Objective:To investigate the effect of riboflavin on cerebral infarction volume and the possible mecha-nism of apoptotic factors with cerebral ischemic injury in mice.Methods:Eighteen C57BL/6J male mice were divided into the sham group,middle cerebral artery occlusion(MCAO)group and riboflavin intervention group(MCAO+RF)randomly.TTC staining was used to observe the infarction of the cerebral tissues;Quantitative real-time PCR(RT-qPCR)was used to detect the mRNA expression of tumor protein p53(p53),cytochrome C(CytC),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),cysteinyl aspartate specific proteinase-3(caspase-3),poly ADP-ribose poly-merase(PARP),cysteinyl aspartate specific proteinase-6(caspase-6)and apoptosis inducing factor(AIF)in different groups,to study the possible mechanism of riboflavin inhibiting neuronal apoptosis.The proteins expression of acetyl-p53(AC-p53),caspase-3 and PARP were analyzed by Western blot.Results:Compared with the MCAO group,the cerebral infarct volume of the MCAO+RF group was obviously reduced(P＜0.01);The relative expression of p53,CytC,caspase-3,PARP,caspase-6 and AIF were significantly lower in the MCAO+RF group(P＜0.05).Addition-ally,significant differences were observed in the proteins expression of AC-p53,caspase-3 and PARP between the MCAO group and MCAO+RF group.Conclusion:Riboflavin has a protective effect against cerebral ischemic injury,which is possibly realized by inhibiting neuronal apoptosis through multiple pathways.

Objective:This study aimed to investigate the regulatory role and mechanism of myosin heavy chain 9 (MYH9) in the invasion of Zika virus (ZIKV) into human glioma cells (U251).Methods:Utilizing CRISPR/Cas9 technology, MYH9-knockout U251 cells (U251-MYH9 KD) were constructed. Following ZIKV infection, the protein expression levels, RNA load, and viral titer of ZIKV were detected through western blot (WB), Real-time fluorescence quantitative polymerase chain reaction (qPCR), and plaque formation assays, respectively. The infection efficiency of ZIKV in U251 cells treated with the MYH9 inhibitor blebbistatin was assessed. The binding and internalization efficiency of ZIKV were measured in U251-MYH9 KD cells. The interaction between MYH9 and the ZIKV envelope protein (E) was studied using co-immunoprecipitation (Co-IP). The effects of soluble MYH9 recombinant protein and anti-human MYH9 antibodies on ZIKV infection were evaluated by qPCR and plaque formation assays. Results:It was found that knockout or inhibition of MYH9 significantly suppressed ZIKV infection in U251 cells. MYH9 knockout notably inhibited the binding and internalization of ZIKV in U251 cells. MYH9 interacted with the ZIKV E protein, and both MYH9 recombinant protein and anti-human MYH9 antibodies, by blocking the binding of ZIKV E protein to cell surface MYH9, inhibited ZIKV infection in U251 cells in a dose-dependent manner.Conclusions:MYH9 facilitates ZIKV invasion into U251 cells through interaction with the ZIKV E protein.

