Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective: To investigate the expression of transient receptor polycystic protein 2(TRPP2) in oral squamous epithelial cell and its effect on the invasion and migration of oral squamous cell carcinoma(OSCC), and to explore the potential signaling pathway of TRPP2 affecting OSCC metastasis. Methods: The OSCC model with TRPP2 knockdown was constructed by CRISPR-Cas9 lentivirus plasmid transfection technique. The effect of TRPP2 protein knockdown was verified by Western blot. The effect of TRPP2 on OSCC proliferation was detected by CCK-8 assay and clone formation assay. RT-qPCR was used to detect the target genes associated with TRPP2 metastasis to OSCC. Western blot and RT-qPCR were used to detect the expression of EpCAM and its transcription factors associated with unfolded protein response(UPR). The effects of TRPP2 on the invasion and migration of OSCC were examined by invasion test and scratch test. Results: Compared with HOK in oral epithelial cells, the expression of TRPP2 in OSCC was significantly higher. When TRPP2 was knocked down, OSCC proliferation and clonalformation were significantly enhanced. Compared with the control group, a total of 494 differential genes were significantly expressed in TRPP2 knockdown transcription profile, among which 234 genes were up-regulated and 260 genes were down-regulated. The expression of EpCAM gene, which is related to cell adhesion, was up-regulated. In addition, UPR related genes PERK, ATF6, GRP78 were up-regulated, while ATF6 and EpCAM were down-regulated in OSCC compared to HOK cells. The expression of ATF6 and EpCAM in oral squamous cell carcinoma cells was up-regulated by TRPP2 knockdown, and the cell migration and invasion ability decreased. The ATF6 inhibitor ceapin-A7(5 μmol/L) restored the OSCC migration and invasion ability of TRPP2 knockdown. Conclusion TRPP2 is highly expressed in OSCC. When TRPP2 is knocked down, OSCC proliferation ability is enhanced, migration and invasion ability are inhibited. TRPP2 mediates the expression of EpCAM through activation of UPR, thus affecting the invasion and migration of oral squamous cell carcinoma.

Objective To observe the clinical efficacy of joint needling method combined with ultrasound in the treatment of qi stagnation and blood stasis type of patellofemoral pain syndrome(PFPS).Methods Eighty-six patients with qi stagnation and blood stasis type of PFPS were randomly divided into observation group and control group,with 43 cases in each group.The control group was given western medicine conventional treatment combined with functional exercise,and the observation group was given joint needling method combined with ultrasound treatment on the basis of the control group.Both groups were treated for 2 consecutive weeks.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in the Visual Analogue Scale(VAS)scores of knee pain and the Kujala scale scores of the two groups were observed before and after treatment.The changes in active range of motion(AROM)of the affected knee joint were compared before and after treatment between the two groups.Results(1)After treatment,the VAS scores of the two groups of patients were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of VAS scores,and the difference was statistically significant(P＜0.05).(2)After treatment,the Kujala scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of Kujala scores,and the difference was statistically significant(P＜0.05).(3)After treatment,the AROM of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the level of AROM,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 95.35%(41/43)in the observation group and 81.40%(35/43)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion The joint needling method combined with ultrasound can significantly relieve the pain symptoms of patients with PFPS and promote the recovery of knee joint function,and the clinical efficacy is remarkable.

