The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

ObjectiveThis study aimed to evaluate the clinical effectiveness and safety of Guben Kechuan Granules （固本咳喘颗粒） in treating chronic bronchitis （CB） with lung qi weakness pattern. MethodsA multicenter， randomized controlled trial was conducted， and 180 patients with CB of lung qi weakness pattern were randomly divided into 120 cases in the treatment group and 60 cases in the control group according to a 2∶1 ratio. The control group received health education for 24 weeks， while conventional symptomatic treatment was given when acute exacerbation of CB occurred. Treatment group was treated with the oral administration of Guben Kechuan Granules， 2 g each time， 3 times a day， for a total of 24 weeks on the basis of treatment of the control group. Both groups were followed up for 24 weeks after 24 weeks of treatment. Primary effectiveness indicators included the number of CB acute exacerbations occurence during the treatment and follow-up period， and the total number of CB acute exacerbations from the start of treatment to the end of follow-up. Secondary effectiveness indicators included the details of CB acute exacerbations， i.e.， time to first acute exacerbation， time between acute exacerbations， duration of each time of acute exacerbation， and acute exacerbation symptom severity scores， and lung function indices. The scores of cough， sputum， and wheeze and total symptom scores were compared prior to treatment， at 4， 8， 12， 16， 20， and 24 weeks of treatment， and at 24 weeks of follow-up. The occurrence of adverse events during the study period was recorded and safety indices including blood routine， liver function， kidney function， and urine routine were tested. ResultsA total of 179 participants completed the trial including 119 in the treatment group and 60 in the control group. Compared to pre-treatment scores within the group， the treatment group showed reductions in cough， sputum， and wheeze scores， and total symptom scores at weeks 4， 8， 12， 16， 20， and 24 of treatment， as well as at 24 weeks of follow-up； in the control group， cough scores decreased at weeks 16， 20， and 24， sputum and wheeze scores decreased at week 24 of treatment and at 24 weeks of follow-up， and total symptom scores decreased at weeks 20， 24 of treatment， and at 24 weeks of follow-up （P＜0.05）. Compared with the control group， the treatment group showed reductions in the number of CB acute exacerbations occurence during the treatment and follow-up period， and the total number of CB acute exacerbations from the start of treatment to the end of follow-up， the duration of acute exacerbations， the acute exacerbation symptom severity scores， and the scores for cough， sputum， wheeze， and total symptoms at weeks 8， 12， 16， 20， 24 of treatment， and at 24 weeks of follow-up； while the time to the first acute exacerbation of CB was significantly prolonged in the treatment group （P＜0.05 or P＜0.01）. There were no statistically significant differences in lung function indicators between groups before treatment and at 24 weeks after treatment （P＞0.05）. Safety indicators showed no significant abnormalities before or after treatment in either group， and the incidence of adverse events during the treatment period showed no significant differences between the groups （P＞0.05）. ConclusionGuben Kechuan Granules can reduce the risk of acute exacerbations in CB patients with lung qi weakness pattern， improve clinical symptoms such as cough， sputum， and wheeze， and show good safety.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Purpose To explore the expression of SHIP2 in esophageal squamous cell carcinoma and its effect on the malignant biological behavior of ESCC cells.Methods The UALCAN database was used to analyze the expression of SHIP2 in esophageal cancer.qRT-PCR and immunohistochemistry SP method were used to measure the expression of SHIP2 in tumor tissues of ESCC patients.SHIP2 mRNA and protein were examined by qRT-PCR and Western blot in human normal esophageal epithelial cells(HEEC)and ESCC cells(KYSE150 and EC109).KYSE150 and EC109 were divided into the NC group and the si-SHIP2 group respectively.Cell proliferation,migration,and invasion were observed by CCK-8 assay,EdU assay,scratch assay,and Transwell assay.The