Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

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.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

China ; History of Medicine ; Medicine/standards*

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective: To analyze correlation of occupational hydrogen fluoride exposure to low doses of bone metabolism index through occupational epidemiological investigation and benchmark dose calculation. Methods: In May 2021, using cluster sampling method, 237 workers exposed to hydrogen fluoride in a company were selected as the contact group, and 83 workers not exposed to hydrogen fluoride in an electronics production company were selected as the control group. The external exposure dose and urinary fluoride concentration, blood and urine biochemical indicators of the workers was measured.The relationship between external dose and internal dose of hydrogen fluoride was analyzed. The external dose, urinary fluoride was used as exposure biomarkers, while serum osteocalcin (BGP), serum alkaline phosphatase (AKP) and urinary hydroxyproline (HYP) were used as effect biomarkers for bone metabolism of hydrogen fluoride exposure. The benchmark dose calculation software (BMDS1.3.2) was used to calculate benchmark dose (BMD) . Results: Urine fluoride concentration in the contact group was correlated with creatinine-adjusted urine fluoride concentration (r=0.69, P=0.001). There was no significant correlation between the external dose of hydrogen fluoride and urine fluoride in the contact group (r=0.03, P=0.132). The concentrations of urine fluoride in the contact group and the control group were (0.81±0.61) and (0.45±0.14) mg/L, respectively, and the difference between the two groups was statistically significant (t=5.01, P=0.025). Using BGP, AKP and HYP as effect indexes, the urinary BMDL-05 values were 1.28, 1.47 and 1.08 mg/L, respectively. Conclusion: Urinary fluoride can sensitively reflect the changes in the effect indexes of biochemical indexes of bone metabolism. BGP and HYP can be used as early sensitive effect indexes of occupational hydrogen fluoride exposure.
Humans ; Fluorides/adverse effects* ; Hydrofluoric Acid ; Benchmarking ; Biomarkers ; Occupational Exposure/adverse effects*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

G-quadruplexes with different conformations often exhibit different binding abilities to proteins and play different physiological functions. It is of great significance to analyze the factors affecting the configuration of G-quadruplex to explore its physiological function. Different from DNA, RNA sequences have shown parallel G-quadruplex structures in previous reports. However, we found that the only RNA sequence, the 22-nt telomere RNA fragment (ORN-N, A

Humans ; Otitis Media, Suppurative ; Chronic Disease ; Biofilms ; Otitis Media

Background: Cervical cancer is still present a major public health problem, especially in developing countries. In International Federation of Gynaecology and Obstetrics 2018, allowing assessment of retroperitoneal lymph nodes by imaging and/or pathological findings and, if deemed metastatic, the case is designated as stage IIIC (with r and p notations). Patients with lymph node metastases have lower overall survival (OS), progression free survival (PFS), and survival after recurrence, especially those who have unresectable macroscopical positive lymph nodes. Retrospective analysis suggests that there may be a benefit to debulking macroscopic nodes that would be otherwise difficult to sterilize with standard doses of radiation therapy. However, there are no prospective study reporting that resecting macroscopic nodes before concurrent chemoradiation therapy (CCRT) would improve PFS or OS of cervical cancer and no guidelines for surgical resection of bulky lymph nodes. The CQGOG0103 study is a prospective, multicenter and randomized controlled trial (RCT) evaluating lymph node dissection on stage IIICr of cervical cancer. Methods Eligible patients are histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, adeno-squamous cell carcinoma. Stage IIICr (confirmed by computed tomography [CT]/magnetic resonance imaging/positron emission tomography/CT) and the short diameter of image-positive lymph node ≥15 mm. 452 patients will be equally randomized to receive either CCRT (pelvic external-beam radiotherapy [EBRT]/extended-field EBRT + cisplatin [40 mg/m2] or carboplatin [the area under curve=2] every week for 5 cycles + brachytherapy) or open/minimally invasive pelvic and para-aortic lymph node dissection followed by CCRT. Randomization is stratified by status of para-aortic lymph node. The primary endpoint is PFS. Secondary endpoints are OS and surgical complications. A total of 452 patients will be enrolled from multiple hospitals in China within 4 years and followed up for 5 years.