Recent years have witnessed significant advances in the development of novel techniques and methodologies for identifying active ingredients in traditional Chinese medicine (TCM), substantially advancing research and development efforts. Spectrum-effect correlation analysis, affinity ultrafiltration, high-content screening (HCS) imaging, and cell membrane chromatography (CMC) have emerged as essential tools, effectively linking TCM chemical constituents to their biological effects, thereby enabling efficient active ingredient screening. Additionally, molecular interaction analysis provides deeper insights into TCM-biomolecule interaction mechanisms, enhancing understanding of its therapeutic potential. Computer-aided techniques facilitate TCM active ingredient identification, optimizing the screening process for efficiency and cost-effectiveness. Molecular probe technology, as an emerging methodology, enables precise and rapid screening for novel therapeutic drug discovery. Ongoing technological advancement in this field indicates promising future developments, potentially leading to more effective and targeted TCM-based therapies.
Drugs, Chinese Herbal/chemistry* ; Medicine, Chinese Traditional/methods* ; Humans ; Drug Discovery/methods* ; Animals

OBJECTIVE To synthesize bivalent γ-carboline derivatives and determine their acetylcholinesterase inhibition activity. METHODS The key intermediate γ-carboline was synthesized by Fischer method using N-acetyl- 3-bromo-4-piperidone and phenylhydrazine as starting materials. The γ-carboline synthesized was then reacted with ω,ω’- dibromoalkanes in the presence of NaH to form bivalent γ-carboline derivatives. Methylation of γ-carboline derivative with iodomethane in methanol yielded its quaternary ammonium salt. The acetylcholinesterase activity was measured by Ellman method with slight modification. RESULTS Seven novel carboline derivatives were synthesized and their structures were characterized by IR, 1H-NMR, 13C-NMR and ESI-MS. The results of pharmacological experiments indicated that all the target compounds showed inhibition activity against the acetylcholinesterase. Compound 4g exhibited inhibitory activity similar to that of the positive control donepezil. CONCLUSION Bivalent γ-carboline derivatives have inhibition activity against the acetylcholinesterase. The length of the connecting chain has an impact on the activity. It shows the best activity with chain length of eight carbon atoms, and the quaternization of tertiary nitrogen in the structure is beneficial for raising the inhibitory activity.

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Objective:To analyze the correlation between clinical phenotypes and genotypes in 6 children with primary distal renal tubular acidosis (dRTA).Methods:The clinical data of 6 children confirmed as dRTA in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from November 2017 to August 2019 were collected, and related auxiliary examination was performed to assess their growth and development.The venous whole blood was reserved for Trio whole exome sequencing, and full spectrum genetic disease accurate diagnosis cloud platform was applied to systematic data screening and analysis.The suspected mutations were checked by Sanger sequencing, and then the role of protein was predicted by software.Results:Clinical manifestations, signs and auxiliary examination results of the 6 children accorded with the diagnostic criteria of dRTA, and the prominent characteristics was growth retardation.One case had knee valgus, one had osteoporosis, and the auxiliary examination results showed that both of them had alkaline urine, metabolic acidosis, and hypokalemia.Three children had nephrocalcinosis, and 2 children had nephrolithiasis.The parents of the 6 patients were all normal without phenotypes.Mutations in the SLC4A1 gene were identified in 4 patients, including 1 child with a reported homozygous autosomal recessive missense mutation(c.2102G>A, p.G701D), who had dRTA and hemolytic anemia, and 3 children with the reported de novo heterozygous autosomal dominant missense mutation(c.1766G>A, p.R589H, c.1765C>T, p.R589C), whose age at diagnosis was related to abnormal renal imaging.Compound heterozygous autosomal recessive mutations in the ATPV1B1 gene were identified in 1 patient, and they were novel heterozygous missense mutations (1153C>A, p.P385T and c. 806C>T, p.P269L). A novel homozygous autosomal recessive missense mutation was identified in 1 patient in the ATPV0A4 gene(c.1899C>A, p.Y633X, 208). Conclusions:Mutations in SLC4A1, ATP6V1B1, ATP6V0A4 genes are identified as the main causes of the primary dRTA, and the phenotypes was related to the mutation features and genotypes.Genetic test should be conducted on patients suspected as dRTA for early molecular diagnosis, thereby improving clinical phenotypic screening and individualized treatment.

