Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

ObjectiveThe purpose of this study was to explore the difference in expression of gene between the osteosarcoma metastasis and primary specimens through NGS detection， in order to find the molecular mechanism of inducing osteosarcoma occurrence and metastasis. MethodsNext generation sequencing （NGS） was used to detect the tumor tissue samples of paired primary and metastatic lesions in 12 patients with metastasis， including 9 pairs of Panel detection （678 genes） and 3 pairs of whole exon detection （WES）. Copy number variation was detected by Excavator. DNA mutations were detected by Lumpy fusion， and RNA mutations were detected with Defuse + Star fusion. The distribution of mutations was shown by Circos. Metascape was used to analyze the enrichment of Go and KEGG signal pathways of differential genes. Pyclone+Citup/LICHEE was used for clonal evolution analysis. ResultsThe most frequent gene mutation mode of osteosarcoma was gene amplification， high-frequency mutation genes were FLCN（37.5%），GID4（37.5%），TP53（33.3%），ATRX（25%），CALR（25%），CCND3（25%），CCNE1（25%），NOCR1（25%），TFEB（25%），VEGFA（25%）， and the mutation frequency of cell cycle pathway was the highest. KT1， PLCG2 and EGFR were closely related to the metastasis of osteosarcoma. The frequency of tumor mutation burden （TMB） in metastatic lesions was significantly higher than primary lesions （P = 0.013）. Three patients detected by WES showed linear clonal evolution， suggesting that the mutations of osteosarcoma metastasis genes may be accumulated sequentially. We identified new candidate genes that may play an important role in the progression of osteosarcoma， including PLCG2， MYO15A and PEX6. ConclusionsThe most frequent gene mutation pattern of osteosarcoma occurrence and metastasis is gene amplification， and the frequency of tumor mutation burden （TMB） in metastatic lesions is significantly higher than that in primary lesions. There is an interrelated linear gene clonal evolution in patients with metastasis. This study suggests that PLCG2， MYO15A and PEX6 may play an important role in the progression of osteosarcoma.

ObjectiveTo explore the pharmacodynamic ingredients of Zhenqi Fuzheng granules （ZFG） for immunomodulatory through spectrum-effect relationship analysis， which provides experimental basis for improving the quality standard of ZFG. MethodEighteen batches of ZFG from six manufacturers were collected for analysis. The fingerprints were established by high performance liquid chromatography （HPLC）. Acetonitrile （A）-0.1% formic acid aqueous solution （B） were adopted as the mobile phase with gradient elution （0-15 min， 5%A； 15-23 min， 5%-8%A； 23-30 min， 8%-11%A； 30-45 min， 11%-18%A； 45-60 min， 18%-21%A； 60-67 min， 21%-23%A； 67-90 min， 23%-37%A）， the detection wavelength was 220 nm. Chemometric analysis such as similarity analysis and hierarchical cluster analysis （HCA） were subsequently used to analyze the similarities and chemical differences among these samples. A cyclophosphamide-induced immunodeficiency mouse model was used to evaluate the immune-enhancing effects of the products from different manufacturers. The spectrum-effect relationship between HPLC fingerprints and the immunomodulatory effects was examined using Spearman bivariate correlation analysis. HPLC coupled with mass spectrometry （HPLC-MSⁿ） was used to identify the spectrum-effect related peaks with electrospray ionization， positive and negative ion modes， and scanning range of m/z 100-1 500. ResultThe HPLC fingerprint of ZFG was established， and twenty peaks with good resolution were selected as common peaks. The results of quality analysis and pharmacodynamic test showed there were significant differences in both ingredients content and immune-enhancing effects of ZFG from different manufacturers. Through spectrum-effect relationship study， twelve peaks were screened as bioactive ingredients peaks. Thereafter， eight peaks among them were subsequently identified by HPLC-MSⁿ. They were salidroside （peak 2）， echinacoside （peak 5）， calycosin-7-glucoside （peak 6）， isomer of specnuezhenide （peak 7）， isonuezhenide （peak 9）， calycosin （peak 11）， nuezhenide G₁₃ or oleonuezhenide （peak 14）， and formononetin （peak 18）， respectively. ConclusionThere are differences in quality and efficacy of ZFG produced by different manufacturers. Through spectrum-effect relationship analysis， the medicinal ingredients of ZFG for immune-enhancing effects are screened， which can provide reference for the improvement of its quality standard.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

Many studies have shown that microRNAs (miRNAs) play vital roles during the spermatogenesis. However, little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia (NOA). Using microarray technology, the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined. Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs. The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which were then validated with a larger sample size. Correlations between the miRNA expression levels and clinical characteristics were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia. Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups. Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis, cell cycle, and mitotic prometaphase. In the subsequent qRT-PCR assays, the selected miRNA expression levels were consistent with the microarray results, and similar validated results were obtained with a larger sample size. Some clinical characteristics were significantly associated with the expression of certain miRNAs. In particular, we identified a combination of two miRNAs (miR-10b-3p and miR-34b-5p) that could serve as a predictive biomarker of azoospermia. This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis. These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.
Adult ; Azoospermia/genetics* ; Biopsy ; Cluster Analysis ; Computational Biology ; Follicle Stimulating Hormone/metabolism* ; Gene Expression Profiling ; Humans ; Luteinizing Hormone/metabolism* ; Male ; MicroRNAs/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction ; Spermatogenesis/genetics* ; Testis/metabolism* ; Testosterone/metabolism* ; Tissue Array Analysis

