With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Objective:To explore the clinical effects of free anterolateral thigh perforator flap (ALTPF) with modified cross-leg vessel bridging in reconstruction of infected wounds in the lower leg combined with major vessel defects.Methods:A retrospective observational study was conducted on 7 patients who admitted to the Department of Trauma Orthopaedics, the 521 Hospital of Norinco Group from January 2020 to December 2021 for treatment of large infected wounds in lower leg with soft tissue defect by reconstructive surgery of flap transfer. The patients were 5 males and 2 females, aged 23-50 years old with an average age of 37 years old. The causes of injury were: 5 patients were of car accidents, 1 of machinery compression and 1 of heavy object crush. The wounds were reconstructed after debridement and infection control with sensitive antibiotics, where the soft tissue defects were found at 11.0 cm×15.0 cm to 20.0 cm×32.0 cm in size. All patients underwent vascular angiography or CDU examinations and it was confirmed that the affected calf had only an anterior tibial artery as the vessel left for blood supply in 6 patients and a posterior tibial artery as the blood supply vessel in one patient. Therefore application of vascular end-to-side anastomosis in free flap reconstruction of limb defects was impossible due to the damaged artery could not be salvaged as a blood supply artery for the transferred flap. Therefore, a modified cross-leg vessel bridging to the freed ALTPF in the affected lower leg was applied. The donor site of the pedicle was covered with VSD while the pedicle of the flap was anastomosed. It was remained until the posterior tibial artery and the tubular flap were ready for replantation after disconnection of the pedicle. The sizes of flap were 13.0 cm×17.0 cm to 22.0 cm×32.0 cm (unilateral ALTPFs for 6 patients and bilateral ALTPFs for 1 patient). Two donor sites in low tension were direct closed, and the rest of 5 donor sites that had great tensions and could not be directly sutured were reconstructed by skin grafting. The survival and complications of flaps were observed in the scheduled postoperative follow-ups at outpatient visits, WeChat reviews and home visits, etc.Results:All 7 patients were successfully treated and had 12-24 months postoperative follow-up, with an average of 16 months. All flaps survived, with primary healing in 6 patients and 1 patient had partial flap necrosis with surface infection, which healed after dressing changes. The wound healing time was 14-36 days with an average of 17.9 days. The time for disconnection of the cross-leg vessel bridging pedicle was 3-4 weeks with the flap transfer, with an average of 3.6 weeks. The donor sites of ALTPFs and vessel pedicles all healed well. CDU confirmed the patency of the contralateral posterior tibial artery. Satisfactory functional recovery was achieved in the affected lower limb and there was a good function of the contralateral healthy lower leg.Conclusion:Application of the transfer of a free ALTPF with modified cross-leg vessel bridging in reconstruction of infected wounds with major vessel defects in the lower leg has shown excellent clinical outcomes. It is a practical and effective method in treatment of large infective defect in lower leg.

