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

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

Case 1: A 19-day-old male infant presented with poor feeding and decreased activity for 2 weeks, worsening with poor responsiveness for 3 days. At 5 days old, he developed poor feeding and poor responsiveness, was hospitalized, and was found to have elevated blood ammonia and thrombocytopenia. Whole-genome genetic analysis revealed a pathogenic homozygous mutation in the PCCA gene, NM-000282.4: c.1834-1835del (p.Arg612AspfsTer44), leading to a diagnosis of propionic acidemia. Case 2: A 4-day-old male infant presented with poor responsiveness and feeding difficulties since birth, with elevated blood ammonia for 1 day. He showed weak sucking and deteriorating responsiveness, with blood ammonia >200 µmol/L. Genetic testing identified two heterozygous mutations in the MMUT gene: NM_000255.4: c.1677-1G>A and NM_000255.4: ex.5del, confirming methylmalonic acidemia. Case 3: A 20-day-old male infant presented with poor feeding for 15 days and skin petechiae for 8 days. He developed feeding difficulties at 5 days old and lower limb petechiae at 12 days old, with blood ammonia measured at 551.6 µmol/L. Genetic analysis found two heterozygous mutations in the PCCA gene: NM_000282.4: c.1118T>A (p.Met373Lys) and NM_000282.4: ex.16-18del, confirming propionic acidemia. In the first two cases, continuous hemodiafiltration was performed for 30 hours and 20 hours, respectively, before administering carglumic acid. In the third case, carglumic acid was administered orally without continuous hemodiafiltration, resulting in a decrease in blood ammonia from 551.6 µmol/L to 72.0 µmol/L within 6 hours, with a reduction rate of approximately 20-25 µmol/(kg·h), similar to the first two cases. Carglumic acid was effective in all three cases, suggesting it may help optimize future treatment protocols for organic acidemia.
Humans ; Male ; Infant, Newborn ; Propionic Acidemia/drug therapy* ; Amino Acid Metabolism, Inborn Errors/genetics* ; Mutation ; Methylmalonyl-CoA Decarboxylase/genetics* ; Citrates/administration & dosage* ; Carbon-Carbon Ligases/genetics* ; Glutamates

OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China