Objective To mine adverse drug event(ADE)signals of doxycycline using the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,and provide scientific evidence for clinical medication safety.Methods The data from the FAERS database between the first quarter of 2004 and the first quarter of 2024 were extracted.After data cleaning and standardization,ADE reports with doxycycline as the main suspected drug were screened.The system organ class(SOC)of ADE was performed using MedDRA,and the reporting odds ratio method and Medicines and Healthcare products Regulatory Agency method were used to mine ADE signals.The information component method was also used to evaluate signal strength.Results A total of 43 126 ADE reports with doxycycline as the primary suspected drug were collected,involving 14 642 patients,with a higher proportion of female patients(57.32％).There were 555 related ADE signals involving 26 SOC,with the top 5 SOC being gastrointestinal disorders,skin and subcutaneous tissue disorders,injuries,poisonings,and procedural complications,psychiatric disorders,and infections and infestations.The top 5 ADE signals with the highest signal intensity were Hatch reaction,sclerosing cholangitis,esophageal ulcer,gastrointestinal mucosal necrosis,and gastrointestinal injury.Among the ADE signals with the strongest signal strength not listed in the package insert,the top five were sclerosing cholangitis,nephrogenic diabetes insipidus,minimal change glomerular nephritis,diabetes insipidus and Sixth cranial nerve paralysis.Conclusion In clinical practice,particular attention should be paid to the frequent ADEs caused by doxycycline,as well as those not yet documented in the package insert,which involve multiple SOC such as renal and urinary disorders,hepatobiliary diseases,blood and lymphatic system disorders,and endocrine disorders.Therefore,clinical pharmacists should play a key role in assisting clinicians to develop and implement prevention plans for ADEs,thereby improving the safety of doxycycline in clinical use.

Objective To investigate the effects of Shenling Baizhu San on hepatic lipid metabolism in mice with metabolic associated fatty liver disease(MAFLD)based on the KLF16/PPAR-α signaling pathway.Methods C57 BL/6 mice were randomly divided into normal group,model group and Shenling Baizhu San low-,medium-and high-dose groups(2.685,5.369,10.738 g·kg-1·d-1),with seven mice in each group.Except for the normal group,the mice in the other groups were given high-fat diet for 12 weeks to replicate the MAFLD model.After the modeling,intragastric administration was started once a day for five weeks.The body mass and liver coefficient of mice were measured.HE and oil red O staining were used to observe the pathological changes of liver tissue in mice.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were detected.The mRNA expression levels of PPAR-α,KLF16,FAS and SREBP-1c in liver tissue were detected by RT-qPCR.Results Compared with the normal group,the body mass,liver mass and liver coefficient of mice in the model group were significantly increased(P＜0.05,P＜0.01).The levels of serum TG,TC,ALT and AST were significantly increased(P＜0.001).There were a large number of vacuoles in the cytoplasm of the liver tissue,and a large number of red-stained lipid droplets appeared in the cytoplasm.The NAS pathological score and oil red O staining IOD value were significantly increased(P＜0.05,P＜0.001).The mRNA expressions of PPAR-α and KLF16 in liver tissue were significantly down-regulated(P＜0.01,P＜0.001),and the mRNA expressions of FAS and SREBP-1c was significantly up-regulated(P＜0.05,P＜0.001).Compared with the model group,the body mass,liver mass and liver coefficient of mice in the high-dose group of Shenling Baizhu San were significantly decreased(P＜0.05).The levels of serum TG,TC and ALT in the low-,medium-and high-dose groups of Shenling Baizhu San were significantly decreased(P＜0.05,P＜0.01,P＜0.001).The serum AST level of mice in the medium-and high-dose groups of Shenling Baizhu San was significantly decreased(P＜0.01,P＜0.001).The pathological changes of liver tissue in each administration group were significantly improved,and the orange-red lipid droplets in the cytoplasm of hepatocytes were significantly reduced.The NAS pathological score and oil red O staining IOD value of the high-dose group of Shenling Baizhu San were significantly reduced(P＜0.05,P＜0.01);the mRNA expressions of PPAR-α and KLF16 in liver tissue of mice in Shenling Baizhu San low-,medium-and high-dose groups were significantly up-regulated(P＜0.05,P＜0.01,P＜0.001),and the mRNA expressions of FAS and SREBP-1c were significantly down-regulated(P＜0.05,P＜0.01,P＜0.001).Conclusion Shenling Baizhu San can significantly improve hepatic lipid metabolism in MAFLD mice,and its mechanism may be related to transcriptional regulation of nuclear receptor KLF16/PPAR-α signaling pathway.