expression of epithelial-mesenchymal transition-related proteins(E-cadherin,N-cadherin,and vimentin)was detected by Western blot.Results The UAL-CAN database showed that SHIP2 expression was higher in esophageal cancer than in normal tissues(P＜0.05).SHIP2 had higher mRNA(2.19±3.20)expression and staining scores(5.33±3.83)in ESCC tumor tissues than in paracarcinoma tissues(1.00±0.80;0.87±1.07,all P＜0.05).SHIP2 had higher mRNA(KYSE150,EC109:1.91±0.22,3.73±1.06)and protein(KYSE150,EC109:0.93±0.12,1.05±0.13)expression in ESCC cells than in HEEC(1.06±0.40;0.31±0.04,all P＜0.05).Cell function experiments showed that compared with the NC group(CCK-8 assay:KYSE150,EC109:2.44±0.12,3.56±0.07;EdU assay:KYSE150,EC109:44.46±4.74,38.82±3.79;scratch assay:KYSE150,EC109:0.85±0.07,0.70±0.06;Transwell migration assay:KYSE150,EC109:130.30±9.53,39.25±3.30;Transwell invasion assay:KYSE150,EC109:121.00±9.54、88.67±6.66);cell proliferation(CCK-8 assay:KYSE150,EC109:1.56±0.03,2.85±0.02,EdU assay:KYSE150,EC109:19.34±6.24,17.39±1.14);migration(scratch assay:KYSE150,EC109:0.51±0.09,0.36±0.02;Transwell migration assay:KYSE150,EC109:71.50±12.07,20.75±2.99),and invasion(Transwell in-vasion assay:KYSE150,EC109:73.33±4.04,12.67±2.31)ability in the si-SHIP2 group was significantly re-duced(all P＜0.05).Western blot results showed that compared with the NC group(0.48±0.21,0.42±0.24;1.00±0.04,1.17±0.18;1.34±0.10,1.00±0.13),the expression of E-cadherin protein(1.10±0.22,1.02±0.20)in the si-SHIP2 group was increased(P＜0.05),while the expression of N-cadherin protein(0.59±0.20,0.84±0.08)and vimentin protein(0.41±0.06,0.338±0.19)was decreased(P＜0.05).Conclusion SHIP2 is overexpressed in ESCC,and the down-regulation of SHIP2 can inhibit the proliferation,migration,and invasion of ES-CC cells.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Purpose To explore the expression of SHIP2 in esophageal squamous cell carcinoma and its effect on the malignant biological behavior of ESCC cells.Methods The UALCAN database was used to analyze the expression of SHIP2 in esophageal cancer.qRT-PCR and immunohistochemistry SP method were used to measure the expression of SHIP2 in tumor tissues of ESCC patients.SHIP2 mRNA and protein were examined by qRT-PCR and Western blot in human normal esophageal epithelial cells(HEEC)and ESCC cells(KYSE150 and EC109).KYSE150 and EC109 were divided into the NC group and the si-SHIP2 group respectively.Cell proliferation,migration,and invasion were observed by CCK-8 assay,EdU assay,scratch assay,and Transwell assay.The expression of epithelial-mesenchymal transition-related proteins(E-cadherin,N-cadherin,and vimentin)was detected by Western blot.Results The UAL-CAN database showed that SHIP2 expression was higher in esophageal cancer than in normal tissues(P＜0.05).SHIP2 had higher mRNA(2.19±3.20)expression and staining scores(5.33±3.83)in ESCC tumor tissues than in paracarcinoma tissues(1.00±0.80;0.87±1.07,all P＜0.05).SHIP2 had higher mRNA(KYSE150,EC109:1.91±0.22,3.73±1.06)and protein(KYSE150,EC109:0.93±0.12,1.05±0.13)expression in ESCC cells than in HEEC(1.06±0.40;0.31±0.04,all P＜0.05).Cell function experiments showed that compared with the NC group(CCK-8 assay:KYSE150,EC109:2.44±0.12,3.56±0.07;EdU assay:KYSE150,EC109:44.46±4.74,38.82±3.79;scratch assay:KYSE150,EC109:0.85±0.07,0.70±0.06;Transwell migration assay:KYSE150,EC109:130.30±9.53,39.25±3.30;Transwell invasion assay:KYSE150,EC109:121.00±9.54、88.67±6.66);cell proliferation(CCK-8 assay:KYSE150,EC109:1.56±0.03,2.85±0.02,EdU assay:KYSE150,EC109:19.34±6.24,17.39±1.14);migration(scratch assay:KYSE150,EC109:0.51±0.09,0.36±0.02;Transwell migration assay:KYSE150,EC109:71.50±12.07,20.75±2.99),and invasion(Transwell in-vasion assay:KYSE150,EC109:73.33±4.04,12.67±2.31)ability in the si-SHIP2 group was significantly re-duced(all P＜0.05).Western blot results showed that compared with the NC group(0.48±0.21,0.42±0.24;1.00±0.04,1.17±0.18;1.34±0.10,1.00±0.13),the expression of E-cadherin protein(1.10±0.22,1.02±0.20)in the si-SHIP2 group was increased(P＜0.05),while the expression of N-cadherin protein(0.59±0.20,0.84±0.08)and vimentin protein(0.41±0.06,0.338±0.19)was decreased(P＜0.05).Conclusion SHIP2 is overexpressed in ESCC,and the down-regulation of SHIP2 can inhibit the proliferation,migration,and invasion of ES-CC cells.

