OBJECTIVE To provide technical support for improving recognition rate of adverse drug events （ADEs） related to traditional Chinese medicine （TCM） formula granules and decoction pieces among inpatient patients. METHODS By referencing the global trigger tool （GTT） whitepaper， literature on adverse reactions to TCM， and expert review opinions， ADE trigger items for TCM formula granules and decoction pieces used in the inpatients were established. GTT was applied to analyze ADEs in inpatients who had used TCM formula granules and decoction pieces in our hospital from August 2013 to August 2023， utilizing the Chinese Hospital Pharmacovigilance System. The effectiveness of GTT and the characteristics of these ADEs were analyzed. RESULTS A total of forty-eight triggers were established， including thirty-two laboratory test indexes， thirteen clinical symptoms， and three antidotes. Among the 1 682 patients included， GTT identified 652 potential ADEs， 284 true positive ADEs，with a trigger rate of 38.76% and a positive predictive value of 43.56%. After review by the auditor， 278 cases of ADEs were finally confirmed， with an incidence rate of 16.53%， significantly higher than the number of spontaneously reported ADEs during the same period （0）. The 278 cases of ADEs were mostly grade 1 （223 cases）， mainly involving hepatobiliary system， gastrointestinal system， blood- lymphatic system， etc；a total of 219 types of TCMs are involved，and the top five suspected TCMs used at a frequency higher than 1% were Poria cocos， Codonopsis pilosula， Atractylodes macrocephala， fried Glycyrrhiza uralensis， and Scutellaria baicalensis. CONCLUSIONS The established GTT can improve the recognition rate of ADEs for hospitalized patients using traditional Chinese medicine formula granules and decoction pieces.

OBJECTIVE To investigate the effects of peiminine B （PEI） on Streptococcus pneumoniae （SP）-induced alveolar epithelial cell injury by regulating the Ras-related C3 botulinum toxin substrate 1 in nucleus accumbens （Rac1）/protein kinase B （Akt）/nuclear factor κB （NF-κB） signaling pathway. METHODS Human alveolar epithelial cells （HPAEpiC） were taken and randomly divided into the Control group， SP group （1×108 cfu/mL SP bacterial solution）， low-， medium-， and high-concentration PEI groups （1×108 cfu/mL SP bacterial solution+0.05， 0.10， 0.20 mmol/L PEI）， and high-concentration PEI+Akt activator group （P-H+SC79 group， 1×108 cfu/mL SP bacterial solution+0.20 mmol/L PEI+10 μmol/L SC79）. Except for the Control group， the other groups of cells were treated with SP bacterial solution and/or corresponding drug solution. After 24 h of treatment， the levels of inflammatory factors （interleukin-6， -18， -1β） in the supernatant solution， the contents of oxidative stress indexes [lactate dehydrogenase （LDH）， reactive oxygen species （ROS） and superoxide dismutase （SOD）]， apoptosis rate， as well as the expressions of proliferation/apoptosis-related proteins [cyclin-dependent kinase 1 （CDK1）， B cell lymphoma-2 related X protein （Bax）] and pathway-related proteins （Rac1， Akt， phosphorylated Akt， NF-κB and phosphorylated NF-κB） were detected in each group. RESULTS Compared with the Control group， the levels of inflammatory factors in supernatant solution， LDH and ROS contents， apoptosis rate， the protein expressions of Bax and Rac1 and the phosphorylation levels of Akt and NF-κB in the SP group were significantly increased or up-regulated， while SOD content and the protein expression of CDK1 were significantly decreased or down-regulated （P＜0.05）. Compared with the SP group， the above indexes in PEI groups were significantly improved in a concentration-dependent manner （P＜0.05）. SC79 could significantly reverse the improvement effect of the high concentration of PEI （P＜0.05）. CONCLUSIONS PEI can alleviate SP-induced inflammation and oxidative stress damage of alveolar epithelial cells and inhibit apoptosis， which may be achieved by inhibiting Rac1/Akt/NF-κB signaling pathway.

Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

ObjectiveTo investigate the effect of phytoestrogen biochanin A （BCA） on liver fibrosis induced by CCl₄ in female mice with bilateral oophorectomy （ovariectomized） and its mechanism. MethodsA total of 50 ovariectomized Kunming mice were selected and given intraperitoneal injection of CCl₄ to establish a model of liver fibrosis， and then according to body weight， they were randomly divided into model group， positive control group， and low-， middle-， and high-dose BCA groups， with 10 mice in each group. In addition， 10 female mice in the same litter were given resection of a small amount of adipose tissue near both ovaries to establish the sham-operation group. The mice in the positive control group were given estradiol 2 mg/kg by gavage， and those in the low-， middle-， and high-dose BCA groups were given BCA by gavage at a dose of 25， 50， and 100 mg/kg， respectively， once a day for 7 consecutive weeks； the mice in the sham-operation group and the model group were given an equal volume of 0.5% sodium carboxymethyl cellulose solution by gavage. The mice were anesthetized and sacrificed after administration to collect samples. Liver index and uterus index were measured； HE staining and Masson staining were used to observe liver histopathological changes； the biochemical analysis was used to measure the activity of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； ELISA was used to measure the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in liver tissue， and Western blot was used to measure the relative protein expression levels of collagen Ⅰ， transforming growth factor-beta 1 （TGF-β₁）， alpha-smooth muscle actin （α-SMA）， estrogen receptor beta （ERβ）， and p-NF-κBp65/NF-κBp65 in liver tissue. The t-test was used for comparison of continuous data between two groups； a one-way analysis of various was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups and further comparison between two groups. ResultsCompared with the sham-operated group， the model group had a significant increase in liver index and a significant reduction in uterus index， as well as significant increases in the activities of serum AST and ALT， the levels of IL-6 and TNF-α in liver tissue， and the protein expression levels of collagen Ⅰ， TGF-β₁， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in the expression of ERβ in liver tissue （P>0.05）， and the model group showed significant fibrosis lesions in the liver， such as hepatocyte edema， steatosis， and necrosis with inflammatory cell infiltration and hyperplasia， deposition， and staggered distribution of collagen fibers. Compared with the model group， the low-， middle-， and high-dose BCA groups had significant reductions in liver index， the activities of serum AST and ALT， the levels of IL-6 and TNF-α， and the protein expression levels of collagen Ⅰ， TGF-β₁， α-SMA， and p-NF-κBp65/NF-κBp65 in liver tissue （all P<0.05）， with no significant change in uterine index （P>0.05）， as well as a significant increase in the protein expression level of ERβ in liver tissue （P<0.05） and varying degrees of improvement in liver fibrosis lesions. ConclusionBCA can effectively improve CCL₄-induced liver fibrosis in ovariectomized female mice， possibly by upregulating ERβ to inhibit the NF-κB signaling pathway and then alleviating inflammatory response.

Mitochondria are the main site of energy metabolism in cardiomyocytes， and at the same time mediate apoptosis and immune response， so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure， it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs"， according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency， and qi deficiency leads to the weakness of the sweat pore opening and closing， or even the sweat pore closure， then resulting in qi deficiency and blood stasis， collaterals stagnation fail to flourish， and qi， blood， and body fluids can not infiltrate and nourish zang-fu organs， so that the heart fail to be nourished， and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore， using acridity to unblock the collaterals， and invigorating blood and draining water， with medicinal of boosting qi， invigorating blood， and draining water as treatment.

Objective To investigate the cell membrane-penetrating capacity of human cell-penetrating peptide hPP10 carrying human antioxidant protein Cu-Zn superoxide dismutase(Cu,Zn-SOD)and assess the antioxidant and anti-inflammatory activity of these fusion proteins.Methods The fusion protein hPP10-Cu,Zn-SOD was obtained by genetic engineering and identified by Western blotting.The membrane-penetrating ability of the fusion protein was evaluated by immunofluorescence assay,fluorescence colocalization assay and Western blotting,its SOD enzyme activity was detected using a commercial kit,and its effect on cell viability was assessed with MTT assay.In a HEK293 cell model of H2O2-induced oxidative stress,the effect of hPP10-Cu,Zn-SOD on cell apoptosis was analyzed with flow cytometry and RT-qPCR,and its antioxidant effect was assessed using reactive oxygen species(ROS)assay;its anti-inflammatory effect was evaluated in mouse model of TPA-induced ear inflammation by detecting expression of the inflammatory factors using RT-qPCR,Western blotting and immunohistochemistry.Results The fusion protein hPP10-Cu,Zn-SOD was successfully obtained.Immunofluorescence assay confirmed obvious membrane penetration of this fusion protein in HEK293 cells,localized both in the cell membrane and the cell nuclei after cell entry.hPP10-Cu,Zn-SOD at the concentration of 5 μmol/L exhibited strong antioxidant activity with minimal impact on cell viability at the concentration up to 10 μmol/L.The fusion protein obviously inhibited apoptosis and decreased intracellular ROS level in the oxidative stress cell model and significantly reduced mRNA and protein expression of the inflammatory factors in the mouse model of ear inflammation.Conclusion The fusion protein hPP10-Cu,Zn-SOD capable of penetrating the cell membrane possesses strong antioxidant and anti-inflammatory activities with only minimal cytotoxicity,demonstrating the value of hPP10 as an efficient drug delivery vector and the potential of hPP10-Cu,Zn-SOD in the development of skincare products

