Objective To evaluate the effectiveness,safety and economy of the clinical application of levetiracetam(LEV)concentrated solution for injection generic drug and the original drug in the national centralized volume-based procurement.Methods The information of inpatients using original LEV concentrated solution for injection in the Xuanwu Hospital of Capital Medical University(original drug group)and inpatients using generic LEV concentrated solution for injection in the First Affiliated Hospital of Wannan Medical College(generic drug group)was retrospectively analyzed after the implementation of the procurement policy(from November 2021 to March 2022).To compare the effectiveness,safety and economy of the two in the prevention and treatment of epilepsy.Results In the original drug group and the generic drug group,18 and 17 patients were enrolled in the treatment of epilepsy respectively,the effective rates were 50.00％and 58.82％,the incidence of adverse reactions were both 0％,and the median daily cost was 255.00(255.00,510.00)yuan and 131.78(131.78,131.78)yuan.After propensity score matching,both the original drug group and the generic drug group had 76 patients each received preventive medication,the effective rates were 97.37％and 100％(P＞0.05),and the incidence of adverse reactions were both 0％.The median daily fee for the original the generic drug group was 170.00(170.00,170.00)yuan and 131.78(131.78,131.78)yuan,there were significant difference(P＜0.01).Conclusion The clinical effect of generic and original LEV concentrated solution for injection in preventing epilepsy is basically the same,the clinical safety are equivalent,the generic has better economy than the original.The effective rate of the treatment of epilepsy is similar,while the sample size needs to be further expanded to verify the results.

Objective:To investigate the effects of inhibition of Wnt/ β-catenin signaling pathway on paraquat (PQ)-induced transition of human lung fibroblast cell line MRC-5 and related molecular mechanisms.Methods:The MRC-5 cells were divided into three groups. Control group: without drug treatment; PQ group: the cells were treated by PQ (50 μmol/L) for 72 hours to establish cell transition model; PQ+DKK1 group: the cells were treated with PQ (50 μmol/L) and DKK1 (10 ng/mL) for 72 hours. Then, the cells were collected, and the transition related signatures including α-SMA, Vimentin and Collagen I were detected by immunofluorescence and Western blot (WB); Meanwhile, the expression levels of Wnt pathway-related molecules including β-catenin, Cyclin D1 and WISP1 were determined by WB, immunofluorescence and real-time fluorescence quantitative PCR (RT-PCR) during the transition; In addition, the inhibitor of Wnt/β-catenin pathway Dickkopf-1 (DKK1) was applied to block the signaling. Then the expression changes of β-catenin, cyclin D1 and WISP1 were detected by WB to verify the inhibitory effect, and the transition marker molecules including α-SMA, Vimentin and Collagen I were also determined by WB.Results:After 72 hours, compared with the Control group, the expression levels of α-SMA, Vimentin and Collagen I of MRC-5 cells in PQ group were increased significantly ( P<0.05); The expression levels of β-catenin, Cyclin D1 and WISP1 of MRC-5 cells in PQ group were significantly up-regulated ( P<0.05); DKK1 could inhibit the high expression of α-SMA, Vimentin and Collagen I of MRC-5 cells during PQ-induced transition ( P<0.05). Conclusions:DKK1 could inhibit PQ-induced transition of lung fibroblasts by interference with Wnt/β-catenin signaling, which was expected to further inhibit pulmonary fibrosis caused by PQ.