Objective To investigate the family aggregation of human hookworm infections in Sichuan Province and to identify its influencing factors, so as to provide insights into management of hookworm infections. Methods Three to four counties (districts) were sampled from basins, hilly regions and mountainous regions around the basins in Sichuan Province from 2017 to 2022 as fixed survey sites, and 17 to 30 counties (districts) were selected as mobile survey sites. At least 1 000 permanent residents at ages of 3 years and older were sampled from each survey site, and hookworm eggs were detected in human stool samples using the Kato-Katz technique. Subjects with 2 and more family members and at least 2 individuals diagnosed with hookworm infections in the county (district) where they lived were selected, and the familial aggregation of hookworm infections was analyzed using the test of goodness of fit for binomial distribution. In addition, the knowledge and practice of hookworm disease control were investigated among residents in Hejiang County and Wutongqiao District, Leshan City, Sichuan Province in 2021 and 2022, and the difference in the knowledge and practice of hookworm disease control was compared between members with and without familial aggregation of hookworm infections. Results A total of 66 812 residents from 25 196 households were sampled from main endemic areas of hookworm diseases in Sichuan Province from 2017 to 2022 for detection of hookworm infections, and 4 403 infections were identified (6.59% prevalence). The distribution of human hookworm infections in Sichuan Province did not fit the binomial distribution, and showed family aggregations (χ² = 2 116.759, P < 0.001). Family aggregation of human hookworm infections was found in endemic areas with 1% and higher prevalence of human hookworm infections (χ² = 136.006 to 428.738, all P values < 0.001), and family aggregation of human hookworm infections was identified in different years (χ² = 87.615 to 471.838, all P values < 0.001) and in different terrains of endemic areas (χ² = 8.423 to 1 144.176, all P values < 0.001). The members with hookworm infections had median eggs per gram of 180 (interquartile range, 780) in aggregated families and 72 (102) in non-aggregated families (Z = −2.686, P < 0.05). The proportion of members in families with aggregation of hookworm infections who knew the preventive measures of hookworm disease was significantly lower than in non-aggregated families (24.49% vs. 51.72%; χ² = 10.262, P < 0.05), and the proportion of members in families with aggregation of hookworm infections who often worked barefoot on the ground was significantly higher than in non-aggregated families (30.61% vs. 13.25%; χ² = 6.289, P < 0.05). Conclusions There is a familial aggregation of human hookworm infections in Sichuan Province, and awareness of preventive measures for hookworm disease and frequent working barefoot on the ground are associated with familial aggregation of hookworm infections.