Objective: To investigate the association between overweight, obesity, central obesity and hypertension, so as to provide the basis for formulating targeted hypertension prevention and control strategies. Methods: Permanent residents aged ≥18 years were selected in Wenzhou City, Zhejiang Province from June 2023 to August 2024 by a multistage cluster random sampling method. Data on demographic information, lifestyle, height, weight, waist circumference (WC), blood pressure, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. The prevalence of hypertension was calculated and standardized using the data of the Sixth National Population Census in 2010. Body mass index (BMI) was calculated to determine overweight and obesity, while WC was used to identify central obesity. The association between overweight, obesity, central obesity and hypertension were analyzed using multivariable logistic regression models. Results: A total of 38 593 residents were surveyed, including 19 481 (50.48%) males and 19 112 (49.52%) females. The median age was 46.00 (interquartile range, 26.00) years. The rates of overweight, obesity, and central obesity were 32.74% (12 634 individuals), 10.27% (3 963 individuals), and 27.87% (10 755 individuals), respectively. There were 11 813 cases of hypertension, with a prevalence and standardized prevalence of 30.61% and 24.41%, respectively. Multivariable logistic regression analysis showed that after adjusting for demographic information, lifestyle, diabetes and dyslipidemia, the likelihood of hypertension in the overweight and obesity groups was 1.927 (95%CI: 1.815-2.045) times and 3.724 (95%CI: 3.404-4.073) times that of the normal BMI group, respectively. The likelihood of hypertension in the central obesity group was 2.346 (95%CI: 2.214-2.486) times that of the normal WC group. The likelihood of hypertension in the central obesity only, overweight only, overweight with central obesity, obesity only and obesity with central obesity groups was 1.586 (95%CI: 1.391-1.809), 1.704 (95%CI: 1.582-1.835), 2.433 (95%CI: 2.254-2.626), 1.768 (95%CI: 1.424-2.194), and 4.466 (95%CI: 4.053-4.921) times that of the normal BMI and WC group, respectively. Conclusions Overweight, obesity and central obesity were all associated with hypertension among adult residents. The highest likelihood of hypertension was observed among adult residents with both general obesity and central obesity.

Objective:To investigate the effect of riboflavin on cerebral infarction volume and the possible mecha-nism of apoptotic factors with cerebral ischemic injury in mice.Methods:Eighteen C57BL/6J male mice were divided into the sham group,middle cerebral artery occlusion(MCAO)group and riboflavin intervention group(MCAO+RF)randomly.TTC staining was used to observe the infarction of the cerebral tissues;Quantitative real-time PCR(RT-qPCR)was used to detect the mRNA expression of tumor protein p53(p53),cytochrome C(CytC),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X(Bax),cysteinyl aspartate specific proteinase-3(caspase-3),poly ADP-ribose poly-merase(PARP),cysteinyl aspartate specific proteinase-6(caspase-6)and apoptosis inducing factor(AIF)in different groups,to study the possible mechanism of riboflavin inhibiting neuronal apoptosis.The proteins expression of acetyl-p53(AC-p53),caspase-3 and PARP were analyzed by Western blot.Results:Compared with the MCAO group,the cerebral infarct volume of the MCAO+RF group was obviously reduced(P＜0.01);The relative expression of p53,CytC,caspase-3,PARP,caspase-6 and AIF were significantly lower in the MCAO+RF group(P＜0.05).Addition-ally,significant differences were observed in the proteins expression of AC-p53,caspase-3 and PARP between the MCAO group and MCAO+RF group.Conclusion:Riboflavin has a protective effect against cerebral ischemic injury,which is possibly realized by inhibiting neuronal apoptosis through multiple pathways.

Objective:This study aimed to investigate the regulatory role and mechanism of myosin heavy chain 9 (MYH9) in the invasion of Zika virus (ZIKV) into human glioma cells (U251).Methods:Utilizing CRISPR/Cas9 technology, MYH9-knockout U251 cells (U251-MYH9 KD) were constructed. Following ZIKV infection, the protein expression levels, RNA load, and viral titer of ZIKV were detected through western blot (WB), Real-time fluorescence quantitative polymerase chain reaction (qPCR), and plaque formation assays, respectively. The infection efficiency of ZIKV in U251 cells treated with the MYH9 inhibitor blebbistatin was assessed. The binding and internalization efficiency of ZIKV were measured in U251-MYH9 KD cells. The interaction between MYH9 and the ZIKV envelope protein (E) was studied using co-immunoprecipitation (Co-IP). The effects of soluble MYH9 recombinant protein and anti-human MYH9 antibodies on ZIKV infection were evaluated by qPCR and plaque formation assays. Results:It was found that knockout or inhibition of MYH9 significantly suppressed ZIKV infection in U251 cells. MYH9 knockout notably inhibited the binding and internalization of ZIKV in U251 cells. MYH9 interacted with the ZIKV E protein, and both MYH9 recombinant protein and anti-human MYH9 antibodies, by blocking the binding of ZIKV E protein to cell surface MYH9, inhibited ZIKV infection in U251 cells in a dose-dependent manner.Conclusions:MYH9 facilitates ZIKV invasion into U251 cells through interaction with the ZIKV E protein.