Objective To understand the status of sexually transmitted infection and seeking medical treatment behavior, and influencing factors of Vietnamese cross-border female sex workers (FSWs) in Hekou County, Yunnan, and to provide a basis for promoting reproductive health and preventing and controlling the spread of sexually transmitted diseases (STD) in Vietnamese cross-border FSWs. Methods The snowball sampling method was used to recruit research subjects in entertainment venues in Hekou County, Yunnan, to conduct a questionnaire survey and collect blood, vaginal secretions and cervical swab specimens for HIV/STD testing. Results A total of 262 Vietnamese cross-border FSWs were investigated. The total infection rate of sexually transmitted diseases and HIV was 35.8% (94/262). The positive rate of genital herpes simplex, fungal vaginitis, trichomoniasis, wet warts and chlamydia were 23.5%, 8.0%, 2.7%, 1.5% and 1.5%, respectively. The positive rate of HIV was 1.5%. In the past year, 116 Vietnamese cross-border FSWs had symptoms related to sexually transmitted diseases. Among them, 34.5% chose to go to the hospital or private outpatient clinic, 44.8% bought medicines by themselves, and 20.7% did not receive any treatment. The FSWs who reported having sexually transmitted diseases testing in the past year (OR=3.54, P<0.05), came from medium and high-end places (OR=3.94, P<0.05), had more than two symptoms (OR=3.88, P<0.05), and self-perceived high risk of sexually transmitted infection were more likely to seek medical treatment. Conclusion The Vietnamese cross-border FSW population in Hekou County of Yunnan Province had a high rate of sexually transmitted infections. The proportion of seeking medical treatment among FSWs having symptoms related to sexually transmitted diseases was low. It is necessary to guide the Vietnamese cross-border FSWs to seek formal medical treatment.

Auditory neuropathy (AN) is a hearing disorder where cochlear inner hair cell and/or the auditory nerve function is disrupted while outer hair cell function is normal. It can affect people of all ages, from infancy to adulthood. People with auditory neuropathy may have normal hearing threshold, or hearing loss ranging from mild to severe; they always have poor speech-perception abilities. It is a heterogeneous disorder which can have either congenital or acquired causes. AN may result from specific loss of cochlear inner hair cells, disordered release of neurotransmitters by inner hair cell ribbon synapses, deafferentation accompanying loss of auditory nerve fibers, neural dys-synchrony or conduction block as a result of demyelination of nerve fibers and auditory nerve hypoplasia. Although the definition of AN includes the central part, its incidence is low, and the etiology and pathology are not clear. The present review aimed to provide an overview of the genetic conditions associated with AN and highlight the neural and synaptic mechanism of AN. Possible strategy for treatments of AN was also discussed.

Objective To investigate the value of the reverse shock index multiplied by GlasgowComa scale score (rSIG) and serum translocator protein 18000 in the prognosis of patients with severe traumatic brain injury. Methods One hundred and fifteen patients with severe traumatic brain injury were divided into the survival group and death group. SPSS 20.0 software was used to compare the vital signs, rSIG and TSPO between the two groups, and the relationship between rSIG and TSPO was analyzed. Receiver operating characteristic (ROC) curve was used to predict the value of rSIG and TSPO and their combination in the prognosis of patients with severe traumatic brain injury. According to the best cut-off value of rSIG and TSPO of ROC curve, patients were divided into the rSIG ≤ 14.8 group and rSIG>14.8 group, and the TSPO ≤ 1.84 ng/mL group and TSPO>1.84 ng/mL group, and the mortality between the groups was compared. Results In 115 patients, rSIG of the survival group was significantly higher than that of the death group, and TSPO was significantly lower than that of the death group [(10.5±4.4) vs. (6.4±4.1), 1.0(0.3,1.9) ng/mL vs.3.4 (2.0, 4.6) ng/mL, P<0.01]. The ability of rSIG combined with TSPO to forecast the mortality of patients with severe traumatic brain injury is not superior to the predictive power of these two indicators alone. The serum TSPO value and 28-day mortality in the rSIG > 4.15 group were significantly higher than those in the rSIG ≤ 4.15 group. The rSIG value of the TSPO ≤ 1.84 ng/mL group was significantly higher than that of the TSPO>1.84 ng/mL group; the 28-day mortality was significantly lower than that in the TSPO>1.84 ng/mL group. The rSIG value was negatively correlated with serum TSPO value (r=-0.611, P<0.01). Conclusions rSIG value and serum TSPO value have good predictive value for the prognosis of patients with severe traumatic brain injury, and can provide certain guiding significance in clinical practice.

