Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To observe the effect of omeprazole enteric-coated capsules on clinical symptoms and serum inflammatory factor levels in children with chronic gastritis and peptic ulcer.Methods Children with chronic gastritis and peptic ulcer were divided into treatment group and control group by random number table method.The control group was given triple therapy of ranitidine hydrochloride tablets,amoxicillin and clarithromycin,while the treatment group was treated with omeprazole enteric-coated capsules combined with amoxicillin and clarithromycin.Clinical efficacy,symptom relief time,and changes in serum motilin(MOT),gastrin(GAS)and inflammatory factors[interlrukin-6(IL-6)and interlrukin-8(IL-8)]were compared between the two groups.Results There were 48 cases in treatment group and 48 cases in control group.After treatment,the total effective rates in treatment group and control group were 93.74％(45 cases/48 cases)and 85.42％(41 cases/48 cases),with significant difference(P＜0.05).After treatment,the disappearance time of ulcer induced pain in treatment group and control group were(1.51±0.26)and(2.08±0.42)d;the disappearance time of acid regurgitation were(2.29±0.40)and(2.93±0.33)d;the disappearance time of burning sensation were(2.37±0.21)and(2.85±0.54)d;the length of hospital stay were(6.21±1.07)and(6.94±1.25)d;serum MOT levels were(298.48±35.15)and(273.58±31.25)pg·mL-1;serum GAS levels were(167.28±19.46)and(128.32±18.61)ng·L-1;IL-6 levels were(58.67±5.39)and(76.14±6.63)mg·mL-1;IL-8 levels were(50.08±5.16)and(58.68±5.49)mg·mL-1.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 8.33％and 12.50％,with no statistical significance(P＞0.05).Conclusion Omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer can effectively alleviate various clinical symptoms and improve clinical efficacy.At the same time,it can lower serum levels of inflammatory factors and improve inflammation,with good effect.

AIM To explore the clinical effects of Bushen Huoxue Ointment Formula on patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern.METHODS One hundred and sixty-seven patients were randomly assigned into control group(55 cases)for 2-year intervention of conventional treatment,exposure group(54 cases)for 2-year intervention of both Bushen Huoxue Decoction and conventional treatment,and high exposure group(58 cases)for 2-year intervention of Bushen Huoxue Ointment Formula,Bushen Huoxue Decoction and conventional treatment.The changes in clinical effects,BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,ASQoL score,SPARCC score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23,IL-35,NLR,PLR and safety indices were detected.RESULTS The high exposure group demonstrated more ASAS40,ASASAS5/6,BASDAI50 cases than the exposure group and the control group(P<0.05).After the treatment,the high exposure group displayed lower BASDAI score,ASDAS-CRP,BASFI score,spinal pain score,PGA score,BASMI score,SPARCC score,ASQoL score,Kidney Deficiency and Blood Stasis Pattern score,ESR,CRP,IL-6,TNF-α,IL-17,IL-23 than the other two groups(P<0.05),and higher IL-35(P<0.05).After adjusting confounding factors by logistic regression analysis,Bushen Huoxue Decoction and Bushen Huoxue Ointment Formula reduced BASDAI score,ASDAS-CRP(P<0.05),and enhanced clinical effects(P<0.05).No serious adverse reactions were found in the three groups.CONCLUSION For the patients with ankylosing spondylitis of Kidney Deficiency and Blood Stasis Pattern,Bushen Huoxue Ointment Formula can safely and effectively inhibit inflammation,reduce disease activity,alleviate bone marrow edema,improve clinical symptoms,and enhance joint functions and life quality.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective:To explore if miR-133a is involved in the occurrence and development of hepatocellular carcinoma(HCC)via regulating G6PD.Methods:Bioinformatics analysis predicted the binding sites of miR-133a and G6PD;RT-PCR or western blot was used to assess the expres-sion of miR-133a and G6PD in HCC tissues and the adjacent normal tissues;CCK-8 and flow cy-tometry assays were performed to evaluate the effects of miR-133a/G6PD on cell proliferation,apop-tosis;Fluorescent reporter gene and western blot assays were used to assess the effect of miR-133a on G6PD expression.Results:miR-133a expression was decreased in HCC tissues while G6PD was increased(P0.01);Up-regulation of miR-133a significantly reduced G6PD expression(P＜0.01);up-reg-ulation of miR-133a inhibited cell growth and promoted cell apoptosis(P＜0.05),whereas these effects induced by miR-133a over-expression were all abolished when G6PD was up-regulated(P＜0.01).Conclusion:miR-133a represses the occurrence and development of HCC via targeting G6PD.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective To standardize the management of clinical trials in our hospital,reduce the incidence of protocol deviations,and provide a reference for improving the quality of clinical trials.Methods The healthcare failure mode and effect analysis(HFMEA)method was used to determine the potential failure modes of the current protocol deviation.The frequency,severity and detectability of failure modes were quantified and evaluated.The risk priority number(RPN)was calculated and the corresponding improvement measures were proposed.The RPN values before and after the implementation of HFMEA were statistically analyzed to evaluate the improvement effect.Results After the implementation of HFMEA activities,the RPN values of 14 potential failure modes decreased significantly(P<0.05);The risk level of 12 potential failure modes decreased.The HFMEA team members'ability in finding and solving problems,communication and cooperation were significantly improved.Conclusions The implementation of HFMEA activities contributes to the management of protocol deviation in clinical trials,can effectively reduce the occurrence of protocol deviation,and provides experience for improving the quality of drug clinical trials.

Objective To explore early diagnostic biological markers for Leigh syndrome caused by the m.8993T>G mutation.Methods A retrospective analysis was performed on the clinical data of four children diagnosed with m.8993T>G mutation-related mitochondrial disease at the Children's Hospital of Chongqing Medical University from January 2014 to January 2024.Additionally,a literature review was conducted.Results All four children had plasma amino acid and acylcarnitine analyses that revealed decreased citrulline levels,and one child was initially identified through neonatal genetic metabolic disease screening.According to the literature review,there were 26 children with mitochondrial disease and hypocitrullinemia caused by the m.8993T>G mutation(including the four children in this study).Among these,12 children exhibited clinical phenotypes of Leigh syndrome or Leigh-like syndrome,while 18 children were identified with hypocitrullinemia and/or elevated levels of 3-hydroxyisovalerylcarnitine(C5-OH)during neonatal genetic metabolic disease screening.Conclusions Hypocitrullinemia may serve as a potential biomarker for the early diagnosis of m.8993T>G mutation-associated Leigh syndrome,detectable as early as during neonatal genetic metabolic disease screening.

Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2％,100％,58.3％,88.9％,respectively,which were better than 44.4％,83.3％,33.3％,66.7％in control group(P＜0.05).There was no statistical significance in planning of femoral head prosthesis size(P＞0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P＜0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P＞0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P＜0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P＞0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P＜0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.