OBJECTIVES: To study genotype-phenotype correlations in children with FGFR3 variants and to improve clinical recognition of related disorders. METHODS: Clinical data of 95 patients aged 0-18 years harboring FGFR3 variants, confirmed by whole‑exome sequencing at Shanghai Children's Medical Center from January 2012 to December 2023, were retrospectively reviewed. Detailed phenotypic characterization was performed for 22 patients with achondroplasia (ACH) and 10 with hypochondroplasia (HCH). RESULTS: Among the 95 patients, 52 (55%) had ACH, 24 (25%) had HCH, 9 (9%) had thanatophoric dysplasia, 3 (3%) had syndromic skeletal dysplasia, 2 (2%) had severe achondroplasia with developmental delay and acanthosis nigricans, and 5 (5%) remained unclassified. A previously unreported FGFR3 variant, c.1663G>T, was identified. All 22 ACH patients presented with disproportionate short stature accompanied by limb dysplasia, commonly with macrocephaly, a depressed nasal bridge, bowed legs, and frontal bossing; complications were present in 17 (77%). The 10 HCH patients predominantly exhibited disproportionate short stature with limb dysplasia and depressed nasal bridge. CONCLUSIONS ACH is the most frequent phenotype associated with FGFR3 variants, and missense variants constitute the predominant variant type. The degree of FGFR3 activation appears to correlate with the clinical severity of skeletal dysplasia.
Humans ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Child ; Male ; Child, Preschool ; Female ; Infant ; Adolescent ; Dwarfism/genetics* ; Achondroplasia/genetics* ; Lordosis/genetics* ; Infant, Newborn ; Retrospective Studies ; Genetic Association Studies ; Bone and Bones/abnormalities* ; Phenotype ; Limb Deformities, Congenital

Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

Objective To use superparamagnetic iron oxide nanoparticles(SPIONs)to label chimeric antigen receptor(CAR)T cells targeting carcinoembryonic antigen(CEA),and perform magnetic resonance imaging(MRI)to real time trace CEA CAR-T cells in vivo.Methods Appropriate amount of ferumoxytol,heparin sodium and protamine sulfate were mixed at high(ferumoxytol 100 μg/mL,heparin sodium 4 IU/mL,protamine sulfate 120 μg/mL),medium(ferumoxytol 50 μg/mL,heparin sodium 2 IU/mL,protamine sulfate 60 μg/mL),and low(ferumoxytol 25 μg/mL,heparin sodium 1 IU/mL,protamine sulfate 30 μg/mL)concentrations to form a SPIONs complex ferumoxytol/heparin/protamine(FHP),and then co-incubated with CEA CAR-T cells for cell labeling.The biocompatibility of FHP was detected by CCK-8 assay,EdU assay and flow cytometry.The uptake of FHP was detected by Prussian blue staining,and SPIONs content in the cells was quantitatively detected by inductively coupled plasma-mass spectrometry(ICP-MS).Flow cytometry was used to detect the lytic effect of FHP-labeled CEA CAR-T cells on tumor cells,and MRI was employed to scan FHP-labeled CEA CAR-T cells.Results FHP at high,medium,and low concentrations had no significant effect on the activity of CEA CAR-T cells,with cell activity above 100％determined by CCK-8 assay.DNA proliferation was above 94.3％in EdU assays.Prussian blue staining showed that CEA CAR-T cells could take FHP up,with the uptake increased with the increment of FHP concentration.ICP-MS showed that the intracellular Fe content was 440.23±189.36 ng/mL.Tumor cell killing experiment showed that FHP-labeled CEA CAR-T cells had excellent killing capability against tumor cells.MRI scans indicated that T2WI signals of FHP-labeled CEA CAR-T cells were significantly reduced with increasing FHP concentration(P＜0.01).Conclusion SPIONs complex FHP shows good biocompatibility and can effectively label CEA CAR-T cells.SPIONs complex FHP can be used as a magnetic marker for CEA CAR-T cells and a feasible MRI tracer for clinical application.

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.