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

Objective To investigate the surgical method and clinical outcome using the free anterolateral thigh flap with the medial gastrocnemius artery as the recipient artery for the repair of complex wounds in the lower leg. Methods A retrospective analysis was conducted on the clinical data of 11 patients with complex wounds in the lower leg admitted to Suzhou Ruihua Orthopedic Hospital from October 2020 to September 2022. All patients had extensive skin and subcutaneous soft tissue defects in the lower leg and received free anterolateral thigh flap repair with the medial gastrocnemius artery as the recipient artery. The skin of donor site was directly sutured. Results All 11 free skin flap survived in 11 patients, and both the donor and recipient sites healed in stage I. All patients were followed up after discharge, with a follow-up time of 12 to 35 months. The follow-up results at 12 months postoperatively showed good wound healing, good flap appearance and elasticity, restoration of normal knee and ankle joint function, and independent living ability. The donor site wounds healed well without significant scar hyperplasia. At the last follow-up, the flap sensory function was graded as S₃ in 2 patients and S₂ in 9 patients. The functional score of the affected limb was excellent in 5 patients and good in 6 patients, with an excellent and good rate of 100%. Conclusion The medial gastrocnemius artery has a suitable vessel caliber for anastomosis and a constant location. The use of the free anterolateral thigh flap with this artery as the recipient artery for the repair of severe wounds in the lower leg can effectively cover soft tissue defects and avoid injuring the residual main vessels in the lower leg, resulting in satisfactory outcomes.

Objective:To mine the risk signals of adverse events of limaprost and provide reference for safe use of the drug.Methods:US FDA Public Data Open Project (OpenFDA) platform was searched, and the adverse event (AE) reports on limaprost from January 1, 2004 to October 1, 2023 were collected. AEs were classified and standardized according to the system organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.1. The reporting odds ratio (ROR) method was used to mine the risk signal of limaprost. An AE with reports ≥3, ROR ≥2 and the lower limit of the 95% confidence interval ( CI)>1 was defined as a risk signal, which was analyzed descriptively. Results:A total of 1 618 AE reports with limaprost as the primary suspect drug were collected, 69 risk signals were identified, involving 17 SOCs. Of the 69 PTs, 10 were recorded in the drug instructions including hepatic function abnormal, red blood cell count decreased, drug eruption, blood pressure decreased, liver disorder, platelet count decreased, anaemia, haemoglobin decreased, pyrexia, and decreased appetite. The other 59 risk signals were not recorded in the drug instructions. The top 10 PTs in signal intensity were scleroderma, tumour haemorrhage, brain natriuretic peptide increased, inappropriate antidiuretic hormone secretion, colitis microscopic, large intestine perforation, cardiac failure acute, depressive symptom, cardiac failure chronic, pulmonary alveolar haemorrhage. The risk signals with more than 10 reports were inappropriate antidiuretic hormone secretion, interstitial lung disease, renal impairment, cardiac failure, pneumonia, fall, etc.Conclusion:In addition to the AEs recorded in the instructions, limaprost may also cause serious adverse reactions such as tumour haemorrhage, brain natriuretic peptide increased, and inappropriate antidiuretic hormone secretion, which are not recorded in the instructions and have a poor prognosis.

