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.

To introduce a strategy for a case of severe pneumonia complicated with lung abscess caused by Fusobacterium necrotum.The pathogen was not identified,but the patient was still coughing up feverish bloody sputum after being treated with meropenem,linezolid and ornidazole.The results of detection of pathogen metagenomes in bronchoalveolar lavage fluid by posterior bronchoscopy suggested that the pathogen was Fusobacterium necrophorum,according to the characteristics of bacteria,the dynamic changes of clinical symptoms,liver and kidney function,body temperature and blood picture infection index,combined with the results of bacterial culture/drug sensitivity test,bronchoalveolar lavage fluid NGS and the pharmacokinetic/pharmacodynamic characteristics of antimicrobial agents,to propose an anti-infective regimen that is strategically adjusted to imipenem cilastatin(1.0 g,ivd,q8h)plus ornidazole(0.5 g,ivd,q12h)for the implementation of pharmaceutical care after adoption by physicians.After 21 days,the patient's severe infection and lung abscess was controlled and patient was discharged.In this case,clinical pharmacists study the bacterial characteristics of Fusobacterium necrotum,review a large number of domestic and foreign literature to track the frontier knowledge of antimicrobial agents,and use their own expertise to provide effective pharmaceutical support for the clinical team,to assist clinical team in the diagnosis and treatment of rare infections,to achieve professional value.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

Objective To investigate the effects of Shenqi Tiaoshen Formula(SQTSF)for alleviating airway inflammation in rats with both chronic obstructive pulmonary disease(COPD)and lung-kidney qi deficiency syndrome and explore its therapeutic mechanism.Methods Forty-eight SD rats were randomly divided into control group,model group,low-,medium-,and high-dose SQTSF groups,and aminophylline(APL)group.In all but the control group,rat models of COPD with lung-kidney qi deficiency syndrome were established and treated with saline,SQTSF or APL via daily gavage as indicated(starting from day 30).The rats were observed for changes in body weight,grip strength,lung function,lung pathology,inflammatory cytokines in bronchoalveolar lavage fluid(BALF),oxidative stress levels,iron ion metabolism,cellular and mitochondrial ultrastructural changes in the lung tissue,and expressions of Nrf2/SLC7A11/GPX4 signaling pathway and ferroptosis-related proteins.Results The rats in the model group exhibited obvious symptoms of lung-kidney qi deficiency syndrome with significantly decreased body weight,grip strength,and lung function parameters.Examination of the lung tissue revealed showed significant inflammatory cell infiltration and emphysema with obvious bronchial,perivascular,and alveolar inflammation and alveolar destruction,significantly increased IL-1β,TNF-α,IL-6,and IL-13 levels in BALF,and elevated pulmonary oxidative stress levels and Fe2+and total iron ion concentrations.The rat models also showed characteristic ultrastructural changes of ferroptosis in the lung tissue cells under transmission electron microscope and significantly decreased Nrf2,GPX4,and SLC7A11 and increased ACSL4 expressions in the lung tissue.Treatment with SQTSF significantly improved these pathological changes in the rat models with a better effect than APL.Conclusion SQTSF can effectively improve airway inflammation and oxidative stress in COPD rats with lung-kidney qi deficiency possibly by inhibiting ferroptosis via regulating the Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo establish and evaluate a chronic obstructive pulmonary disease （COPD） model with lung-spleen qi deficiency. MethodA rat model mimicking COPD with lung-spleen qi deficiency was established by the combination of cigarette smoking and intratracheal instillation of lipopolysaccharide （LPS） along with gavage of Sennae Folium infusion. Forty male SPF-grade SD rats were randomly assigned to blank， model， and low- （L-FXY）， medium- （M-FXY）， and high-dose （H-FXY） Sennae Folium infusion groups. Other groups except the blank group were exposed to daily cigarette smoke， with LPS administrated via intratracheal instillation on the 1st and 14th days. On the 28th day of modeling， the L-FXY， M-FXY， and H-FXY groups were administrated with Sennae Folium infusion at 5， 10， and 20 g·kg^-1， respectively， and at 4 ℃ for three weeks. The modeling lasted for 49 days. The general conditions （body mass， food intake， fecal water content， and anal temperature） and behaviors （grip strength test and tail suspension test） of rats in different groups were examined. The lung function， lung histopathology， D-xylose， amylase， and gastrin levels in the serum， interleukin（IL）-1β and IL-6 levels in the alveolar lavage fluid， levels of T-lymphocyte subsets （CD4⁺， CD8⁺， and CD4⁺/CD8⁺） in the peripheral blood， and thymus and spleen indices were measured. ResultTwo rats died in the H-FXY group. Compared with the blank group， both the M-FXY and H-FXY groups exhibited reduced body mass and food intake （P<0.01） and increased fecal water content （P<0.01）. The anal temperature in the H-FXY group was lower than that in the blank group （P<0.01）. The grip strength decreased in the modeling groups compared with the blank group （P<0.01）， and the duration of immobility in the tail suspension test increased in the M-FXY and H-FXY groups （P<0.05， P<0.01）. Compared with the blank group， the modeling groups showed reduced 0.3 second forced expiratory volume （FEV_0.3）， FEV_0.3/forced vital capacity （FVC）（P<0.01）， thickening of bronchial walls， proliferation of goblet cells， and the presence of emphysematous changes. In terms of gastrointestinal function， the M-FXY and H-FXY groups had lower levels of D-xylose， gastrin， and α-amylase than the blank group （P<0.01）. Regarding the immune and inflammatory indices， the M-FXY and H-FXY groups showed lower thymus and spleen indices than the blank group （P<0.01）. Compared with the blank group， the modeling groups presented lowered CD4⁺ level （P<0.01） and CD4⁺/CD8⁺ ratio （P<0.05， P<0.01） in the peripheral blood and elevated levels of IL-1β and IL-6 in the alveolar lavage fluid （P<0.01） than the blank group. ConclusionA model of COPD with lung-spleen Qi deficiency was established through the combination of daily cigarette smoke， intratracheal instillation with LPS， and gavage of Sennae Folium infusion. The comprehensive evaluation results suggested medium-dose （10 g·kg^-1） Sennae Folium infusion for gavage during the modeling of COPD with lung-spleen Qi deficiency.