OBJECTIVE: To explore the relationship between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and the risk of acute ischemic stroke (AIS) recurrence in hypertensive patients. METHODS: This retrospective case-control study was conducted among 211 hypertensive patients with AIS treated in Foshan First People's Hospital, including 35 patients with recurrence of AIS during the 1-year follow-up as confirmed by head CT/MR. In the overall patients, 60 had grade 1 hypertension (including 5 recurrent cases), 76 had grade 2 hypertension (with 11 recurrent cases), and 75 had grade 3 hypertension (with 19 recurrent cases). Univariate analysis, multivariate logistic regression analysis, trend analysis, and smooth curve fitting analysis were performed to explore the correlation between serum Lp-PLA2 level within 24 h after admission and the risk of AIS recurrence. The predictive efficacy of serum Lp-PLA2 level for AIS recurrence in different hypertension grades was evaluated using ROC curve analysis. RESULTS: Serum Lp-PLA2 level, age, NIHSS score at admission, mRS scores at 7 days, homocysteine level and smoking status differed significantly between patients with and without AIS recurrence (P < 0.05). After adjustment for confounding factors, multivariate regression analysis showed that the highest tertile of Lp-PLA2 level was associated with a 4.13-fold increase of AIS recurrence risk compared with the lowest tertile (OR=5.13, 95% CI: 1.35-19.40), and each 1 ng/mL increase of Lp-PLA2 level was associated with a 1% increase of AIS recurrence risk (OR= 1.01, 95% CI: 1.01-1.02). Serum Lp-PLA2 level was shown to positively correlate with AIS recurrence risk, and in patients with grade 3 hypertension, its areas under the ROC curve for predicting AIS recurrence was 0.869 with a specificity of 0.893 and a sensitivity of 0.737. CONCLUSION Serum Lp-PLA2 concentration is an independent risk factor and potentially an effective predictor for AIS recurrence in patients with grade 3 hypertension.
Humans ; Infant, Newborn ; 1-Alkyl-2-acetylglycerophosphocholine Esterase ; Acute Disease ; Biomarkers ; Brain Ischemia/etiology* ; Case-Control Studies ; Cerebral Infarction ; Hypertension/complications* ; Ischemic Stroke/complications* ; Retrospective Studies ; Risk Factors ; Stroke

OBJECTIVE: To observe the clinical effect and safety of acupuncture in treatment of neck pain due to cervical spondylosis. METHODS: According to the patients' preference and acceptance for the interventions of neck pain induced by cervical spondylosis, an acupuncture group (221 cases) and a non-acupuncture group (251 cases) were divided. After the control of confounding factors with propensity score matching, 218 cases were included in either acupuncture group or non-acupuncture group. In the acupuncture group, acupuncture was applied to Dazhui (GV 14), Baihui (GV 20), ashi points, bilateral neck-Jiaji (EX-B 2), Fengchi (GB 20), Houxi (SI 3), Shenmai (BL 62), etc. The treatment was given once daily, one course of intervention was composed of 5 treatments and 3 courses were included. In the non-acupuncture group, the oral administration of imrecoxib tablets and cobalt tablets was prescribed for 2 weeks. Before and after treatment, the scores of Northwick Park questionnaire (NPQ) and the simplified McGill pain questionnaire (SF-MPQ) were observed, and the safety was assessed in patients of the two groups. RESULTS: After treatment completion, the scores of NPQ and SF-MPQ were all reduced when compared with those before treatment in each group (P<0.001), and the scores of NPQ and SF-MPQ in the acupuncture group were lower than those of the non-acupuncture group (P<0.001). The incidence of adverse reactions was 6.0% (13/218) in the acupuncture group and was 10.1% (22/218) in the non-acupuncture group, without statistical significance in comparison (P>0.05). CONCLUSION Acupuncture is effective and safe in the relief of neck pain and the improvement of comprehensive quality of life in the patients with cervical spondylosis.
Humans ; Neck Pain/therapy* ; Propensity Score ; Quality of Life ; Acupuncture Points ; Acupuncture Therapy ; Spondylosis/therapy* ; Treatment Outcome

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSV_MT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSV_MT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSV_ΔGMT-S_Δ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding S_Δ21 of Delta-variant can induce more potent immune responses compared with those encoding S_Δ21 of Omicron- or WA1-strain. VSV_MT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.