Objective To investigate the clinical manifestations and genetic features of children with papillorenal syndrome caused by PAX2 gene mutation.Methods Clinical manifestations,imaging changes and sequencing data were collected and analyzed from a family with papillorenal syndrome who were diagnosed in Wuhan Children's Hospital in February 2018."PAX2","papillorenal syndrome" and "renal coloboma syndrome" were used as key words to search in China National Knowledge Infrastructure,Wangfang Data Knowledge Service Platform,PubMed and Human Gene Mutation Database up to April 2018.Results A ten years old girl was admitted due to "edema and urine output decreased for one week".Lab showed BUN 25.30 mmol/L,Scr 766.5 μmol/L,Urine protein 3.6 g/24 h.Imaging examination showed bilateral vesical and ureter reflux combined with left duplex kidney and duplication of ureter.Developmental dysplasia of the left hip was also found.The father of the patient had been diagnosed with chronic kidney disease for 10 years and on hemodialysis for 6 years.Next generation sequencing revealed that both the father and daughter carried a heterozygous nonsense mutation in the exon3 c.219C ＞ G(p.Y73X) of PAX2.No Chinese literature ever was reported about papillorenal syndrome.Ninety-four articles in English were retrieved and 177 patients with papillorenal syndrome were confirmed by gene analysis with a total of 92 PAX2 variants.Ten nonsense mutations had been reported.Developmental dysplasia of the hip (DDH) never be reported before.Conclusion Papillorenal syndrome caused by PAX2 mutation can mainly manifest as abnormal development of both kidney and optic nerve,which may be accompanied by other systemic abnormalities,it is rarely reported in China.DDH may be a new phenotype of papillorenal syndrome.

Objective To analyze the early risk factors of overweight and obesity in preschool children.Methods Using stratified cluster sampling,the data of 1 335 preschool children's physical examination in High-tech Zone,Urumqi,Xinjiang were collected,and the case group had 153 overweight and obese children,the control group had 1 182 non-overweight and obese children;a case-control study was conducted.The basic data of mothers and the basic data of neonatal birth were analyzed retrospectively.The univariate and unconditional multivariate logistic regression analysis was performed.Results The prevalence of overweight and obesity in preschool children in High-tech Zone in Urumqi was 11.5％.Non-conditional multivariate logistic regression analysis showed that children's age (OR=1.31,95％ CI:1.07-1.61),mother's pre-pregnancy BMI (OR=1.11 95 ％,CI:1.06-1.17) and whether mothers had gestational hypertension (OR=1.99 95％,CI:1.03-3.85) were the risk factors for overweight and obesity in preschool children (P＜0.05).Conclusion In Urumqi high school district preschool children's overweight and obesity rate was high;mothers with high BMI before pregnancy,and those with high blood pressure during pregnancy can increase the risk of overweight and obesity in children,preschool children's increased age may increase the risk of overweight and obesity in children.

Objective To evaluate the short-term efficacy of total hip arthroplasty combined with subcutaneous osteotomy in the treatment of CroweⅣ hip dysplasia (DDH).Methods From March 2012 to March 2015,14 patients (16 hips) underwent total hip arthroplasty with femoral distraction osteotomy S-ROM femoral stem prosthesis.And we observed its recent efficacy.Results All patients underwent S-ROM prosthesis.The patients underwent transverse osteotomy of the femoral trochanter.The osteotomy length was 2.0-3.5 cm.The average follow-up time was 19 months.And no complications such as dislocation,vascular nerve injury,deep vein thrombosis and infection were observed during the follow-up.The average Harris scores improved from 42.3 preoperatively to 90.4 postoperatively at 9 months after the operation.The average lengths of preoperative limb shortening and postoperative limb shortening were 6.4 cm and 4.3 cm respectively.The X-ray films showed no dislocation of acetabulum and femoral prosthesis.Bone healing was achieved at 6 months after osteotomy.Conclusion This method could be a good choice for Crowe Ⅳ developmental dysplasia.The short-term efficacy is satisfactory.

