OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Objective:To analyze the correlation between ubiquitin-specific protease 9X(USP9X),ubiquitin-specific protease 25(USP25)and expression of proliferative and invasive genes in breast cancer tissues.Methods:A total of 158 breast cancer patients who were admitted to our hospital from August 2020 to July 2023 were selected,cancer tissues and paracancer tissues were collected,the mRNA expressions of USP9X,USP25,the mRNA expressions of proliferative genes and invasive genes in the different tissues were determined by real-time fluorescence quantitative polymerase chain reaction(RT-PCR),the relationship between mRNA expressions of USP9X,USP25,mRNA expressions of proliferative genes and invasive genes were analyzed by pearson correlation,the differences in mRNA expressions of USP9X,USP25 in cancer tissues of patients with different clinicopathological features of breast cancer were compared.Results:The mRNA expressions of USP9X,USP25,proliferating genome protein Methyltransferase(EZH)2,signal transduction and transcriptional activation factor 3(STAT3),Yes associated protein 1(YAP1),gene Dickkopf-related protein 1(DKK-1),taurine up-regulated gene 1(TUG1)and NUAK family kinase 1(NUAK1)in cancer tissue were higher than those of paracancer tissues(P＜0.05).Pearson correlation test showed that,the mRNA expressions of USP9X and USP25 were positively correlated with those of EZH2,STAT3,YAP1,DKK-1,TUG1 and NUAK1(P＜0.05),the mRNA expressions of USP9X and USP25 in cancer tissue of patients with TNM stage Ⅲ was higher than that of patients with stage Ⅰ-Ⅱ,and the mRNA expressions of USP9X and USP25 in cancer tissue of patients with lymph node metastasis was higher than that of patients without metastasis,the mRNA expressions of USP9X and USP25 in cancer tissue of patients with high Ki-67 expression were higher than those of patients with low KI-67 expression(P＜0.05).Conclusion:Elevated expressions of USP9X and USP25 in breast cancer tissues,which are closely associated with patients' proliferative genes and invasive genes expression,TNM stage,lymph node metastasis and Ki-67 expression.

Objective:To analyze the correlation between ubiquitin-specific protease 9X(USP9X),ubiquitin-specific protease 25(USP25)and expression of proliferative and invasive genes in breast cancer tissues.Methods:A total of 158 breast cancer patients who were admitted to our hospital from August 2020 to July 2023 were selected,cancer tissues and paracancer tissues were collected,the mRNA expressions of USP9X,USP25,the mRNA expressions of proliferative genes and invasive genes in the different tissues were determined by real-time fluorescence quantitative polymerase chain reaction(RT-PCR),the relationship between mRNA expressions of USP9X,USP25,mRNA expressions of proliferative genes and invasive genes were analyzed by pearson correlation,the differences in mRNA expressions of USP9X,USP25 in cancer tissues of patients with different clinicopathological features of breast cancer were compared.Results:The mRNA expressions of USP9X,USP25,proliferating genome protein Methyltransferase(EZH)2,signal transduction and transcriptional activation factor 3(STAT3),Yes associated protein 1(YAP1),gene Dickkopf-related protein 1(DKK-1),taurine up-regulated gene 1(TUG1)and NUAK family kinase 1(NUAK1)in cancer tissue were higher than those of paracancer tissues(P＜0.05).Pearson correlation test showed that,the mRNA expressions of USP9X and USP25 were positively correlated with those of EZH2,STAT3,YAP1,DKK-1,TUG1 and NUAK1(P＜0.05),the mRNA expressions of USP9X and USP25 in cancer tissue of patients with TNM stage Ⅲ was higher than that of patients with stage Ⅰ-Ⅱ,and the mRNA expressions of USP9X and USP25 in cancer tissue of patients with lymph node metastasis was higher than that of patients without metastasis,the mRNA expressions of USP9X and USP25 in cancer tissue of patients with high Ki-67 expression were higher than those of patients with low KI-67 expression(P＜0.05).Conclusion:Elevated expressions of USP9X and USP25 in breast cancer tissues,which are closely associated with patients' proliferative genes and invasive genes expression,TNM stage,lymph node metastasis and Ki-67 expression.

Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Objective Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist with sedative and analgesic properties but without respiratory depression effect and has been widely used in perioperative anesthesia. Here we performed a systematic review and meta-analysis to evaluate the effect of dexmedetomidine on maintaining perioperative hemodynamic stability in elderly patients.Methods PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched for randomized-controlled trials (RCTs) on the application of dexmedetomidine in maintaining perioperative hemodynamic stability in elderly patients from their inception to September, 2021. The standardized mean differences (SMD) with 95% confidence interval (CI) were employed to analyze the data. The random-effect model was used for the potential clinical inconsistency.Results A total of 12 RCTs with 833 elderly patients (dexmedetomidine group, 546 patients; control group, 287 patients) were included. There was no significant increase in perioperative heart rate (HR), mean arterial pressure (MAP), and diastolic blood pressure (DBP) in the dexmedetomidine group before and during the operation. In addition, the variations of hemodynamic indexes including HR, MAP, SBP (systolic blood pressure), and DBP were significantly lower in the dexmedetomidine group compared with the control group (HR: SMD = -0.87, 95% CI: -1.13 to -0.62; MAP: SMD = -1.12, 95% CI: -1.60 to -0.63; SBP: SMD = -1.27, 95% CI: -2.26 to -0.27; DBP: SMD = -0.96, 95% CI: -1.33 to -0.59). Subgroup analysis found that with the prolongation of 1.0 μg/kg dexmedetomidine infusion, the patient's heart rate declined in a time-dependent way.Conclusion Dexmedetomidine provides more stable hemodynamics during perioperative period in elderly patients. However, further well-conducted trials are required to assess the effective and safer doses of dexmedetomidine in elderly patients.
Humans ; Aged ; Dexmedetomidine/adverse effects* ; Hemodynamics ; Hypnotics and Sedatives/pharmacology* ; Blood Pressure ; Heart Rate

Objective:To investigate the distribution of HIV-1 genotypes and drug resistance in newly diagnosed HIV-1 patients in Baoding in 2020.Methods:A self-developed method was used to amplify the pol gene sequence of HIV-1, and the sequencing results were analyzed by phylogenetic analysis and compared with the Stanford drug resistance database to determine the HIV-1 subtypes and gene mutations. Results:A total of 96 patients with HIV-1 infection were recruited in this study, and 83 pol gene sequences were successfully obtained. In the study population, 88 (91.7%) were male with an average age of 39 years and 54 (56.3%) were married. Most of the patients were infected through sexual contact (95.8%, 92/96), and 75.0% (72/96) were through homosexual transmission. Phylogenetic analysis showed that various HIV-1 subtypes were detected and among them, CRF01_AE (51.8%, 43/83), CRF07_BC (24.1%, 20/83) and B subtype (10.8%, 9/83) were the most epidemic strains. Moreover, the subtypes of newly identified recombinant strains in recent years accounted for 13.3% (11/83). Drug resistance test results showed that the pre-treatment drug resistance rate in newly diagnosed HIV-1 patients was 8.4% (7/83), and the drug resistance rates to protease inhibitor (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase inhibitors (INIs) were 3.6% (3/83), 1.2% (1/83) and 3.6% (3/83), respectively. Conclusions:The HIV-1 subtypes in the newly diagnosed population in Baoding in 2020 were complex and diverse. There were many unique recombinant strains and drug-resistant strains. Therefore, it was necessary to strengthen drug resistance monitoring as well as the prevention and control of HIV-1 infection in this area.