Objective To explore the relationship between collateral circulation and the prognosis of acute ischemic stroke(AIS)patients with successful recanalization after mechanical thrombectomy.Methods A total of 75 AIS patients who received mechanical thrombectomy at the First Affiliated Hospital of Xinxiang Medical University from September 2020 to May 2022 were selected as the research subjects.The clinical data of the patients were collected.According to the modified Rankin scale(mRS)score at 90 days after operation,the patients were divided into the good prognosis group(mRS score≤2)and the poor prognosis group(mRS score ≥3).Univariate and multivariate logistic regression were used to analyze the factors affecting the prognosis of AIS patients with successful recanalization after mechanical thrombectomy.There were three types of collateral circulation:symmetrical collateral circulation,malignant collateral circulation,and other collateral circulation.The National Institutes of Health Stroke Scale(NIHSS)score at admission,the NIHSS score at discharge and changes of the NIHSS score of patients with different collateral circulations were compared.Results Among the 75 patients,43 had a good prognosis,and 32 had a poor prognosis.The incidence of poor prognosis was 42.67％.Univariate analysis showed that history of diabetes,time from onset to puncture(OPT),collateral circulation and NIHSS score were the factors effecting the prognosis of AIS patients with successful recanalization after mechanical thrombectomy(P＜0.05).Age,sex,history of atrial fibrillation,history of hypertension,history of smoking,history of stroke,thrombolytic therapy and modified thrombolysis in cerebral infarction grade were not related to the prognosis of AIS patients with successful recanalization after mechanical thrombectomy(P＞0.05).Multivariate logistic regression analysis showed that symmetrical collateral circulation,malignant collateral circulation,history of diabetes and OPT were independent influencing factors for the prognosis of AIS patients with successful recanalization after mechanical thrombectomy(P＜0.05).There was no significant difference in the admission NIHSS score among the patients with different collateral circulations(P＞0.05).The discharge NIHSS score of patients with symmetrical collateral circulation was significantly lower than that of patients with malignant collateral circulation,and the change in the NIHSS score was more significant than that of patients with malignant collateral circulation(P＜0.05).There was no significant difference in the discharge NIHSS score and change in the NIHSS score between patients with symmetrical collateral circulation and patients with other collateral circulation(P＞0.05),and between patients with malignant collateral circulation and patients with other collateral circulation(P＞0.05).Conclusion Symmetrical collateral circulation,malignant collateral circulation are independent factor affecting the prognosis of AIS patients with successful recanalization after mechanical thrombectomy.Symmetrical collateral circulation may help improve the neurological function of patients after mechanical thrombectomy,and malignant collateral circulation may lead to deterioration of neurological function in patients undergoing mechanical thrombectomy.

OBJECTIVE To improve the diagnosis and treatment level of critically ill infectious diseases， standardize the clinical application of nanopore sequencing and promote the sound development of the technology. METHODS Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society and Expert Committee of Precision Medicine for Clinical Treatment of Guangdong Pharmaceutical Association initiated and organized multidisciplinary experts to discuss and determine the consensus writing outline by using the nominal group method， forming a preliminary consensus draft； expert consultation was performed by using Delphi method， and then experts’ opinions were analyzed and revised to form consensus. RESULTS & CONCLUSIONS Consensuses of Experts on the Application of Nanopore Sequencing Technology in the Detection of Pathogenic Microorganisms covers targeted sequencing， metagenomic sequencing and whole genome sequencing， and is standardized in terms of sample collection and storage， detection process， bioinformatics analysis and report interpretation； the recommendations are provided for the key issues.