BACKGROUND:Deferoxamine mesylate is a potential anti-osteoporosis drug with iron chelation,vascular regeneration,and antioxidant effects.Recent studies have shown that the application of deferoxamine mesylate can be extended to the field of tissue regeneration engineering. OBJECTIVE:To investigate whether deferoxamine mesylate can promote the repair effect of iron overload osteoporotic rats after bone grafting for mandibular bone defects by simulating the state of iron accumulation in patients with postmenopausal osteoporosis with high iron intervention in osteoporotic rats. METHODS:An iron accumulation ovariectomized osteoporosis model was firstly constructed.The model group underwent bilateral ovariectomy,and the intraperitoneal injection of ferric ammonium citrate(90 mg/kg,twice a week,for 11 weeks)was started in the 2nd week,while the sham-operated group had some fat around the ovaries removed and was given an equal amount of saline for 11 weeks.After the successful modeling,the experimental rats were divided into sham-operated group(n=6),high iron ovariectomtized group(n=6)and high iron ovariectomized deferoxamine mesylate treatment group(deferoxamine mesylate group,n=6).Bone defects of 5 mm in diameter were established in the rat's bilateral mandibles and implanted with Bio-Oss bone powder.Intraperitoneal injection of deferoxamine mesylate(100 mg/kg,3 times a week)was started on postoperative day 4 in the deferoxamine mesylate group,and equal volume of saline was given in the sham-operated and high iron ovariectomized groups.The bone samples of the mandible,liver and blood were taken at 2 and 12 weeks after bone grafting for Prussian blue staining of the jaw and liver and ELISA detection of serum ferritin to detect iron levels in various body tissues;hematoxylin-eosin staining and Masson staining were performed to observe inflammatory cell infiltration and early osteogenesis in the bone defect area;tartrate resistant acid phosphatase staining was performed to observe osteoclast differentiation;ELISA was performed to detect serum calcitonin and type I collagen C-terminal peptide levels;and Micro-CT and hematoxylin-eosin staining were performed to observe osteogenesis in the middle and late stages. RESULTS AND CONCLUSION:The number of tibial trabeculae was reduced and the trabeculae were sparsely arranged in the high iron ovariectomized group.Iron levels in the liver,jaw bone and serum were significantly higher in the high iron ovariectomized group than the sham-operated group at 2 weeks after bone grafting,while the iron levels were significantly decreased after deferoxamine mesylate intervention(P＜0.05).In the early stage of bone defect repair,more inflammatory cell infiltration,less new bone matrix and less type I collagen fiber production were observed in the high iron ovariectomized group than in the sham-operated group(P＜0.05);after deferoxamine mesylate treatment,inflammatory cell infiltration was reduced,a small amount of new bone matrix was produced and collagen fibers increased significantly(P＜0.05).In the middle and late stages of bone defect repair,Micro-CT results showed a reduction in new bone production in the high iron ovariectomized group compared with the sham-operated group and increased new bone matrix after deferoxamine mesylate treatment(P＜0.05).Compared with the sham-operated group,the osteoclast number,serum calcitonin level,and serum type I collagen C-terminal peptide level were increased in the high-iron ovariectomized group,while the osteoclast number was decreased and bone metabolic indexes were improved after treatment with deferoxamine mesylate.To conclude,in ovariectomized rats with high iron intervention,elevated iron levels can be seen in multiple tissues,accompanied by reduced new bone production in the mandibular bone defect area.Deferoxamine mesylate can improve bone metabolism and inhibit osteoclast activity by removing iron deposits in tissues,improve bone formation in iron-accumulated osteoporotic rats,and promote bone healing in the mandibular bone defect area.

OBJECTIVE To evaluate the effictiveness and safety of recombinant human endostatin combined with afatinib and teggio in the treatment of advanced lung squamous cell carcinoma. METHODS A total of 25 patients with driver-negative advanced lung squamous cell carcinoma were included in this single-arm prospective study, and the enrolled patients were treated with recombinant human endostatin combined with afatinib and teggio as scheduled. Progression-free survival(PFS), overall survival(OS), disease control rate(DCR), objective response rate(ORR), and adverse reactions(AR) were observed and analyzed. RESULTS The 25 enrolled patients received at least 2 cycles of second-line treatment, and were followed up as of March 31, 2023. Among them, 4 patients had partial remission, 17 patients had stable disease, and 4 patients experienced progressive disease. The ORR confirmed by the researchers was 16%(95%CI, 4.5%−36.1%), DCR was 84%(95%CI, 63.9%−95.5%), and median PFS was 5.3 months(95%CI, 3.5−6.9 months). The median OS had not yet been achieved. The entire group of patients had good treatment tolerance, and the most common level Ⅲ or Ⅳ adverse events related to treatment were leukopenia(20%) and rash(12%), with no reported treatment-related deaths. CONCLUSION Recombinant human endostatin combined with afatinib and teggio in the second line treatment of advanced lung squamous cell carcinoma can prolong the progression free survival period of patients and is relatively safe, which is worth further exploration and promotion.

