapy group and the PD-1 ICIs plus chemotherapy group, and their clinical data were retrospectively analyzed. Efficacy assessment and survival analysis were performed in both groups, and the influencing factors for prognosis were explored for patients with SMARCA4-DNSCLC. RESULTS: Male smokers are more likely to develop SMARCA4-DNSCLC. There was no significant difference in the objective response rate (76.5% vs 69.0%, P=0.836) between chemotherapy and the PD-1 ICIs plus chemotherapy or the disease control rate (100.0% vs 89.7%, P=0.286). The one-year overall survival rate in the group with PD-1 ICIs plus chemotherapy was 62.7%, and that of the chemotherapy group was 46.0%. The difference in median progression-free survival (PFS) between the PD-1 ICIs plus chemotherapy group and the chemotherapy group was statistically significant (9.3 mon vs 6.1 mon, P=0.048). The results of Cox regression analysis showed that treatment regimen and smoking history were independent influencing factors of PFS in patients with stage III-IV SMARCA4-DNSCLC, and family history was an individual influencing factor of overall survival in patients with stage III-IV SMARCA4-DNSCLC. CONCLUSIONS Treatment regimen may be a prognostic factor for patients with SMARCA4-DNSCLC, and patients with PD-1 ICIs plus chemotherapy may have a better prognosis.
Humans ; Male ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Programmed Cell Death 1 Receptor/genetics* ; Retrospective Studies ; Antineoplastic Agents, Immunological/therapeutic use* ; Prognosis ; DNA Helicases/genetics* ; Nuclear Proteins/genetics* ; Transcription Factors/genetics*

Objective To investigate the effect of Liu-Shen-Wan on transplanted tumors in mice with colon cancer based on the polarization of M2 macrophages in the tumor microenvironment. Methods We established a subcutaneous transplantation tumor model of mice with CT26 colon cancer. Mice were randomly divided into vehicle, oxaliplatin, and oxaliplatin combined with Liu-Shen-Wan groups. Treatment was administered for three weeks, and tumor volume was measured. All mice were weighed during the administration. After the end of the treatment, the mice were dissected and tumors were photographed and weighed. Spleen index was calculated. The expression levels of IFN-γ and IL-12P40 in serum and related blood biochemical indices were measured. The expression levels of M2 macrophage polarization indices, namely, IL-10 and TGF-β, in serum and tumor tissues were detected. The infiltration degree of M2 macrophages in each group was observed by immunohistochemical experiments. Results The tumor volume and mouse weight in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased compared with those in the vehicle group. The spleen index increased, and the expression levels of IFN-γ and IL-12P40 in serum also significantly increased. The mice had no obvious side effects after the drug treatment. In addition, the expression levels of IL-10 and TGF-β in the serum and tissues of mice in the oxaliplatin combined with Liu-Shen-Wan group significantly decreased. The expression levels of CD68 and CD206 in tumor tissues also decreased. Conclusion The anti-tumor effect of Liu-Shen-Wan on the transplanted tumors of mice with colon cancer is related to the inhibition of M2 macrophage polarization in the tumor microenvironment.