Objective To investigate the value of D-dimer plus injury severity score (ISS) in predicting the prognosis of trauma patients. Methods The clinical data of 1 592 traumatic patients admitted to our emergency room from January 1, 2014 through December 31, 2016 were retrospectively analyzed. Excluding criteria included patients below the age of 14 and patients admitted over 24 h after injury, clinical death at admission, patients left from the hospital without the approval of attend doctor, detail and complete clinical data of patients not available, patients with history of coagulopathy, primary hepatic function failure, anticoagulants used within 6 months prior to injury, and patients with multiple injury affecting more than two parts of body. Finally, a total of 1 167 patients were enrolled in this study. The 28-day prognosis was used as the endpoint. The patients were divided into survival group and death group. The differences in venous plasma D-dimer and ISS at the fi rst detection between two groups were compared by Mann-Whitney U test. According to ISS, the patients were divided into mild injury group, moderate injury group and severe injury group. The Kruskal-Wallis one-way ANOVA test was used to compare the differences among different groups. Meanwhile, the area under the ROC curve was used to compare the accuracy of predictive effi ciency of D-dimer, ISS and the combination of both. Results There was a positive correlation between D-dimer and ISS, and D-dimer and ISS in survival group were significantly lower than those in death group(Z=-7.777, Z=-6.694, P <0.01). There was a statistically signifi cant difference in mortality among groups (χ2= 70.85, P <0.01); The area under the ROC curve of ISS, D-dimer and both combined was 0.728, 0.765, 0.800, respectively. The area under the ROC curve of D-dimer to predicte patients' prognosis was a little bit larger than that of ISS, but the difference was not statistically signifi cant (Z=1.051, P=0.293). The area under the ROC curve of joint both of them for the prognosis of the patients was greater than that of ISS or D-dimer alone( Z=3.028, Z=2.722, P<0.05). Conclusions The levels of D-dimer and ISS in patients with traumatic injury are correlated with the severity and mortality of patients. The increased D-dimer and ISS score indicates that the risk of death is increased, and prediction effi ciency of combining both of them is superior to either alone.

Objective: To develop a method for the determination of lacidipine (LAC) in human plasma.Methods: After liquid-liquid extraction with tert-butyl methyl ether, the plasma samples were analyzed by LC-MS/MS.Using lacidipine-13C8 as the internal standard, a Agilent ZORBAX Eclipse XDB C18 column (150 mm×2.1 mm, 5 μm) was used with the mobile phase consisting of water(containing 5 mmol·L-1 ammonium formate)-acetonitrile(15∶85,v/v)at a flow rate of 0.3 ml·min-1 and with the column temperature at 40 ℃.The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding + as the molecular ion peak of lacidipine and monitoring with m/z 473.5→m/z 410.3, m/z 473.5→m/z 400.1 and m/z 473.5→m/z 354.3.The internal standard was monitored with m/z 481.4→m/z 362.3.Results: The linear range of lacidipine was 0.1-10 ng·ml-1 (r＞0.99) and the lower quantification limit was 0.1 ng·ml-1.The intra-and inter-day RSDs were 3.15%-7.04% and the relative error was from-8.58% to 12.71%.The mean relative recovery of lacidipine was from 107% to 118% (RSD＜15%).The plasma samples were stable at-20℃ for 40 d and kept stable after three repeated freeze-thaw cycles.The prepared samples were stable at room temperature for 24 h and in the automatic sample injector (4℃) for 24 h(RSD＜15%).Conclusion: The developed assay method can be applied in the bioequivalence evaluation and pharmacokinetic studies of lacidipine in human.