Objective In this study,we attempted to investigate whether Electroacupuncture(EA)could promote the autophagy function in macrophages of inflammatory skin tissues by activating CB2 receptor,thus relieving inflammatory pain induced by CFA in mice,and whether activation of CB2 receptor in NR8383 macrophages cell line can simulate the effect of EA on the autophagy function and mitochondrial damage.Methods Inflammatory pain model was induced by CFA injection into the planta the hind paw of wildtype and CB2 knockout mice.EA or sham EA was applied on the left Huantiao(GB30)and Yanglingquan(GB34)sites.Thermal hyperalgesia was determined with the Hargreaves test.Mechanical sensitivity was assessed with von Frey filaments.NR8383 microphage cell line was used to study the effect of CB2 activation on macrophage function induced by CFA.The expression level of autophagy protein LC3 and p62 in wildtype and CB2 knockout mice skin tissue and NR8383 cell line were determined by Western blot.And flow cytometry analysis was applied to detect damaged mitochondria and mitochondrial superoxide.Results CFA significantly reduced the thermal and mechanical pain threshold in both wildtype and CB2 knockout mice,comparing with the vehicle control groups(P<0.01).EA significantly inhibited thermal and mechanical hyperpathia induced by CFA in wildtype mice(P<0.05),but had no effect on CB2 knockout mice with CFA(P>0.05).CFA significantly increased the expression of p62 protein and decreased LC3-II/I ratio,which was inversed by EA in wildtype mice but wasn't affected by EA in CB2 knockout mice.CFA increased the expression of p62 protein and decreased LC3-II/I ratio in NR8383 cell line,which were inversed by CB2 agonist AM1241.CFA increased mitochondria damage,which were then attenuated by CB2 agonist AM1241.Conclusion The analgesic effect of EA on inflammatory pain induced by CFA was mediated by activation of CB2 receptor,which promoted the autophagy function and the clearance of damaged mitochondria in macrophage.

Inflammatory caspase-11 senses and is activated by intracellular lipopolysaccharide (LPS) leading to pyroptosis that has critical role in defensing against bacterial infection, whereas its excess activation under pathogenic circumstances may cause various inflammatory diseases. However, there are few known drugs that can control caspase-11 activation. We report here that scutellarin, a flavonoid from Erigeron breviscapus, acted as an inhibitor for caspase-11 activation in macrophages. Scutellarin dose-dependently inhibited intracellular LPS-induced release of caspase-11p26 (indicative of caspase-11 activation) and generation of N-terminal fragment of gasdermin D (GSDMD-NT), leading to reduced pyroptosis. It also suppressed the activation of non-canonical nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as evidenced by reduced apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and decreased interleukin-1 beta (IL-1β) and caspase-1p10 secretion, whereas the NLRP3-specific inhibitor MCC950 only inhibited IL-1β and caspase-1p10 release and ASC speck formation but not pyroptosis. Scutellarin also suppressed LPS-induced caspase-11 activation and pyroptosis in RAW 264.7 cells lacking ASC expression. Moreover, scutellarin treatment increased Ser/Thr phosphorylation of caspase-11 at protein kinase A (PKA)-specific sites, and its inhibitory action on caspase-11 activation was largely abrogated by PKA inhibitor H89 or by adenylyl cyclase inhibitor MDL12330A. Collectively, our data indicate that scutellarin inhibited caspase-11 activation and pyroptosis in macrophages at least partly via regulating the PKA signaling pathway.

Objective To cxplore the optimal levels of serum calcium,phosphorus and intact parathyroid hormone (iPTH) in peritoneal dialysis (PD) patients.Methods This study is a single center,retrospective cohort study.The associations between serum calcium,phosphorus and iPTH and all-cause mortality in 217 PD patients were analyzed.All patients started PD between January 1,2008 and April 30,2016 were enrolled and followed up to December 31,2016.At baseline and every 3 months,biochemical and therapeutic information was collected.Cox proportional hazard regression models and cubic splines analysis were employed to assess the lowest mortality risk ranges in serum markers of bone metabolism.Results There was no significantly difference between patients within target ranges based on KDOQI or KDIGO guideline and those outside the target ranges by Kaplan-Meier survival analysis.The lowest mortality risk ranges were 2.17-2.40 mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH by using Cox models and cubic splines analysis.Moreover,cumulate survival had significant difference between patients within the descriptive ranges and those out of the descriptive ranges at time-averaged values but not at baseline values.Conclusions The optimal time-averaged ranges of PD patients are 2.17-2.40mmol/L for serum calcium,1.20-1.67 mmol/L for serum phosphorus and 180-350 ng/L for serum iPTH.These ranges need further validation by large population studies to further conform.