Objective:To mine the risk signals of adverse events of limaprost and provide reference for safe use of the drug.Methods:US FDA Public Data Open Project (OpenFDA) platform was searched, and the adverse event (AE) reports on limaprost from January 1, 2004 to October 1, 2023 were collected. AEs were classified and standardized according to the system organ class (SOC) and preferred terms (PT) of Medical Dictionary for Regulatory Activities version 25.1. The reporting odds ratio (ROR) method was used to mine the risk signal of limaprost. An AE with reports ≥3, ROR ≥2 and the lower limit of the 95% confidence interval ( CI)>1 was defined as a risk signal, which was analyzed descriptively. Results:A total of 1 618 AE reports with limaprost as the primary suspect drug were collected, 69 risk signals were identified, involving 17 SOCs. Of the 69 PTs, 10 were recorded in the drug instructions including hepatic function abnormal, red blood cell count decreased, drug eruption, blood pressure decreased, liver disorder, platelet count decreased, anaemia, haemoglobin decreased, pyrexia, and decreased appetite. The other 59 risk signals were not recorded in the drug instructions. The top 10 PTs in signal intensity were scleroderma, tumour haemorrhage, brain natriuretic peptide increased, inappropriate antidiuretic hormone secretion, colitis microscopic, large intestine perforation, cardiac failure acute, depressive symptom, cardiac failure chronic, pulmonary alveolar haemorrhage. The risk signals with more than 10 reports were inappropriate antidiuretic hormone secretion, interstitial lung disease, renal impairment, cardiac failure, pneumonia, fall, etc.Conclusion:In addition to the AEs recorded in the instructions, limaprost may also cause serious adverse reactions such as tumour haemorrhage, brain natriuretic peptide increased, and inappropriate antidiuretic hormone secretion, which are not recorded in the instructions and have a poor prognosis.

OBJECTIVE To conduct data mining on drugs causing liver failure in underage populations based on the FDA Adverse Event Reporting System （FAERS） database， so as to provide reference for clinical use of related drugs. METHODS The data on reported adverse drug event （ADE） of liver failure in this population （under 18 years old） from the first quarter of 2013 to the third quarter of 2022 were retrieved from the FAERS database for mining and analysis； they were divided into infants（≤1 year old）， young children（＞1-＜6 years old）， children（6-＜12 years old） and adolescents（12-＜18 years old） according to the age. The reporting odds ratio （ROR）， proportional reporting ratio and Bayesian confidence propagation neural network of the proportional imbalance method were used to screen ADE signals. RESULTS A total of 1 051 ADE reports of liver failure were collected from the underage population involving 60 drugs. The highest incidence was found in adolescents （410 cases， 39.01%）， followed by young children （297 cases， 28.26%）. The instructions of 14 drugs did not mention hepatobiliary system injury and liver failure risk， including 31 cases of levetiracetam （2.95%），18 cases of metronidazole （1.71%）， 16 cases of each of topiramate and methylprednisolone （1.52% each）， 12 cases of dexamethasone （1.14%）， 11 cases of tisagenlecleucel （1.05%）， 10 cases of each of ferrous sulfate， metformin and busulfan （0.95% each）， 9 cases of propofol （0.86%）， 8 cases of onasemnogene abeparvovec （0.76%）， 5 cases of each of diphenhydramine and omeprazole （0.48% each）， 4 cases of sebeliesterase α （0.38%）， totaling 165 cases， accounting for 15.70% of the total reported cases. Metformin was contrary to the known liver safety， and E-mail：libingchemical@163.com metronidazole and levetiracetam were new risk signals， which caused more serious clinical outcomes. CONCLUSIONS Fourteen new pharmacovigilance signals which cause liver failure in the underage population are found in this study； the liver function of patients should be closely monitored when using these drugs. Among those drugs， metformin neither undergoes liver metabolism nor has been reported in the relevant literature， and the liver-related ADE caused by metformin deserves further attention. The clinical outcomes caused by metronidazole and levetiracetam are relatively serious and need to be given sufficient attention.