Objective To compare the safety and efficacy of direct thrombectomy versus bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke under different collateral circulation statuses.Methods Totally 93 patients with acute anterior circulation ischemic stroke admitted to the First Affiliated Hospital of Xinxiang Medical University from September 2020 to March 2023 were selected as the research subjects.Patients were divided into direct throm-bectomy group(n=47)and bridging thrombectomy group(n=46)based on the type of thrombectomy.Patients in the direct thrombectomy group received direct intravascular thrombectomy,while patients in the bridging thrombectomy group received intravenous thrombolysis with alteplase combined with mechanical thrombectomy.According computed tomography angiography,the collateral circulation Tan classification was applied to divide the patients into good collateral circulation sub-group and poor collateral circulation sub-group.The modified thrombolysis in cerebral infarction grading(mTICI)was used to evaluate vessel recanalization.Head computed tomography plain scan was performed at 24-48 hours postoperatively to assess if there was hemorrhagic transformation,and modified Rankin Scale score was performed at 90 days postoperatively.Information such as imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,prognosis and spontaneous non-traumatic symptomatic intracerebral hemorrhage(SICH)were collected.Results The age,gender,baseline Alberta stroke program early computed tomography score,baseline national institutes of health stroke scale score,proportions of hypertension,diabetes and atrial fibrillation,baseline systolic pressure,creatinine,baseline blood glucose,platelet count,occlusion site,stroke etiologies and collateral circulation status of patients in the two groups were not statistically significantly different(P＞0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between the two groups(P＞0.05).The hemorrhagic transformation rate of patients in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P＜0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between patients with good collateral circulation and patients with poor collateral circulation in the two groups(P＞0.05).The hemorrhagic transformation rate of patients with good and poor collateral circulation in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P＜0.05).Conclusion Under different collateral circulation conditions,the safety and efficacy of direct thrombectomy and bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke are similar,but bridging thrombectomy is more likely to result in cerebral hemorrhage transformation compared with direct thrombectomy.

Objective To investigate the cell membrane-penetrating capacity of human cell-penetrating peptide hPP10 carrying human antioxidant protein Cu-Zn superoxide dismutase(Cu,Zn-SOD)and assess the antioxidant and anti-inflammatory activity of these fusion proteins.Methods The fusion protein hPP10-Cu,Zn-SOD was obtained by genetic engineering and identified by Western blotting.The membrane-penetrating ability of the fusion protein was evaluated by immunofluorescence assay,fluorescence colocalization assay and Western blotting,its SOD enzyme activity was detected using a commercial kit,and its effect on cell viability was assessed with MTT assay.In a HEK293 cell model of H2O2-induced oxidative stress,the effect of hPP10-Cu,Zn-SOD on cell apoptosis was analyzed with flow cytometry and RT-qPCR,and its antioxidant effect was assessed using reactive oxygen species(ROS)assay;its anti-inflammatory effect was evaluated in mouse model of TPA-induced ear inflammation by detecting expression of the inflammatory factors using RT-qPCR,Western blotting and immunohistochemistry.Results The fusion protein hPP10-Cu,Zn-SOD was successfully obtained.Immunofluorescence assay confirmed obvious membrane penetration of this fusion protein in HEK293 cells,localized both in the cell membrane and the cell nuclei after cell entry.hPP10-Cu,Zn-SOD at the concentration of 5 μmol/L exhibited strong antioxidant activity with minimal impact on cell viability at the concentration up to 10 μmol/L.The fusion protein obviously inhibited apoptosis and decreased intracellular ROS level in the oxidative stress cell model and significantly reduced mRNA and protein expression of the inflammatory factors in the mouse model of ear inflammation.Conclusion The fusion protein hPP10-Cu,Zn-SOD capable of penetrating the cell membrane possesses strong antioxidant and anti-inflammatory activities with only minimal cytotoxicity,demonstrating the value of hPP10 as an efficient drug delivery vector and the potential of hPP10-Cu,Zn-SOD in the development of skincare products