Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

OBJECTIVES: To study the clinical features and fibroblast growth factor receptor 3 (FGFR3) gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases. METHODS: A retrospective analysis was performed on the clinical data and FGFR3 gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021. RESULTS: Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). The common imaging findings were rhizomelic shortening of the long bones (100%, 17/17) and narrowing of the lumbar intervertebral space (88%, 15/17). Major complications included skeletal dysplasia (100%, 17/17), middle ear dysfunction (82%, 14/17), motor/language developmental delay (88%, 15/17), chronic pain (59%, 10/17), sleep apnea (53%, 9/17), obesity (41%, 7/17), foramen magnum stenosis (35%, 6/17), and hydrocephalus (24%, 4/17). All 17 children (100%) had FGFR3 mutations, among whom 13 had c.1138G>A hotspot mutations of the FGFR3 gene, 2 had c.1138G>C mutations of the FGFR3 gene, and 2 had unreported mutations, with c.1252C>T mutations of the FGFR3 gene in one child and c.445+2_445+5delTAGG mutations of the FGFR3 gene in the other child. CONCLUSIONS This study identifies the unreported mutation sites of the FGFR3 gene, which extends the gene mutation spectrum of ACH. ACH is a progressive disease requiring lifelong management through multidisciplinary collaboration.
Achondroplasia/genetics* ; Child ; Humans ; Mutation ; Osteochondrodysplasias/genetics* ; Receptor, Fibroblast Growth Factor, Type 3/genetics* ; Retrospective Studies

ObjectiveTo evaluate the clinical curative effect of modified Shaofu Zhuyutang on pelvic pain of endometriosis （EMT） with syndrome of cold congeal and blood stasis and the influence on neural angiogenesis. MethodA total of 110 cases were divided into a control group （54 cases） and an observation group （56 cases） by the random number table method. Patients in the control group took Aifu Nuangong pills with 6 g/time and 2 times/day. Patients in the observation group took modified Shaofu Zhuyutang with 1 dose/day. Course of treatment continued for 3 menstrual cycles. Dysmenorrhea， other symptoms and signs of pelvic pain， and the EMT health profile-5 （EHP-5） for patients with syndrome of cold congeal and blood stasis and EMT were scored before and after treatment. The levels of peripheral blood nerve growth factor （NGF）， substance P （SP）， calcitonin gene-related peptide （CGRP）， brain-derived neurotrophic factor （BDNF）， soluble Fms-like tyrosine kinase（sFlt-1）， vascular endothelial growth factor （VEGF）， matrix metalloproteinase-9 （MMP-9）， and insulin growth factor-1 （IGF-1） were detected before and after treatment. The levels of prostaglandin E₂ （PGE₂）， cyclooxygenase-2 （COX-2）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and other inflammatory factors were detected before and after treatment. The pain medication usage and recurrence were recorded. ResultThe scores of dysmenorrhea， symptoms of pelvic pain symptoms （non-menstrual pelvic pain， dyspareunia， anal falling pain， and defecation pain， etc.）， and signs of pelvic pain （pelvic tenderness and sacral ligament tender nodules） in the observation group were lower than those in the control group （P<0.01）. The disappearance rates of dysmenorrhea， pelvic tenderness， and sacral ligament tender nodules were 67.35% （33/49）， 73.33% （33/45）， and 77.27% （34/44） in the observation group， which were all higher than 45.83% （22/48）， 48.84% （21/43）， and 52.27% （23/44） in the control group. The difference was statistically significant （χ²=4.571， χ²=5.565， χ²=6.026， P<0.05）. The scores of EHP-5 and syndrome of cold congeal and blood stasis in the observation group were lower than those in the control group （P<0.01）. The levels of VEGF， MMP-9， IGF-1， NGF， SP， CGRP， and BDNF in the observation group were lower than those in the control group （P<0.01）， while the level of sFlt-1 was higher than that in the control group （P<0.01）. The levels of PGE₂， COX-2， TNF-α， and IL-6 in the observation group were lower than those in the control group （P<0.01）. The total effective rate of the observation group was 92.45% （49/53）， which was higher than 76.00% （38/50） of the control group （χ²=5.307， P<0.05）. After 6 months of follow-up， the recurrence rate in the observation group was 30.61% （15/49）， which was lower than 52.63% （20/38） in the control group （χ²=4.315， P<0.05）. The average of taking ibuprofen sustained-release capsules in the control group was higher than that in the observation group per menstrual period （P<0.01）. ConclusionModified Shaofu Zhuyutang treated pelvic pain of EMT with syndrome of cold congeal and blood stasis by regulating the mechanism of neural angiogenesis， reducing pain， and promoting the disappearance of related pains， thus improving the quality of life. Shaofu Zhuyutang has a better clinical effect than Aifu Nuangong pills and has a low recurrence rate.

