ObjectiveTo investigate the efficacy and safety of Babaodan Capsule （BBD） in the treatment of patients with chronic hepatitis B virus （HBV） infection with damp-heat in the liver and gallbladder comorbid with gallbladder polyps. MethodsA randomized， double-blinded， placebo-controlled single-center trial was conducted among 120 patients with chronic HBV infection who were admitted to Beijing YouAn Hospital， Capital Medical University， from August 2020 to April 2023， and they were divided into treatment group （BBD） and control group （placebo）， with 60 patients in each group. The course of treatment was 24 weeks， and follow-up assessments were conducted every 4 weeks. The primary outcome measures were the number and maximum diameter of gallbladder polyps （assessed by ultrasound）， and the secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， blood lipid levels， and liver function parameters. The independent-samples t test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups； the Wilcoxon rank-sum test was used for comparison of ranked data between two groups； the generalized estimating equation was used to analyze repeated measures data. ResultsAfter 8 weeks of treatment， the treatment group had a significantly smaller diameter of polyps and a significantly lower number of polyps than the control group （Z=-1.76 and -1.80， both P<0.05）， and after 24 weeks of treatment， the treatment group had a significantly higher polyp reduction rate than the control group （30.51% vs 10.91%， P<0.05）. The subgroup analysis showed that patients receiving combined antiviral therapy， male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps tended to achieve significantly greater benefits. At week 8 of treatment， the treatment group had a significantly better TCM syndrome score than the control group （Z=-2.35， P<0.05）； after treatment， compared with the control group， the treatment group had a significantly greater increase in high-density lipoprotein （Z=-1.85， P<0.05） and significantly lower levels of alanine aminotransferase （Z=-2.06， P <0.05）， aspartate aminotransferase （Z=-2.13， P<0.05）， total bilirubin （Z=-2.12， P<0.05）， and direct bilirubin （Z=-3.09， P<0.05）. No serious adverse events were reported in either group. ConclusionBBD can effectively reduce the size of gallbladder polyps， improve TCM syndrome score， and reduce the level of bilirubin in patients with chronic HBV infection with damp-heat in the liver and gallbladder， with a favorable safety profile， and it may be more suitable for patients receiving combined antiviral therapy and specific subgroups （male patients， patients with a diameter of polyps of <5 mm， and patients with multiple polyps.

The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

Objective To investigate the changes of macrophages and hemophagocytes in bone marrow smears of patients with multiple myeloma(MM)before and after chemotherapy and their correlation with clinical prognostic value.Methods A total of 300 MM patients treated in Liaocheng Second People's Hospital Affiliated to Shandong First Medical University from June 2018 to June 2023 were selected as the study objects.All patients received at least 3 courses of chemotherapy and were divided into the remission group(n=214)and the non-remission group(n=86)according to the clinical effect.Immunoglobulin(Ig)A,IgG,CD3+,CD4+,CD8+,interleukin(IL-2),IL-4,IL-6,IL-17,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,macrophages and hemophagocytes were detected in the two groups and compared between the two groups.COX regression was used to analyze the relationship between immunological indexes and non-remission of chemotherapy.The relationship between macrophages and hemophagocytes and non-remission of chemotherapy was analyzed by restricted cubic spline.The multiplicative interaction of macrophages and hemophagocytes on non-remission of chemotherapy was analyzed using an unconditioned Logistic regression model,and the additive interaction was analyzed using the interaction calculation table.Receiver operating characteristic(ROC)curve analysis of macrophages and hemophagocytes alone or in combination to determine the value of chemotherapy non-remission.Results The overall response rate(ORR)and non-response rate(NRR)of MM patients were 71.33%and 28.67%respectively.Compared with before treatment,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes were significantly decreased in both groups after treatment(tslow=9.252～61.177,tnot slow=4.057～35.797).CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly increased(tslow=9.706～33.940,tnot slow=4.227～16.167),and the differences were statistically significant(all P<0.05).After treatment,compared with the remission group,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes in the non-remission group were significantly higher than those in remission group(t=3.362～30.028),CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly lower than those in remission group(t=3.736～13.998).and the differences were statistically significant(all P＜0.05).After adjusting the influence of other factors by COX regression,the trend test of macrophages and hemophagocytes was still statistically significant the trend test of macrophages and hemophagocytes was still statistically significant(P<0.05).Patients with≥5 macrophages/tablet and≥3 hemophagocytes/tablet had a significantly increased risk of non-remission from chemotherapy(P<0.05).There were additive(OR=6.157,95%CI:3.768～12.978)and multiplicative(OR=5.648,95%CI:1.035～17.492)interactions between macrophages and hemophagocytes in the non-remission of chemotherapy.Compared with the single judgment of macrophages and hemophagocytes,the combination of the two has the highest accuracy in determining chemotherapy non-remission(P＜0.05).Conclusion Macrophages and hemophagocytic cells in MM patients after chemotherapy are significantly lower than those before chemotherapy,with≥5 macrophages/tablet and≥3 hemocyte phages/tablet,indicating that the risk of non-remission in patients with chemotherapy increased significantly,and the combination of the two can accurately judge the clinical efficacy.