Background China's automobile manufacture is a labor-intensive industry, and most of the welding tasks are manual operations. It is often necessary to observe the solder joints during operation, and there are many adverse health outcome-related factors involved in the work process. However, the research on the prevalence and risk factors of work-related musculoskeletal disorders (WMSDs) in the upper back of welders is still insufficient. Objective To explore the prevalence and risk factors of WMSDs in the upper back of welders from an automobile factory. Methods This was a cross-sectional study. A cluster random sampling method was used to select 972 electric welders from an automobile factory as the study subjects. The Musculoskeletal Disorders Questionnaire was used to estimate the prevalence of WMSDs in the upper back in the past year. Results The prevalence rate of WMSDs in the upper back in the welders was 42.2% (410/972). The positive rates of studied occupational risk factors were 72.5% (705/972) for maintaining same posture for a long time, 71.8% (698/972) for bending and twisting for a long time, and 64.7% (629/972) for repetitive trunk movements. The univariate analysis showed that the prevalence rates of WMSDs were significantly different among workers categorized by gender, working age, twisting and/or bending for a long time, working in the same position for a long time, lifting heavy objects in an uncomfortable position, repetitive trunk movements, being unable to exert energy due to discomfort, work involving cold or temperature changes, personnel shortage, no rest between work, working hours per week, and working in an uncomfortable position (P<0.05). The results of multiple logistic regression indicated that female, working in the same position for a long time, working in an uncomfortable position (frequently), lifting heavy objects in an uncomfortable position, and being unable to exert energy due to discomfort were associated with higher risks of reporting WMSDs in the upper back (OR=2.37, 1.46, 1.76, 1.44, and 1.50, respectively, P<0.05); the risk of reporting WMSDs in the upper back increased by 95%, 157%, and 196% for every 10 h increase in weekly working hours (41-50 h, 51-60 h, ≥61 h vs ≤40 h); adequate rest time was associated with a lower risk for WMSDs in the upper back (OR=0.70, 95%CI: 0.49-0.98). Conclusion The prevalence rate of WMSDs in the upper back of welders in the automobile factory is high, and many occupational risk factors are involved. Measures should be taken for intervention and prevention.

OBJECTIVE To study active components and antitussive effect of aboveground part of Pinellia ternata （non- medicinal stems and leaves）， and compare them with the underground part of P. ternata （medicinal underground tubers）， providing scientific basis for the comprehensive utilization and product development of P. ternata. METHODS TLC， GC， HPLC and UPLC- MS/MS were used for qualitative and quantitative analysis of amino acids， volatile oil， total flavonoids and succinic acid from the aboveground and underground parts of P. ternata. The antitussive effects of the aboveground and underground parts of P. ternata were compared and studied through cough inducing experiment with concentrated ammonia water. RESULTS Results of TLC showed that at the corresponding positions on the chromatograms of the reference substances of P. ternata， and arginine， alanine， valine， leucine and rutin control， the aboveground and underground parts of P. ternata showed spots of the same color. Results of GC showed that the similarity among characteristic chromatograms of volatile oil from aboveground and underground parts of P. ternata was 0.767； results of HPLC and UPLC-MS/MS showed that compared with underground parts of P. ternata， the contents of succinic acid， quercetin， kaempferol and isorhamnetin increased by 0.15%， 0.15%， 0.09% and 0.03%， and aspartate content decreased by 2.5 mg/g. Pharmacodynamics results showed that compared with model control group， the cough incubation period of rats was prolonged significantly in administration groups （P＜0.05）， and the cough frequency within 3 min was significantly decreased （P＜0.05）； there was no statistical significance in the cough frequency within 3 min among administration groups （P＞0.05）. CONCLUSIONS The composition of amino acids， volatile oils and total flavonoids in aboveground part of P. ternata are similar to underground part of P. ternata， while the content of aspartic acid is lower than that in underground part. The aboveground part of P. ternata can prolong the cough incubation period of rats and reduce the number of coughs， which has a certain antitussive effect， but the effect is slightly weaker than that of the underground part.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.003.].

Animals ; Epithelial Cells ; Epithelial-Mesenchymal Transition/genetics* ; MicroRNAs/genetics* ; Rats ; Rats, Inbred SHR ; Transforming Growth Factor beta/genetics* ; Transforming Growth Factor beta1/pharmacology*

Cardiovascular diseases account for approximately 80% of deaths among individuals with diabetes mellitus, with diabetic cardiomyopathy as the major diabetic cardiovascular complication. Hyperglycemia is a symptom that abnormally activates multiple downstream pathways and contributes to cardiac hypertrophy, fibrosis, apoptosis, and other pathophysiological changes. Although glycemic control has long been at the center of diabetes therapy, multicenter randomized clinical studies have revealed that intensive glycemic control fails to reduce heart failure-associated hospitalization and mortality in patients with diabetes. This finding indicates that hyperglycemic stress persists in the cardiovascular system of patients with diabetes even if blood glucose level is tightly controlled to the normal level. This process is now referred to as hyperglycemic memory (HGM) phenomenon. We briefly reviewed herein the current advances that have been achieved in research on the underlying mechanisms of HGM in diabetic cardiomyopathy.
Cardiovascular Diseases ; Diabetes Complications ; Diabetes Mellitus ; Diabetic Cardiomyopathies/etiology* ; Humans ; Hyperglycemia/metabolism* ; Multicenter Studies as Topic