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.

Objective To understand the epidemiological characteristics of the cases of COVID-19 epidemic clusters, and explore the influence of family factors and social factors such as group activities on the spread of the disease. Methods The data of cases of COVID-19 epidemic clusters from 19 January, 2020 to 25 February, 2020 were collected from the official platforms of 36 cities in 6 provinces in China. Descriptive statistical methods, χ 2 test and curve fitting were used to analyze the epidemiological characteristics of the clustered cases. Results By 25 February, 2020, the data of 1 052 cases in 366 epidemic clusters were collected. In these clustered cases, 86.9%(914/1 050) occurred in families. Among the 1 046 cases with gender information, 513 were males (49.0%) and 533 were females (51.0%). The cases were mainly young adults between 18 and 59 years old, accounting for 68.5% (711/1 038). In the 366 epidemic clusters , the clusters in which the first confirmed cases with the history of sojourn in Wuhan or Hubei accounted for 47.0%(172/366). From 19 January to 3 February, 2020, the first confirmed cases with Wuhan or Hubei sojourn history accounted for 66.5%. From 4 to 25 February, the first confirmed cases who had Wuhan or Hubei sojourn history accounted for only 18.2%. The median of interval between the first generation case onset and the second generation case onset was 5 (2-8) days. The median of onset- diagnosis interval of the initial cases was 6 (3-9) days, and the median of onset-diagnosis interval of the secondary cases was 5 (3-8) days. Conclusions Epidemic clusters of COVID-19 were common in many cities outside Wuhan and Hubei. Close contact in family was one of the main causes for the spread of household transmission of the virus. After 4 February, the epidemic clusters were mainly caused by the first generation or second generation cases in local areas, and the time for diagnosis became shorter.

OBJECTIVE: Poly (ADP-ribose) polymerase (PARP) is an important molecule in the early stress response of DNA damage, which is involved in DNA damage repair and cellular senescence. Olaparib, as PARP inhibitor, has an anti-tumor effect on high grade serous ovarian cancer, but its effects on cellular senescence have not been reported. This study intends to explore the role of olaparib in the regulation of senescence in ovarian cancer cells. METHODS: The effects of olaparib on the senescence of ovarian cancer cells were detected by using the senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated heterochromatin aggregation (SAHF). Quantitative real-time polymerase chain reaction was used to analyze the senescence-associated secretory phenotype (SASP). Cell cycle and apoptosis were detected by flow cytometry. The effect of olaparib on tumor growth was analyzed in a nude mouse xenograft transplantation model. RESULTS: Long-term (6 days) treatment with olaparib (5 μM) significantly inhibited the growth of ovarian cancer cells, leading to arrest the cell cycle at G0/G1 phase, significant increase the number of positive SA-β-Gal stained cells and positive SAHF cells. The expression of P16 and retinoblastoma protein (p-RB) were significantly enhanced in SKOV3 cells under olaparib treated, meanwhile, the expression of P53 and p-RB were upregulated in A2780 cells. In OVCAR-3 cells, the expression of P53 was downregulated and p-RB was upregulated. Mice with SKOV3 xenograft transplantation was given olaparib (10 mg/kg/day) via abdominal cavity administration, the tumor volume was reduced (p < 0.01). CONCLUSION: Continuous low dosage administration of olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer.
Abdominal Cavity ; Aging ; Animals ; Apoptosis ; Cell Aging ; Cell Cycle ; DNA Damage ; Flow Cytometry ; Heterochromatin ; Mice ; Mice, Nude ; Ovarian Neoplasms ; Phenotype ; Real-Time Polymerase Chain Reaction ; Retinoblastoma Protein ; Transplantation, Heterologous ; Tumor Burden

Objective To assess the value of shear-wave elastic modulus for differential diagnosis of benign and malignant breast lesions using Meta-analysis.Methods Relevant Chinese and foreign articles about shear-wave elastography for differentiating benign and malignant breast lesions were collected from the literatures published before Apr.2016.Meta-analysis was conducted to assess the overall ability of the shear wave elastic modulus including Emax,Emea,Eratio and Esd.Results Totally 31 studies were brought into the Meta-analysis.The summarized sensitivity (SSEN) and summarized specificity (SSPE) of Emax were 0.87(95％CI [0.83,0.91]) and 0.91 (95％CI [0.87,0.93]).The SSEN and SSPE of Emea were 0.84 (95％CI [0.77,0.89]) and 0.88 (95％CI [0.84,0.91]),The SSEN and SSPE of Eratio were 0.88(95％CI [0.83,0.91]) and 0.87 (95％CI [0.80,0.91],the SSEN and SSPE of gsd were 0.85 (95％CI [0.80,0.89]) and 0.90 (95％CI [0.85,0.94]).The summarized receiver operator characteristic analysis showed that the area under the curve of E E Eratio and Esd were 0.95,0.93,0.93 and 0.93.Conclusion The shear wave elastic modulus contribute to differentiate benign and malignant breast lesions.Among these indices,Emax is the best one.