Objective Maternal-and-child health(MCH)hospitals simultaneously provide clinical care and manage community-based public-health projects for women and children.We aimed to design and test a performance-based salary and e-valuation system that recognizes this dual responsibility and incentivizes high-quality public-health work.Methods Aligned with the national tertiary-level MCH-hospital performance appraisal standards and local project realities,we applied four industrial-en-gineering techniques—empirical time-and-motion estimation,classification,analogy and work-study—to convert every public-health project into quantifiable modules with pre-set labor-hour quotas.Bonuses were calculated under"more work,more pay"and"increment incentive"rules,while appraisal covered two dimensions:(ⅰ)project-specific indicators(coverage,timeliness,completeness)and(ⅱ)outcome evaluation(health impact and user satisfaction).Performance pay was then approved and dis-tributed to staff responsible for project management.Results Analysis of the 2022-2024 implementation period showed clear gains:① Work-force mobilization:departments managing MCH projects grew from 17 to 22 and staff from 22 to 73;all core pro-ject indicators improved significantly.② Service expansion:valid service volume generated by jurisdiction-level MCH project ac-tivities rose by 62.31％.Conclusion The scientific,standardized and operable performance and evaluation system for maternity and child projects developed in this study can help effectively improve the management efficiency of maternity and child projects in the jurisdiction and promote the high-quality development of the hospital.

Objective To investigate the changes of macrophages and hemophagocytes in bone marrow smears of patients with multiple myeloma(MM)before and after chemotherapy and their correlation with clinical prognostic value.Methods A total of 300 MM patients treated in Liaocheng Second People's Hospital Affiliated to Shandong First Medical University from June 2018 to June 2023 were selected as the study objects.All patients received at least 3 courses of chemotherapy and were divided into the remission group(n=214)and the non-remission group(n=86)according to the clinical effect.Immunoglobulin(Ig)A,IgG,CD3+,CD4+,CD8+,interleukin(IL-2),IL-4,IL-6,IL-17,tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β,macrophages and hemophagocytes were detected in the two groups and compared between the two groups.COX regression was used to analyze the relationship between immunological indexes and non-remission of chemotherapy.The relationship between macrophages and hemophagocytes and non-remission of chemotherapy was analyzed by restricted cubic spline.The multiplicative interaction of macrophages and hemophagocytes on non-remission of chemotherapy was analyzed using an unconditioned Logistic regression model,and the additive interaction was analyzed using the interaction calculation table.Receiver operating characteristic(ROC)curve analysis of macrophages and hemophagocytes alone or in combination to determine the value of chemotherapy non-remission.Results The overall response rate(ORR)and non-response rate(NRR)of MM patients were 71.33%and 28.67%respectively.Compared with before treatment,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes were significantly decreased in both groups after treatment(tslow=9.252～61.177,tnot slow=4.057～35.797).CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly increased(tslow=9.706～33.940,tnot slow=4.227～16.167),and the differences were statistically significant(all P<0.05).After treatment,compared with the remission group,IgA,IgG,CD8+,IL-6,IL-17,TNF-α,TGF-β,macrophages and hemophagocytes in the non-remission group were significantly higher than those in remission group(t=3.362～30.028),CD3+,CD4+,CD4+/CD8+,IL-2 and IL-4 were significantly lower than those in remission group(t=3.736～13.998).and the differences were statistically significant(all P＜0.05).After adjusting the influence of other factors by COX regression,the trend test of macrophages and hemophagocytes was still statistically significant the trend test of macrophages and hemophagocytes was still statistically significant(P<0.05).Patients with≥5 macrophages/tablet and≥3 hemophagocytes/tablet had a significantly increased risk of non-remission from chemotherapy(P<0.05).There were additive(OR=6.157,95%CI:3.768～12.978)and multiplicative(OR=5.648,95%CI:1.035～17.492)interactions between macrophages and hemophagocytes in the non-remission of chemotherapy.Compared with the single judgment of macrophages and hemophagocytes,the combination of the two has the highest accuracy in determining chemotherapy non-remission(P＜0.05).Conclusion Macrophages and hemophagocytic cells in MM patients after chemotherapy are significantly lower than those before chemotherapy,with≥5 macrophages/tablet and≥3 hemocyte phages/tablet,indicating that the risk of non-remission in patients with chemotherapy increased significantly,and the combination of the two can accurately judge the clinical efficacy.