BACKGROUND:Bone marrow mesenchymal stem cels are crucial for bone and cartilage development and regeneration at a celular level. Insufficient quantity and functional impairment of bone marrow mesenchymal stem cels is widely considered to be one of osteoarthritis causes. OBJECTIVE: To explore the relationship between the functional status of bone marrow mesenchymal stem cels and disease progression in osteoarthritis patients.METHODS: Thirty patients with osteoarthritis were enroled from July 2013 to October 2014, and divided into control, mild osteoarthritis, and severe osteoarthritis groups, with 10 cases in each group. 5 mL bone marrow from the femur or tibia was extracted from each patient to isolate and culture bone marrow mesenchymal stem cels. Proliferation ability of cels at passage 3 was detected using cel counting kit-8; toluidine blue staining was performed at 14 days after chondrogenic induction; real-time PCR was used to detect the mRNA expression of Aggrecan and Col2A1 in the control group after chondrogenic induction. RESULTS AND CONCLUSION:Afterin vitro culture, bone marrow mesenchymal stem cels grew adherently in polygonal and fusiform shape with multiple processes at uniform size. The cytoplasm contained larger particles and the nuclei were ovoid. Most of cels were in cel division phase. The proliferation ability was strongest in the control group and weakest in the severe osteoarthritis group. Cels from the three groups were al at plateau phase after 1 week culture. At 14 days after chondrogenic induction, the cels were polygonal and quasi-circular, and purple metachromatic granules distributed outside of the cytoplasm. The expression of Aggrecan and Col2A1 in the control group displayed an overexpression trend. These findings indicate that the functional status of bone marrow mesenchymal stem cels from osteoarthritis patients is negatively correlated with the severity of disease, which can influence the disease progression in osteoarthritis patients.

BACKGROUND:Since damage control theory system was founded, this theory in the orthopedics has been applied gradualy, especialy in elderly hip fracture surgery that reduces the negative impacts due to inflammatory responses. OBJECTIVE:To explore whether flurbiprofen axetil can reduce inflammatory responses in rats with hip fractures based on the damage control theory. METHODS: Forty-nine healthy Sprague-Dawley rats weighing 250-300 g were randomly divided into four groups:control group (n=7), immediate internal fixation group (n=14), flurbiprofen axetil group (n=14), damage control group (n=14). Rats in the control group moved freely in the cages. Rats in the other three groups were intraperitonealy injected with composite anesthetics to make unilateral hip fracture models, and then respectively given internal fixation immediately after fracture, flurbiprofen axetil injection and delayed internal fixation, and delayed internal fixation. Levels of serum C-reactive protein, interleukin-6 and tumor necrosis factor-α were determined and analyzed before fixation, immediately after internal fixation and at 4, 8, 12, 24, 48 hours after internal fixation in different groups. RESULTS AND CONCLUSION:Postoperative serum levels of C-reactive protein, interleukin-6, tumor necrosis factor-αwere al increased in different groups. The level of C-reactive protein reached the peak at 24 hours after internal fixation. Flurbiprofen axetil injection had no significant influence on the level of C-reactive protein in rats with delayed internal fixation (P=0.51). Interleukin-6 levels were stil increased at 48 hours after internal fixation, but flurbiprofen axetil reduced the level of interleukin-6 significantly in rats with delayed internal fixation (P < 0.01). The tumor necrosis factor-α level peaked at 4 hours after internal fixation, and flurbiprofen axetil injection could significantly reduce the level of tumor necrosis factor-α in rats with delayed internal fixation (P < 0.01). These findings indicate that flurbiprofen axetil as a new non-steroidal anti-inflammatory drug can reduce the inflammatory response in rats with hip fractures after internal fixation, and also can aleviate the inflammatory response of rats undergoing delayed operation under the guidance of damage control theory.

Objective To systematically evaluate the relationship between atherosclerotic renal artery stenosis (ARAS) and cor‐onary artery disease (CAD) and peripheral arterial disease (PAD) .Methods We gathered all case‐control studies about the correla‐tion of ARAS with CAD and PAD in the following databases:Cochrane library ,PubMed ,EMBASE ,Web of science until April , 2014 .Two reviewers extracted all relevant datas from the screened documents independently according to exclusion and inclusion criteria ,RevMan 5 .2 software were used to conduct Meta‐analysis .Results Fourteen trials were included .Meta‐analysis showed that :the OR (95% CI)of CAD with 1 vascular lesions ,2 vascular lesions ,3 vascular lesions and left main stenosis ,PAD and ARAS were 0 .70(0 .59-0 .82) ,1 .28(1 .10 -1 .48) ,2 .09(1 .69 -2 .59) ,1 .82(1 .40 -2 .36) ,3 .68(2 .21 -6 .10) with statistical signifi‐cance (P<0 .05) .Conclusion CAD with 2 vascular lesions ,3 vascular lesions and left main stenosis ,PAD were connected with ARAS ,CAD with 1 vascular lesions has little relationship with ARAS .