Objective To investigate the application value of enhanced recovery after surgery with no gastrointestinal decompression tube and with early postoperative oral feeding in minimally invasive radical resectionof esophageal cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 126 patients who underwent minimally invasive McKeown surgery in the General Hospital of Southern Theatre Command of PLA between March 2016 and October 2017 were collected.There were 80 males and 46 females,aged from 52 to 82 years,with an average age of 64 years.Of 126 patients,82 undergoing "li's anastomosis" with no gastrointestinal decompression tube and receiving early postoperative oral feeding were allocated into non-tube no fasting group,and 44 undergoing end-to-side gastroesophageal anastomosis with tubular stapler,conventionally indwelling gastrointestinal decompression tube,and beginning oral feeding at 1 week after surgery were allocated into traditional treatment group.Observation indicators:(1) surgical and postoperative recovery situations;(2) results of pathological examination;(3) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect the postoperative tumor recurrence and metastasis up to October 2018.Measurement data with normal distribution were represented as Mean ± SD,and comparison between groups was analyzed using independent sample t test.Measurement data with skewed distribution were expressed as M (range),and comparison between groups was analyzed by rank sum test.Count data were described as absolute number or percentage,and comparison between groups was analyzed using chi-square test.Ordinal data were analyzed by rank sum test.Results (1) Surgical and postoperative recovery situations:patients in the two groups underwent minimally invasive McKeown surgery successfully.Operation time,volume of intraoperative blood loss,incidence of anastomotic fistula,incidence of pulmonary complications,and duration of postoperative hospital stay were respectively (326±41) minutes,(225±96) ml,7.3 ％ (6/82),24.4％ (20/82),and 10 days (range,6-90 days) in the non-tube no fasting group and (317± 37) minutes,(214 ± 66) mL,9.1％ (4/44),20.5％ (9/44),and 14 days (range,10-42 days) in the traditional treatment group;there was a statistically significant difference in duration of postoperative hospital stay between the two groups (Z =-7.129,P ＜ 0.05) and no statistically significant difference in operation time,volume of intraoperative blood loss,incidence of anastomotic fistula,and incidence of pulmonary complications between the two groups (t =1.311,0.703,x2 =0.000,0.077,P＞0.05).(2) Results of pathological examination:the number of lymph node dissected,cases in postoperative TNM stage Ⅰ,Ⅱ and Ⅲ were respectively 27±5,12,55,15 in the non-tube no fasting group and 26±5,9,28,7 in the traditional treatment group,with no statistically significant difference between the two groups (t =0.549,Z =-0.747,P＞0.05).(3) Follow-up:of 126 patients,116 were followed up for 12-31 months,with a median time of 20 months,including 76 in the non-tube no fasting group and 40 in the traditional treatment group.During the follow-up,no tumor recurrence or metastasis was found in the 116 patients.Conclusion The enhanced recovery after surgery with no gastrointestinal decompression tube and with early postoperative oral feeding is safe and feasible in the McKeown surgery,which can significantly shorten the postoperative hospitalization time compared with the traditional treatment.

BACKGROUND: Increasing evidence has shown that visit-to-visit variability (VVV) of blood pressure (BP) is associated with an increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the impact of VVV of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the risk of CVD among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: We conducted a retrospective cohort study of 10,163 T2DM patients who were not previously diagnosed with CVD from January 2008 to December 2012 in Ningbo, China. The VVV of BP was calculated using five metrics, including standard deviation (SD), coefficient of variation (CV), variation independent of mean, average real variability, and successive variability (SV) of measurements, obtained over a 24-month measurement period. Hazard ratios and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression models for the associations of variability in BP with risk of CVD. RESULTS: A total of 894 CVD events were observed during a median follow-up of 49.5 months. The hazard ratio in the highest quintile of SD of SBP was 1.24 (95% CI, 1.01 to 1.52) compared with patients in the lowest quintile. The association between higher VVV of DBP and risk of CVD was not consistent across different metrics and sensitivity analyses. CONCLUSION: Higher VVV of SBP was associated with an increased risk of CVD, irrespective of the mean SBP level. Future studies are needed to confirm these findings.
Blood Pressure ; Cardiovascular Diseases ; China ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Follow-Up Studies ; Humans ; Retrospective Studies

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.
Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Pelvic Inflammatory Disease/drug therapy* ; Suppositories