AIM To establish a quantitative analysis of multi-components by single-marker(QAMS)method for the simultaneous content determination of gastrodin,parishin E,syringin,parishin B,parishin C,ferulic acid,parishin A,buddleoside,harpagoside and cinnamic acid in Tianma Toufengling Capsules.METHODS The analysis was performed on a 30℃thermostatic GL Science InertsilTM ODS-3 column(150 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 220,280 nm.Syringin was used as an internal standard to calculate the relative correction factors of the other nine constituents,after which the content determination was made.RESULTS Ten constituents showed good linear relationships within their own ranges(r≥0.999 7),whose average recoveries were 98.53%-102.22%with the RSDs of 1.26%-2.68%.The result obtained by QAMS approximated those obtained by external standard method.CONCLUSION This accurate and specific method can be used for the quality control of Tianma Toufengling Capsules.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Non-alcoholic fatty liver disease(NAFLD)is a kind of disease caused by a variety of reasons,which is characterized by steatosis and fat accumulation in liver parenchymal cells.In recent years,the morbidity of NAFLD has been relatively high in China.In the field of traditional Chinese medicine,NAFLD can be classified into the categories of"hepatic mass","abdominal mass"and"concretions and conglomerations".Spleen failing in transportation is the core pathogenesis of NAFLD,and the intervention of NAFLD with the method of activating spleen and resolving accumulation(shortened to Yunpi Huaji method)has achieved good results.In this paper,the clinical research of Yunpi Huaji method for the treatment of NAFLD and experimental research on its therapeutic mechanism in the past 10 years were reviewed.The results showed that the treatment of NAFLD by Yunpi Huaji method can be achieved by oral use of compound preparations and external treatment such as acupuncture,tuina and physiotherapy,and the therapeutic mechanism in the prevention and treatment of NAFLD was through multi-action,multi-target and multiple signaling pathways.The review will provide thoughts for the clinical diagnosis and treatment of NAFLD in traditional Chinese medicine,and will supply theoretical support for the medicine development and mechanism exploration of Yunpi Huaji method for the prevention and treatment of NAFLD.

Objective:To explore the clinical application and effect of FilmArray ? meningitis/encephalitis (ME) panel in identifying pathogens of central nervous system (CNS) infections in children. Methods:Molecular biology study.Cerebrospinal fluid (CSF) samples were prospectively obtained through lumbar puncture from children with suspected CNS infections admitted to the Department of Infectious Diseases at Beijing Children′s Hospital, Capital Medical University from May to November 2019.These samples were subjected to both routine clinical pathogen testing and FilmArray ME panel testing.Polymerase chain reaction was used to validate all samples.Independent sample t-test or Mann-Whitney U-test was used for comparative analysis of the results and influence factors obtained by the two detection methods. Results:A total of 113 cases of suspected CNS infections were enrolled.Routine clinical testing yielded 17 cases, with a positive rate of 15.0%, including 4 positive CSF cultures, with a positivity rate of 3.5%.FilmArray ME panel detected 23 positive cases, with a positive rate of 20.4%.FilmArray ME panel detected bacteria in 7 cases, viruses in 13 cases, fungi in 1 case, and both viruses and bacteria in 2 cases.Among the common pathogens detected, FilmArray ME panel obtained the results on average 2.7 days in advance.Conclusions:Compared with CSF culture, FilmArray ME panel has the advantages of shorter detection period, higher positive detection rate, and higher virus detection rate.

Objective To investigate the biomechanical effects of the backside design of tibial trays on the bone-prosthesis fixation interfaces in unicompartmental knee arthroplasty(UKA).Methods Finite element models of medial knee arthroplasty were constructed using a fixed UKA prosthesis.The knee joint load and joint motion under walking motion were considered as boundary conditions,and the differences in tibial von Mises stress,contact stress,and micromotion of the bone-prosthesis fixation interface of the UKA tibial trays with big keel,small keel,two-peg with fin,three-oblique peg,and three-upright peg types were compared.Results At the maximum medical knee force moment,compared to the two-peg with fin type,the tibial von Mises stress,contact stress,and micromotion of the bone-prosthesis fixation interface decreased by 8%and 15.9%and increased by 9.9%for the big keel type;decreased by 12.3%and increased by 7.5%and 0.9%for the small keel type;decreased by 10%,10.5%,and increased by 1.2%for the three-oblique peg type;and decreased by 7.7%,14.7%,and 1.6%for the three-upright peg type,respectively.However,the maximum micromotion of the bone-prosthesis fixation interface occurred at 21%of the gait cycle.Compared to the two-peg with fin type,the micromotion of the bone-prosthesis fixation interface increased by 11.6%for the big keel type,increased by 1.6%for the small keel type,decreased by 0.4%for the three-oblique peg type,and decreased by 2.3%for the three-upright peg type.Conclusions To improve the long-term fixation effects of tibial prostheses,it is recommended to focus on a two-upright peg with fin or small keel designs when UKA tibial trays are designed,which can effectively balance the stress transfer and interface micromotion,thereby ensuring prosthesis stability and reducing the risk of aseptic loosening.

OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.