ObjectiveTo explore the clinical efficacy and safety of Qifu Yixin prescription in treating chronic heart failure in the patients with the syndrome of heart Qi deficiency， so as to provide clinical evidence for the treatment of chronic heart failure with this prescription and promote the clinical application and transformation of this prescription. MethodA total of 106 chronic heart failure patients with the syndrome of heart Qi deficiency who met the criteria in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine （TCM） from September 2022 to May 2023 were selected and randomized into an observation group （53 cases） and a control group （53 cases）. Both groups received routine Western medicine treatment. In addition， the observation group received Qifu Yixin prescription， while the control group received placebo. The treatment course for both groups was 12 weeks. The New York heart association （NYHA） cardiac function grading， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth-stimulating expression gene 2 （sST2）， left ventricular ejection fraction （LVEF）， the ratio of early diastolic maximum mitral flow velocity （E） to early diastolic mitral annular motion velocity （e'） （E/e'）， left ventricular end diastolic diameter （LVEDD）， TCM syndrome scores， 6-minute walking test （6MWT）， Minnesota Living with Heart Failure Questionnaire （MLHFQ）， and Kansas City Cardiomyopathy Questionnaire （KCCQ） were determined before and after treatment. ResultFinally， 102 patients were included for analysis， including 51 patients in the observation group and 51 patients in the control group. After treatment， 42 patients in the observation group showed improved cardiac function grading， with a total response rate of 82.35%， and 32 patients in the control group showed improved cardiac function grading， with a total response rate of 62.75%. The total response rate regarding the cardiac function in the observation group was higher than that in the control group （χ²=4.923， P<0.05）. The observation group outperformed the control group in lowering the NT-proBNP level， elevating LVEF， decreasing the E/e' ratio （P<0.05）， reducing LVEDD and sST2 levels， and recovering TCM syndrome score， 6MWT score， MLHFQ score， and KCCQ score （P<0.05）. None of the safety indexes in the two groups showed abnormal values before and after treatment， and no serious adverse reaction was observed. ConclusionQifu Yixin prescription can improve the heart function， exercise tolerance， and quality of life and alleviate the TCM syndrome of the chronic heart failure patients with the syndrome of heart Qi deficiency by inhibiting myocardial fibrosis.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

ObjectiveTo understand the current situation and influencing factors of health service demands of new residents in Shanghai. MethodsFrom July to August 2020， a questionnaire survey was conducted in 1 358 new residents from 36 survey points in 7 districts of the city. The questionnaire included the basic medical insurance coverage in the inflow area， the current situation of medical demand and related influencing factors， and the demands for other health services. Results47.1%（562/1 194）of new residents did not choose to seek timely medical treatment when they were not feeling well. The main reason was that the working hours occupied the medical treatment time. Logistic regression analysis showed that the main factors affecting the medical needs in new residents were the average daily working hours， living area and type of residence， health status， physical examination and physical exercise， and the type of basic medical insurance. The demands of new residents for "health consultation of common diseases and frequently occurring diseases"， "health behavior intervention （such as smoking cessation and alcohol restriction）"， "medical guidance and publicity"， "accidental injury prevention （traffic， work， falling， etc.）" and "maintenance of legitimate rights and interests of health" were 57.1%（682/1 194）、41.3%（493/1 194）、34.9%（417/1 194）、32.2%（385/1 194） and 31.9%（381/1 194）， respectively. ConclusionNew residents demands for medical services cannot be met. We should actively improve the working and living conditions of new residents， improve the construction of new residents' health service system， and improve the utilization level of health services.

Objective:To evaluate the clinical value of 5.0 T ultra-high filed MRI system in assessing intracranial arteries segments and vessel branchers.Methods:This study was a prospective study. Totally 40 consecutive healthy volunteers were recruited from Zhongshan Hospital, Fudan University from September 1, 2021 to November 30, and all participants who underwent either 3.0 T or 5.0 T time-of-flight MR angiography (TOF-MRA) in random order were divided into 3.0 T MR group and 5.0 T MR group with 20 volunteers for each group. Image quality was assessed by Likert 5 scoring systems and signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR),and score in visualization of intracranial arteries [middle cerebral artery (MCA) and its segments, anterior cerebral artery (ACA) and its segments, posterior cerebral artery (PCA) and its segments, lenticulostriate arteries (LA) and pontine artery (PA)] were assessed from 0 to 3 (≥2: good depiction of vessel segment). Quantitative indicators were compared between 2 groups using independent t test or Mann-Whitney U test. Results:Among the 40 subjects, there were 29 males and 11 females, aged 20-69 (50±12) years. SNR and CNR were both significantly higher in 5.0 T MR group than those in 3.0 T MR group (SNR: 187±9 vs 91±4, t=31.59, P<0.001; CNR: 156±7 vs 70±4, t=31.45, P<0.001), but there was no significant difference in subjective scores of image quality between the 5.0 T MR and 3.0 T MR groups [5.0 (4.0, 5.0), 5.0 (5.0, 5.0) points, respectively, Z=-1.23, P=0.218]. In the evaluation of cerebral arteries, the visualizations of the proximal and middle segments of MCA, ACA and PCA was better than those in the 3.0 T MR group, and there was no significant difference in the scores ( P>0.05), while the visualizations of proximal arteries in the 5.0 T MR group were significantly better than those in the 3.0 T MR group ( P<0.05). Furthermore, small vessel branches such as LA and PA in 5.0 T MR group were visualized better than those in 3.0 T MR group ( P<0.001). Conclusion:TOF-MRA by ultra-high filed 5.0-T provides an optimal choice in visualization of distal large arteries and small vessel branches, which could be useful for the diagnosis on cerebral vascular disease.