This study aims to decipher the mechanism underlying the effect of Shaofu Zhuyu Decoction on endometriosis(EMT)-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis based on mitogen-and stress-activated protein kinase 1/2(MSK1/2).We employed a random number table to randomly assign SPF female non-pregnant rats into the sham group, and treated the rest rats with autologous transplantation+refrigerator freezing for the modeling of the syndrome of cold coagulation and blood stasis.The modeled rats were then randomly assigned into the control group and high-, medium-and low-dose Shaofu Zhuyu Decoction groups.The rats in the low-, medium-, and high-dose decoction groups were respectively administrated with 9, 4.5, and 2.3 g·kg~(-1) decoction through gavage once a day for 2 consecutive weeks, and those in the control group were administrated with 0.24 mg·kg~(-1) gestrinone through gavage once every 3 days for 2 weeks.After that, the size of ectopic focus in each rat was measured via laparotomy.Enzyme-linked immunosorbent assay(ELISA) was adopted to determine the expression of interleukin(IL)-6, IL-10, prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α).Western blot was employed to determine the protein levels of MSK1/2 and dual-specificity phosphatase 1(DUSP1) and real-time quantitative polymerase chain reaction(RT-PCR) to determine the mRNA levels of the two genes in rat eutopic endometrial tissue.Compared with the sham group, the model group showed increased levels of IL-6, PGE2, and TNF-α while decrease level of IL-10 in the serum(P<0.01).Compared with the model group, the high-and medium-dose decoction groups and the gestrinone group had declined levels of IL-6, PGE2, and TNF-α while risen level of IL-10 in the serum(P<0.01).The model group had lower protein levels and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the sham group(P<0.01). The high-and medium-dose decoction groups and the gestrinone group had higher protein and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the model group(P<0.01).The results indicated that Shaofu Zhuyu Decoction can regulate the abnormal expression of pro-inflammatory cytokines TNF-α, IL-6, and PGE2 and anti-inflammatory cytokines IL-10 and DUSP1 via MSK1/2 to alleviate EMT-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis.
Animals ; Female ; Rats ; Anti-Inflammatory Agents/therapeutic use* ; Cytokines ; Dinoprostone ; Drugs, Chinese Herbal/therapeutic use* ; Dual-Specificity Phosphatases ; Dysmenorrhea/genetics* ; Endometriosis/genetics* ; Gestrinone/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Mitogens/therapeutic use* ; RNA, Messenger ; Tumor Necrosis Factor-alpha/metabolism*

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) were searched for the effective components and targets of Shaofu Zhuyu Decoction. The relevant targets for endometriosis(EMT) and dysmenorrhea were retrieved from the Comparative Toxicogenomics Database(CTD), Therapeutic Target Database(TTD), GeneCards, and DisGeNET with the terms of "endometriosis" and "dysmenorrhea". Cytoscape 3.8.0 was employed to construct the drug-active component-therapeutic target network. A protein-protein interaction(PPI) network was established by STRING 11.0. Analyze Network, the plug-in in the Cytoscape 3.8.0, was used to calculate the topological parameters of the nodes and screen out the critical proteins in the network. The potential therapeutic targets were imported into RStudio and subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses with clusterProfiler package. Finally, the AutoDock Vina(Vina) platform was used for molecular docking to predict the binding degree of the main active components of Shaofu Zhuyu Decoction to key targets. As revealed by the screening results, 136 active components and 380 targets of Shaofu Zhuyu Decoction were obtained. Additionally, there were 1 627 targets related to EMT and 142 targets related to dysmenorrhea with 107 common targets, and 42 potential therapeutic targets of Shaofu Zhuyu Decoction for the treatment of EMT-induced dysmenorrhea. The targets such as interleukin 6(IL6) and prostaglandi-nendoperoxide synthase-2(PTGS2) were pivotal in the biological network of Shaofu Zhuyu Decoction intervention in EMT-induced dysmenorrhea, which involved multiple signaling pathways, including inflammation, hormones, and those promoted cell proliferation [e.g., mitogen-activated protein kinase(MAPK) and phosphatidylinositol-3 kinase(PI3 K)-protein kinase B(AKT)]. The results of molecular docking showed that the active components of Shaofu Zhuyu Decoction had good binding capacities to key targets such as IL6 and PTGS2. The findings of this study demonstrated that Shaofu Zhuyu Decoction could treat EMT-induced dysmenorrhea through multiple targets and multiple pathways, which could provide new ideas for investigating the underlying mechanism of Shaofu Zhuyu Decoction in the treatment of EMT-induced dysmenorrhea.
Drugs, Chinese Herbal ; Dysmenorrhea/genetics* ; Female ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology

OBJECTIVE: To study the association between clinical phenotypes and genotypes in children with Becker muscular dystrophy (BMD)/Duchenne muscular dystrophy (DMD) so as to provide a theoretical basis for disease management, gene therapy, and prenatal diagnosis. METHODS: A retrospective analysis was performed for the clinical data and gene detection results of 52 children with BMD/DMD. Multiplex ligation-dependent probe amplification (MLPA) was used to detect the DMD gene. The children with negative results of MLPA were further screened by exon chip capture combined with next-generation sequencing (NGS). The mothers of 20 probands were validated by sequencing. RESULTS: The pathogenic genes for BMD/DMD were detected in 50 children by MLPA and NGS, with a detection rate of 96%. Among the 52 children, 36 (69%) had gene deletion, 7 (13%) had duplication, and 7 (13%) had micromutation. Among the 43 children with deletion/duplication, 32 had DMD and 11 had BMD; 37 children (86%) met the reading frame rule, among whom 27 (96%) had DMD and 10 (67%) had BMD. All 7 children with micromutation had DMD. CONCLUSIONS The reading frame rule has an extremely high predictive value for DMD but a limited predictive value for BMD.
Child ; Dystrophin ; Female ; Gene Deletion ; Genotype ; Humans ; Multiplex Polymerase Chain Reaction ; Muscular Dystrophy, Duchenne ; Mutation ; Phenotype ; Pregnancy ; Retrospective Studies

Objective To understand the condition of tick carrying CRT(Candidatus rickettsia tarasevichiae) and compound infection with SFTSV(Sever fever thrombocytopenia syndrome virus) in Yanbian area of Jilin province. Methods Free ticks were collected from 6 counties including Yanji, Wangqing, Hunchun, Dunhua, Antu and Helong in the Korean Autonomous Prefecture of Jilin Province(Yanbian Prefecture) by using the flagging, and they were classified morphologically. The CRT and SFTSV in ticks were detected by Nest PCR(Nested polymerase chain reaction) and Real Time RT-PCR(Real-time Quantitative polymerase chain reaction) methods. Target DNA sequencing was performed for CRT positive products, and the homology of gene sequence and phylogenetic relationship were analyzed. Results A total of 1032 ticks were collected in this study, including ixodes persulcatus (35.56%) and dermacenter silvarum (20.64%). haemaphysalis japonica (20.45%), haemaphysalis longicornis (10.47%), haemaphysalis concinna (8.33%),others( 4.55%). The CRT was detected from the Ixodes persulcatus, Haemaphysalis longicornis, Haemaphysalis japonica Dermacentor silvarum. The MIR(Minimum infection rate per 100 ticks) of CRT was 10.47%.The SFTSV was detected from the Haemaphysalis-concinna, Haemaphysalis-japonica,Ixodes-persulcatus,Haemaphysalis-longicornis,Dermacentor-silvarum. The MIR of SFTSV was 2.52 %. Three species of ticks, including Ixodes persulcatus(2.45%), Haemaphysalis japonica(1.42%), and dermacentor silvarum(0.47%), had CRT and SFTSV compound infections, and the MIR of two pathogens compound infections was 1.26 %. In this study, the gene sequence of CRT positive PCR products ompA and 17kDa with nucleotide sequence of Xinyang plant of HeNan XinYang strain (KX365196.1),had homology of 100%. Phylogenetic analysis showed that CRT ompA and the HeNan XinYang strain (KX365196.1) gene sequences formed a cluster in Yanbian, while the 17 kDa gene formed an independent branch. Conclusions For the first time, CRT was detected from free ticks in Yanbian area of Jilin Province, and it was found that Ixodes persulcatus may be the main medium of transmission of the pathogen. At the same time, it was found that CRT and SFTSV have compound infection in ticks of Yanbian area. Therefore, it can be clearly identified that Yanbian area in Jilin Province is the natural source of CRT, and there are two pathogenic compound infections in the local ticks.

