This article reports the clinical features and gene mutation types of a large family with Nascimento form of syndromic X-linked intellectual developmental disorder (MRXSN), involving 9 individuals across 3 generations, and a literature review was conducted. In this family, 9 individuals had similar manifestations including mental retardation and unusual facies, and 4 of them had passed away. Genetic testing showed that the proband had the deletion of exons 2-3 of the UBE2A gene, which was inherited from the mother. Fluorescent quantitative polymerase chain reaction showed that the proband and his uncle had the deletion of exons 2-3 of the UBE2A gene; the proband's mother, grandmother, and great-aunt had a heterozygous deletion of exons 2-3 of the UBE2A gene; the proband's father, sister, and aunt had a normal copy number of exons 2-3 of the UBE2A gene. The 34 patients reported in the literature had diverse clinical phenotypes, and UBE2A gene mutations (22/34, 65%) and large fragment deletions (12/34, 35%) were the main mutation types. Moderate to severe mental retardation (34/34, 100%), speech and language impairment (33/34, 97%), and unusual facies (32/34, 94%) were the main clinical manifestations of MRXSN patients. The disease has obvious phenotypic heterogeneity, and early diagnosis facilitates optimal prenatal and postnatal management to improve reproductive outcomes.
Humans ; Male ; Ubiquitin-Conjugating Enzymes/genetics* ; Female ; X-Linked Intellectual Disability/genetics* ; Gene Deletion ; Child ; Pedigree ; Child, Preschool ; Adult

OBJECTIVE: To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone (T) synthesis and the hypothalamic-pituitary-gonadal (HPG) axis in naturally aged mice. METHODS: We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months, randomized them into a moxibustion and an aged group of an equal number, and selected 7 four-month-old ones as young controls. We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point, once 5 moxibustion sticks, qd, 5 times a week, and fed those of the aged group normally, all for 12 weeks. After treatment, we obtained the testicular index of the mice, observed the histomorphology of the testis tissue by HE staining, measured the contents of T in the testis, gonadotropin-releasing hormone (GnRH) in the hypothalamus and total T (tT), free T (fT), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum by ELISA, and determined the expressions of silence information regulator-1 (SIRT1), P53, glutathione peroxidase (GPX4) and cholesterol side-chain?cleavage enzyme (CYP11A1) in the testis by Western blot. RESULTS: Compared with the young controls, the mice in the aged group showed obviously losing and dull hair, energy declination, loose structure of the spermatogenic tubule with different degrees of cell loss and rupture, reduced testicular index, and evident aging phenotype. In comparison with the aged mice, the animals of the moxibustion group were fairly energetic and exhibited distinct structure of the spermatogenic tubules, orderly arranged and highly differentiated cells at all levels, significantly increased T level, up-regulated expressions of SIRT1, GPX4 and CYP11A1, and down-regulated expression of P53 in testis tissue, and elevated levels of GnRH, FSH, LH, tT and fT in the HPG axis. CONCLUSION Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice, promotes negative feedback regulation of the HPG axis, and improves low testosterone.
Animals ; Male ; Moxibustion ; Mice ; Testosterone/metabolism* ; Mice, Inbred C57BL ; Testis/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Triticum ; Gonadotropin-Releasing Hormone/metabolism* ; Luteinizing Hormone/blood* ; Follicle Stimulating Hormone/blood* ; Aging ; Hypothalamus/metabolism* ; Acupuncture Points ; Sirtuin 1/metabolism* ; Hypothalamic-Pituitary-Gonadal Axis

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

OBJECTIVE To compare the efficacy and safety between the drug winning the bidding for centralized procurement and the original drug of ticagrelor in acute coronary syndrome （ACS） patients one year after percutaneous coronary intervention （PCI）. METHODS Overall 420 ACS patients treated with PCI in our hospital from July 2021 to June 2023 were divided into centralized procurement group （156 cases） and original drug group （264 cases） according to the different varieties of ticagrelor. All patients were given Aspirin enteric-coated tablets 100 mg regularly， once a day； on this basis， patients in the centralized procurement group were given Ticagrelor tablets winning the bidding， while patients in the original drug group were given the original drug of Ticagrelor tablets. The dosage of Ticagrelor tablets taken by both groups of patients was 90 mg， twice a day， and the course of treatment was 12 months. The blood routine indicators were compared before treatment and one week after treatment， while the incidence of net adverse clinical events （NACE）， major adverse cardiovascular and cerebrovascular events （MACCE） and bleeding events， and the survival rate without MACCE and bleeding events during a one-year follow-up after PCI were also compared between two groups. RESULTS There were no statistically significant differences in blood routine indicators before treatment and one week after treatment， as well as the incidence of NACE， MACCE and bleeding events， survival rate without MACCE and bleeding events during a one-year follow-up after PCI between the two groups （P＞0.05）. CONCLUSIONS During a one-year follow-up after PCI， the efficacy and safety of the drug winning the bidding for centralized procurement of ticagrelor are comparable to the original drug.