Objective:To investigate the clinical effect of gracilis musculocutaneous flap in repair of perineal soft defect with open pelvic fracture.Methods:From June 2009 to June 2019, 11 cases of open pelvic fracture associated with perineal injury were treated in the Department of Trauma and Orthopaedic of 521 Hospital of Norinco Group. There were 4 males and 7 females aged 16-56 (33 in average) years old. Cause of injuries: 6 cases by traffic accident, 4 by falling from height, and 1 by crushing. All the patients had open pelvic fractures. According to Tile classification, 1 case was rated as type A, 7 as type B and 3 as type C. All the patients were accompanied with perineal injury and soft tissue defect. The wound sizes ranged from 5 cm×5 cm to 8 cm×12 cm. The defects were repaired with gracilis musculocutaneous flap. The size of gracilis myocutaneous flaps was 6 cm×5 cm to 9 cm×13 cm. All donor areas of the flap were sutured directly. After surgery, 11 patients treated with strengthened nutritional support, keep supine position to avoid abduction, and appropriately raise the lower limbs. Follow-ups were conducted regularly after surgery.Results:All patients entered 6 to 30 (22 in average) months of follow-up. All of 11 myocutaneous flaps survived, besides 1 had a few necrosis at the distal surface of the myocutaneous flap, and healed after change of dressing. All the incisions at donor site had stage I healing. The colour, texture and flexibility of the gracilis myocutaneous flap were good. There was a scar at the donor sites without causing obvious dysfunction. Over the follow-up period, there was no failure of flap in either the recipient and donor sites. The patients were satisfied with the appearance and function.Conclusion:Gracilis musculocutaneous flap is one of the ideal methods in repair of perineal soft tissue defect with open pelvic fracture.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Objective: To explore the clinical application and effect of free fibula composite tissue flap trans-plantation to repair bone and soft tissue defect after open fracture of proximal tibial. Methods: From June, 2012 to June, 2018, free fibula composite tissue flap transplantations were applied to repair bone and soft tissue defect after open fracture of proximal tibial in 11 cases. Of the 11 cases, there were 10 males and 1 female(their ages ranged from 32 to 56, 36 on average); Six cases were caused by traffic accident, and 5 by crash. There were 3 fresh wounds and 8 chronic and infective wounds. Free fibular flaps were used in 7 cases, and free fibular flexor hallucis myocutaneous flaps were used in 4 cases. The fibular length with transplantation was 7-18 cm. The area of flaps or muscle flaps was ranged from 4 cm×8 cm to 8 cm×20 cm. Bone fracture healing was observed at 3, 6 and 12 months after operation. The function of injured extremity was evaluated in 1 year after surgical operation. Results: All were successfully repaired, and composite tissue flaps survived. Of which, 10 wounds healed by first intention, and 1 wound healed by secondary intention, with the healing time of 12-18 days. All 11 cases were followed-up. The mean followed-up time was 18 months. The bone healing time ranged from 6 to 9 months (7 months on average). The Enneking Score System was applied to evaluate the leg function. Of the 11 cases, the mean scores was 25 (ranged from 22 to 27). The donor sites were not found malfunctional. Conclusion Transplantation of free fibula composite tissue flap can reduce the treatment time with good mechanical strength. It is an ideal method to repair bone and soft tissue defect after open fracture of proximal tibial.