Objective To mastered the distribution characteristics of Haemaphysalis longicornis in the Tumen River basin along the border between Russia, Korea and Northeast China, and understand the status of Haemaphysalis longicornis carrying the virus of fever with thrombocytopenia syndrome (SFTS), then, isolate the virus and analyze its genetic characteristics. Method Ticks were collected from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Jilin Province from April to September, 2017. Haemaphysalis longicornis was selected and grouped. SFTS virus was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Virus isolation was carried out in Vero cells, besides, S,M,L gene segments were amplified . The homology of S, M and L gene segments was compared, phylogenetic tree was established, and their gene characteristics were analyzed. Result Haemaphysalis longicornis mainly distributed in Hunchun and Tumen City in the lower reaches of Tumen River. It was the dominant species in the two counties, reaching 71.85% and 87.62% respectively. A virus named YBHC-TICK2-2017/CHINA was isolated from Haemaphysalis longicornis collected in Hunchun. The sequences of S segment (1 746 bp), M segment (3 336 bp) and L segment (6 376 bp) of the virus were 98.00%-99.00%, homologous to those of SFTS virus isolates from China and Korea recorded in National Center for Biotechnology Information (NCBI) Gen Bank. Phylogenetic tree analysis showed that the S segment gene sequence of the virus strain was divided into a cluster with Jilin strain (KT890282) in China, and M segment and L segment gene sequence with Jiangsu strain (KR230781) in China. Conclusions Haemaphysalis longicornis are widely distributed in the lower reaches of the Tumen river. It was the first time that SFTS virus was isolated from Haemaphysalis longicornis in this area, suggesting that this area is important for SFTS prevention.

Objective:To explore clinical application effect of cardiac remote real -time monitoring system.Methods:Cardiac remote real -time monitoring warning instrument(iHolter)was applied in 210 patients.The iHolter gave a-lerts automatically in case of ECG abnormalities for corresponding treatment in time,and it offered corresponding reports on monitoring results.According to age,patients were divided into youth group(<45 years,n=59),mid-dle-aged group(45160 years,n=56)and aged group(≥60 years,n=95).Characteristics of arrhythmias among different age and sex were analyzed.Results:ECG abnormalities were found in 191 cases(90.95%)out of 210 pa-tients,including eight cases with malignant arrhythmias,in which five cases were treated and survived after timely intervention via alerts.Compared with youth group and middle -aged group,there were significant rise in percenta-ges of paroxysmal atrial tachycardia(16.9%,26.8% vs.54.7%)and atrial fibrillation(0%,0% vs.8.4%)in aged group,P< 0.05 or <0.01;abnormal percentages of heart rate variability of middle -aged group and aged group were significantly higher than that of youth group(25.0%,36.8% vs.5.1%,P<0.01 both).Male percent-age of paroxysmal ventricular tachycardia was significantly higher than that of female(81.3% vs.18.8%,P=0.013).Conclusion:Cardiac remote real-time monitoring system can offer timely alerts for cardiovascular events such as arrhythmia and myocardial ischemia etc.,fight for more time for rescuing patients,maximally protect cardi-ac function and improve accuracy of clinical diagnosis.

OBJECTIVETo investigate the effects of recombinant human growth hormone (rhGH) on the morphology and function of the left cardiac ventricle in young rats with dilated cardiomyopathy (DCM), and to evaluate the efficacy and safety of rhGH in the treatment of DCM.

METHODSSixty male Sprague-Dawley rats were randomly and equally assigned to control group, DCM group, and rhGH group. Furazolidone (0.25 mg/g) was given by gavage for 12 weeks to prepare the DCM model. Rats in the rhGH group received an intraperitoneal injection of rhGH (0.15 U/kg) once per day for 12 weeks, while rats in the DCM group received an equal volume of normal saline instead. Rats in the control group did not receive any treatment. Cardiac indices, serum biochemical parameters, hemodynamic indices, cardiac histopathological changes, and levels of myocardial collagen fibrils in each group were determined using Doppler echocardiography, enzyme-linked immunosorbent assay, multi-channel physiological recorder, light and electron microscopy, and picrosirius red staining plus polarization microscopy, respectively.

RESULTSCompared with the control group, rats in the DCM group had significantly increased cardiac chamber size, significantly reduced ventricular wall thickness, and significantly decreased fractional shortening (FS) and ejection fraction (EF) (P<0.05). Rats in the rhGH group had significantly improved cardiac chamber size, ventricular wall thickness, FS, and EF compared with the DCM group (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05). There were significant differences in serum biochemical parameters and hemodynamic indices between the DCM and control groups (P<0.05). Compared with the DCM group, the rhGH group had significantly improved serum biochemical parameters and hemodynamic indices (P<0.05). Those indices in the rhGH group were similar to those in the control group (P>0.05), except for the levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. The DCM group had a significantly higher collagen type I/collagen type III (Col I/Col III) ratio in the myocardium than the control group (P<0.05), and there was no significant difference in the Col I/Col III ratio between the control and rhGH groups (P>0.05).

CONCLUSIONSrhGH plays a certain role in improvement in the morphology and function of the left cardiac ventricle in young rats with DCM.

Animals ; Cardiomyopathy, Dilated ; drug therapy ; pathology ; Collagen Type III ; analysis ; Echocardiography ; Hemodynamics ; drug effects ; Human Growth Hormone ; therapeutic use ; Male ; Myocardium ; pathology ; ultrastructure ; Rats ; Rats, Sprague-Dawley