Objective Maternal-and-child health(MCH)hospitals simultaneously provide clinical care and manage community-based public-health projects for women and children.We aimed to design and test a performance-based salary and e-valuation system that recognizes this dual responsibility and incentivizes high-quality public-health work.Methods Aligned with the national tertiary-level MCH-hospital performance appraisal standards and local project realities,we applied four industrial-en-gineering techniques—empirical time-and-motion estimation,classification,analogy and work-study—to convert every public-health project into quantifiable modules with pre-set labor-hour quotas.Bonuses were calculated under"more work,more pay"and"increment incentive"rules,while appraisal covered two dimensions:(ⅰ)project-specific indicators(coverage,timeliness,completeness)and(ⅱ)outcome evaluation(health impact and user satisfaction).Performance pay was then approved and dis-tributed to staff responsible for project management.Results Analysis of the 2022-2024 implementation period showed clear gains:① Work-force mobilization:departments managing MCH projects grew from 17 to 22 and staff from 22 to 73;all core pro-ject indicators improved significantly.② Service expansion:valid service volume generated by jurisdiction-level MCH project ac-tivities rose by 62.31％.Conclusion The scientific,standardized and operable performance and evaluation system for maternity and child projects developed in this study can help effectively improve the management efficiency of maternity and child projects in the jurisdiction and promote the high-quality development of the hospital.

OBJECTIVE To establish a chromatography-mass spectrometry method for simultanenous detection of 3 genotoxic impurities in pantoprazole sodium. METHODS The chromatographic column was octadecylsilane bonded silica gel as filler (Kromasil 100-5, 4.6 mm×25 cm, 5 μm or equivalent column), acetonitrile-0.01 mol·L−1 ammonium acetate(35∶65) as mobile phase, flow rate 0.9 mL·min−1, column temperature 25 ℃; positiveion detection mode, scanning range: 150−450 Da, dryer temperature 350 ℃, dry gas flow rate 10 L·min−1, atomization gas pressure 50 psig, capillary voltage 4 000 V, fragmentation voltage 175 V, cone hole voltage 65 V. The time for entering the mass spectrometry was set to 0−3.5 minutes to waste, 3.5 minutes to retain the main peak-0.5 minutes to MS, and 0.5 minutes to end to waste. RESULTS The concentration of genotoxic impurity 1 had a good linear relationship with peak area between 9.04−27.13 ng·mL−1(r=0.998), the concentration of genotoxic impurity 2 had a good linear relationship with peak area between 8.92−26.75 ng·mL−1(r=0.999), and the concentration of intermediate II had a good linear relationship with peak area between 7.78−23.34 ng·mL−1(r=0.990); the quantitative limit of genotoxic impurity 1 was 9.0430 ng·mL−1, and the detection limit was 0.9043 ng·mL−1; the quantitative limit of genotoxic impurity 2 was 8.9174 ng·mL−1, and the detection limit was 2.9725 ng·mL−1; the quantitative limit of intermediate II was 7.7792 ng·mL−1, and the detection limit was 0.7779 ng·mL−1; the recovery rate of 3 genotoxic impurities ranges from 92.3%−107.0%, with an RSD of 2.0%−7.9%. No three impurities were detected in pantoprazole sodium. CONCLUSION This method can accurately and quantitatively determine three genotoxic impurities of pantoprazole sodium raw material: genotoxic impurity 1, genotoxic impurity 2, and intermediate II. The method has strong specificity, high sensitivity, simple and rapid experimental operation, and can be used for the determination of the above three genotoxic impurities in pantoprazole sodium.