OBJECTIVE: To summarizes the intratesticular condition of azoospermia patients, to understand azoospermia more intuitively, and improve the ability of clinical doctors to predict the success rate of microsperm extraction in azoospermia patients. METHODS: Azoospermia patients (excluding Klinefelter's syndrome) who underwent a micro-TESE during January 2014 and January 2018 in a single center were enrolled. The types of seminiferous tubules were summarized, and the clinical characteristics of different types of seminiferous tubules compared with the success rates of sperm extraction. In this study, 472 cases of non-obstructive azoospermia (excluding Klinefelter's syndrome) were analyzed by SPSS 21.0 software package. Relevant data were expressed by median(minimum,maximum).t-test was used to compare the difference of success rate of sperm extraction between each group and the group with the lowest rate (a type). RESULTS: The 472 patients with non-obstructive azoospermia underwent micro-TESE. The mean age of the patients was 31 (23, 46) years, the mean testicular size was 10 (1, 20) mL, the mean FSH was 15.4 (1.21, 68.4) IU/L, the mean T was 8.34 (0.69, 30.2) nmol/L, and totally 202 patients achieved success in micro-TESE (42.7%, 202/472). According to the seminiferous tubules seen during the operation, they were divided into the following six types: Class a, seminiferous tubules developed well and uniformly; Class b, seminiferous tubules developed well, occasionally slightly thick; Class c, seminiferous tubules were generally thin; Class d, seminiferous tubules basically atrophied, occasionally well-developed seminiferous tubules; Class e, all seminiferous tubules atrophied; Class f, seminiferous tubules were infiltrated by yellow substances. The success rate of micro-TESE varied greatly among different types of the patients. A total of 78 patients with type a were 29 (24, 40) years old, FSH 11.1 (1.21, 15.8) IU/L, T 10.2 (3.29, 26.5) nmol/L), and testicular size 12 (12, 20) mL. The successful rate of sperm extraction was 6.41%; 82 patients with type b were 31 (23, 42) years old, FSH 13.8 (3.23, 19.6) IU/L, T 9.44 (3.58, 30.2) nmol/L), and testicular size 12(8,15) mL. The successful rate of sperm extraction was 74.39%; There were 162 patients in group c, aged 31 (25, 40), FSH 19.6 (9.28, 26.6) IU/L, T 8.75 (5.66, 18.6) nmol/L, and testicular size 8 (5, 12) mL. The successful rate of sperm extraction was 45.06%. There were 36 patients in group d, aged 25 (23,38) years and FSH 28.5 (19.3, 45.6) IU/L, T 6.52 (2.12, 9.83) nmol/L, and testicular size 5 (3, 8) mL, and the success rate of sperm extraction was 94.44%. 26 patients with type e were 28(23, 46) years old, FSH 31.3 (18.5, 68.4) IU/L, T 6.72 (0.69, 18.2) nmol/L, and testicular size 5 (1, 8) mL. The success rate of sperm extraction was 45.38%. 88 patients with type f were 29 (24, 38) years old, FSH 18.5 (5.23, 31.6) IU / L, T 8.32 (3.58, 16.5) nmol/L, and testicular size 12 (6, 20) mL. The success rate of sperm extraction was 28.41%. CONCLUSION The success rate of micro-TESE in different types of seminiferous tubules in testis can be helpful to the judgement of the surgeon during the operation.
Adult ; Azoospermia ; Dissection ; Humans ; Male ; Middle Aged ; Sperm Retrieval ; Spermatozoa ; Testis ; Young Adult

Objective: To understand the distribution and treatment of malaria patients, and the characteristics of sampled hospitals in thephase of eradication of malaria,and provide support for medical resources allocation in the later stages of malaria eradication phase. On this basis, this study aims at promoting the realization of the ultimate goal of total eradication of malaria in China by 2020. Methods : A multi-stage stratified cluster sampling method was used. A total number of 102 hospitals in Zhejiang, Jiangsu, Anhui, Henan, Sichuan and Yunnan Provinces were selected to collect original information on in-patient and out-patient of malaria in terms of medical records and treatment costs during the periodfrom January 1st 2014 toDecember 31th2016. In order to conduct accurate statistical analysis, Excel 2016, SPSS 20. 0 and other Software were used. Results: The survey results collected a total number of 1633 malaria patients, and these patients showed a W-shaped distribution during the months of treatment. Most of malaria patients from Henan and Sichuan Provinceswere diagnosed as having been affected by falciparum and vivax malaria, and their number sharply increased. This is paper also revealed the ratios of malaria patientsin terms of their choice of health services,namely from tertiary hospitals, municipal medical institutions and provincial medical institutions; those were77.10％,52.05％ and 23.58％,respectively. Conclusions : A new period of peak incidence of malariais detected from 2014 to 2016. With hospitals' line of malaria defending ability shrinking,it was found that malaria treatment capacitiesare relatively concentrated in the high level hospitals,which plays a greater role when it comes to the prevention and control of malaria. It is recommended that regional malaria treatment lines should be built,and severe malaria treatment knowledge trainingsshould be prepared and attended in mass in orderto improve malaria treatment capacities.