Objective·To investigate the potential causal relationship between type l diabetes and colorectal cancer by using Mendelian randomization(MR).Methods·Two-sample bidirectional MR was used to investigate the causal relationship between type 1 diabetes and colorectal cancer.All research data were collected from the IEU Open GWAS Project database.The dataset of type l diabetes included 9 266 cases and 15 574 controls,with correlation analysis in 12 783 129 single nucleotide polymorphisms(SNPs);the dataset of colorectal cancer included 5 657 cases and 372 016 controls,with correlation analysis in 29 999 696 SNPs.The instrumental variables SNPs were screened.The results derived from the inverse-variance weighted(IVW)method were used as the main indicator of effect.The results derived from other four methods,namely MR-Egger regression,weighted median,simple mode,and weighted mode,were used as reference.Sensitivity was analyzed with the leave-one-out method.Heterogeneity was analyzed with Cochran's Q test by using both IVW and MR-Egger methods.Pleiotropy was analyzed with MR-pleiotropy function,and Steiger test was used for directional research.The colocation analysis was used to find out whether the causal relationship between type 1 diabetes and colorectal cancer was caused by the same SNP.The genetic correlation between 2 diseases was analyzed by using the linkage disequilibrium score regression(LDSC).All tests were analyzed by using R language software(version 4.3.1).Results·After being screened,a total of 33 instrumental variables(SNPs)were used.The heterogeneity test results showed that there was heterogeneity among the SNPs(IVW and MR-Egger:P＜0.05),so the effect evaluation was based on the results of the random effect model.MR analysis showed that type 1 diabetes had a significant causal effect on colorectal cancer(P＜0.05)by using IVW,MR-Egger,weighted median and weighted mode.Sensitivity analysis showed that the results were stable.Pleiotropy was not detected in pleiotropy test(P＞0.05).Steiger test showed that the effect of type l diabetes on colorectal cancer was not interfered with by the reverse effect.Reverse MR analysis showed no causal effect of colorectal cancer on type l diabetes(P＞0.05).The results of colocalization analysis showed that the probability of H4 hypothesis was 45.7％,and the causal relationship between the 2 diseases was not caused by the same SNP in the gene sequences.LDSC analysis demonstrated that there was no genetic correlation between the two diseases.Conclusion·Type 1 diabetes may promote colorectal cancer,but colorectal cancer has no effect on type 1 diabetes.

Objective To summarise and analyse the qualitative studies on the factors that influence patient involvement in decision-making for the initial administration of insulin for the patients with Type II diabetes,from the perspectives of patients and healthcare staff in order to provide a reference to promote patient involvement in decision-making.Methods Systematic searches were conducted across databases,such as CINAHL,Cochrane Library,EMBASE,PubMed,Web of Science,PsycINFO,China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,and SinoMed,for qualitative studies on the factors that affect patient involvement in initial insulin decision-making for the patients with Type II diabetes.The search was limited to articles from the inception of the databases to 30th September,2023.Quality of the included studies was assessed using the Joanna Briggs Institute(JBI)evidence-based healthcare centre for qualitative research quality assessment tool.The results were integrated using a synthesising integration method.Results A total of 19 articles were included,yielding 20 study results,which were categorised into 7 themes of patient decision-making related values,patient role preferences in decision-making,condition of patient,the role of healthcare staff in patient participation in decision-making,professional quality of healthcare staff,relationship between patient and healthcare staff,and the support from a medical institution.The data were ultimately integrated into 4 overarching themes of patient personal factors,healthcare staff factors,patient-staff interaction factors and medical institution factors.Conclusion The involvement of the patients with Type II diabetes in the decision-making for the initial administration of insulin is influenced by patients themselves,healthcare staff and medical institutions.It requires efforts of multiple parties:not only with the patients actively participate in decision-making,but also with the healthcare staff and institutions who provide effective decision supports.