Objective:To investigate the detection status and genotypes distribution characteristics of norovirus(NoV)in environmental sewage from three monitoring points in Fujian province, and to explore the significance of its application to NoV monitoring.Methods:Sewage samples were collected monthly at 5 sampling sites in representative monitoring cities, enriched and concentrated. Partial gene fragments of norovirus VP1 were amplified by reverse transcription-semi nested polymerase chain reaction (RT-snPCR), TA cloned and sequenced. Genotypes were identified based on the sequencing.Results:A total of 56 sewage samples were collected from July 2022 to June 2023. The detection rates of GⅠ and GⅡ were 89.29% (50/56) and 94.64% (53/56), respectively. A total of 7 NoV GⅠ genotypes and 13 GⅡgenotypes were identified. GⅠ.1, GⅠ.4, GⅡ.4 and GⅡ.17 were the dominant genotypes. NoV genotypes detected in different sampling sites were not exactly the same. The detection rate of NoV was low from August to November 2022, and the prevalence of the dominant genotypes was different in different seasons. GⅠ.1 and GⅡ.4 were highly prevalent from August to November 2022, but were replaced by GⅠ.4 and GⅡ.17 from December 2022 to June 2023, respectively. More NoV genotypes were detected in January-June 2023, comparing to the July-December 2022. The dominant genotype GII.17, has multiple clades and new variants have been discovered that are different from the 2014/2015 circulating strains.Conclusions:The detection rates of NoV in environmental sewage were very high, and genotypes were diverse. Environmental sewage surveillance could be an important complementary method for NoV cases surveillance.

Objective : To analyze the genome structure and genetic characteristics of IncpGRT1 plasmids from Pseud⁃ omonas , and elucidate its potential transmission risk . Methods : The genomic DNA of the clinical isolate 15420352 was extracted after purification and preservation of the strain , and then the whole genome was sequenced , and then the type of the plasmid was identified . Sequence annotation and comparison of the backbone region and the accessory modules were performed on all five same type sequenced plasmids , including one plasmid p420352 - strA in this study and four from GenBank . The plasmids were annotated by RAST , Plasmidfinder , Blast , ResFinder , and ISfinder. The ORFs of the plasmid were annotated and drug resistance genes were found . Results : All five plasmids were classified as new IncpGRT1 type plasmids . The IncpGRT1 backbone genes or gene loci were in all five plasmids , and they contained an auxiliary replicon besides the primary IncpGRT1 replicon . Five IncpGRT1 plasmids carried at least three different accessory modules , including the srp region , the msr region , and a Tn5053 family transposon . Three resistance genes strA , strB , and mer were obtained in these plasmids , which were involved in resistance to two categories of antibiotics and heavy metals . We also found that these plasmids carried at least one virulence gene msr and five key transporters srp , emrE , mod , phn , and lpt , which could improve the environmental adaptability of the strains . Conclusion The IncpGRT1 plasmids have become the important vector for the accumulation and spread of some drug resistance genes and virulence genes in Pseudomonas , and have improved the environmental adaptability of the strain.