Objective To investigate the clinical efficacy of combined use of calcineurin inhibitor in the treatment of lupus nephritis in induction or maintenance,which is resistant to mycophenolate mofetil.Methods Sixty-six cases of children with lupus nephritis were selected from February 2014 to September 2016 in Huazhong University of Science and Technology,Tongji Medical College Affiliated Wuhan Children's Hospital.The randomized method was used to divide them into the control group and the observation group randomly.Among them,31 cases in the control group were given glucocorticoid,cyclophosphamide combined with traditional medicine for treatment;35 cases in observation group were given glucocorticoid,mycophenolate mofetil,tacrolimus (calcine phosphatase inhibitor) multi-target therapy for treatment.The clinical effect of 2 groups before and after treatment were compared,and the incidence of adverse reactions in the treatment of 2 groups of children were compared.Results After treatment,the levels of systemic lupus erythematosus disease activity index (SLEDAI),serum creatinine and 24 h urine protein [(6.05 ± 1.04) scores,(45.08 ± 18.52) μmol/L,(0.96 ±0.30) g/L] in the observation group were lower than those in the control group [(11.09 ±2.33) scores,(95.33 ±36.74) μmol/L,(2.05 ±0.74) g/L],and the differences were statistically significant (t =3.097,3.356,3.871,all P ＜ 0.05).Serum complement C3,plasma albumin levels [(1.05 ± 0.28) g/L,(63.24 ± 12.98) g/L] were higher than those in the control group [(0.34 ±0.10) g/L,(35.45 ±6.74) g/L],and the differences were statistically significant (t =4.124,3.567,all P ＜ 0.05).After treatment,the levels of serum complement C3 and plasma albumin were significantly higher between 2 groups than those before treatment,the differences were statistically significant (all P ＜ 0.05).The incidence of adverse reaction (14.29％,5/35 cases) in the observation group was lower than that in the control group (38.71％,12/31 cases),and the difference was statistically significant (x2 =5.128,P ＜ 0.05).Conclusion Multi-target combination therapy and traditional cyclophosphamide therapy can effectively control lupus nephritis in children,but the clinical effect of multi-target combination therapy is better and the adverse reaction is less.

Objective To observe the effect of cinobufotalin freeze-dry powder on heart rate ( HR ) and electrocardiogram ( ECG) of SD rats and to provide experimental basis for monitoring its adverse effect on heart in clinical application. Methods The drug was administered into external jugular vein at constant speed throughout the whole experiment;standard-Ⅱ limb lead monitored the HR and ECG, and then the changes in HR and ECG before and after administration of cinobufotalin were compared. Results Thirty minutes after administration of cinobufotalin injection and cinobufotalin freeze-dry powder at middle dose and high dose, HR of the rats was significantly increased as compared with blank control group[(469±40) bpm, (466±29) bpm and (484±40) bpm vs. (411±17) bpm] (P<0. 05), but soon afterwards, it returned to normal. A small number of rats also developed arrhythmia. In addition, administration of cinobufotalin significantly shortened the P-R interval[blank control group: (46. 90±3. 90) ms, cinobufotalin injection administration group: (39. 70± 2. 54) ms;middle dose of cnobufotalin freeze-dry powder administration group: (37. 70±3. 77) ms; high dose of cinobufotalin freeze-dry powder administration group:(39. 30±7. 12) ms] and Q-T interval[blank control group:(61. 29±9. 46) ms;middle dose of cinobufotalin freeze-dry powder administration group: (55. 13±4. 67) ms; high dose of cinobufotalin freeze-dry powder administration group:(51.75±11. 53) ms] (P<0. 05), but QRS and S-T were unchanged (P>0. 05). Conclusion Cinobufotalin freeze-dry powder has some side effects on rat heart and can increase HR, even lead to arrhythmia.

Objective To study the efficacy of sequential blood purification treatment of bee poisoning complicated by multiple organ disfunction syndrome (MODS).Methods The 11 cases of children with bee poisoning and MODS from Wuhan Children's Hospital were treated with sequential blood purification therapy,and they were treated with plasma exchange (PE),hemoperfusion (HP) and sequential continuous renal replacement therapy (CRRT) simultaneously in the early stage,and then were treated with intermittent hemodialysis (IHD) in the remission stage.Different modes of purification treatment were applied in different stages.The trends of liver function,renal function and myocardial enzymes were observed in 11 cases before and after therapy,later a retrospective analysis was performed,and the efficacy of sequential blood purification was studied.Results Ten in 11 cases of children were treated with HP,CRRT and IHD therapy,and among them 6 cases were treated with PE on the first day of admission.One case,the youngest of children admitted to hospital less than 24 hours,died of sudden cardiac arrhythmia due to toxic myocarditis.In ten cases of the children after treatment,their myocardial enzymes returned to normal at first,and then jaundice and hepatic function improved,and renal function gradually improved after 10 days.Two weeks after discharge,through reviewing of the liver and kidney function,myocardial enzymes returned to normal indicators.In review of urine,5 cases were accompanied with microscopic hematuria,3 cases were accompanied with hematuria and proteinuria,and 2 cases were completely normal.The improved cure rate was 91％ (10/11 cases).Conclusions Sequential blood purification treatment is the main and effective means for severe bee poisoning complicated with MODS in children in the early stage.