Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

Objective:To study the expressions of C-C class chemokine 17 (CCL17), C-C class chemokine 22 (CCL22), and C-C chemokine receptor 4 (CCR4) in newly diagnosed multiple myeloma (NDMM) for analyzing their correlations with clinical features and to preliminarily explore their roles in the development of NDMM.Methods:The study included 40 patients with NDMM and 20 healthy volunteers from the Department of Hematology of the Affiliated Hospital of Zunyi Medical University from July 2020 to December 2022. Peripheral blood, bone marrow, and bone marrow biopsy tissue samples were collected from the two groups. The expression levels of CCL17, CCL22, and CCR4 in patients with NDMM were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The mRNA expression levels of CCL17, CCL22, and CCR4 in the bone marrow mononuclear cell (BMMNC) of patients with NDMM were analyzed to assess their correlations with clinical indicators.Results:The mRNA expression levels of CCL17, CCL22, and CCR4 in BMMNC were higher in patients with NDMM than in controls (all P<0.05). The protein expression levels of CCL17 and CCL22 in peripheral blood supernatants and bone marrow supernatants were higher in patients with NDMM than in controls (all P<0.05). The expression levels of CCL17, CCL22, and CCR4 in bone marrow biopsy tissues were higher in patients with NDMM than in controls (all P<0.05). The mRNA expression level of CCL17 was increased in NDMM patients with combined anemia, bone damage, renal damage, and M protein level ≥30 g/L (all P<0.05). The mRNA expression level of CCL22 was increased in NDMM patients with combined anemia, bone damage, and renal damage (all P<0.05). The mRNA expression level of CCR4 was increased in NDMM patients with combined anemia and renal damage (all P<0.05) . Conclusion:CCL17, CCL22, and CCR4 were highly expressed in clinical samples from patients with NDMM compared to those from controls, and they may be involved in the occurrence and development of NDMM.

Objective To observe the clinical efficacy of closed-loop rehabilitation therapy by brain-computer interface(BCI)combined with exoskeleton robotic hand in patients with hand dysfunction after cerebral infarction and analyze the influence of patients'cognitive function and implicit motor imagery ability on the recognition rate of BCI.Methods A total of 50 patients with cerebral infarction were randomly assigned to the observation group and the control group,25 patients in each group.Both groups received routine rehabilitation programs.In addition to the conventional rehabilitation treatment,the observation group received the closed-loop BCI rehabilitation trainingby brain-computer interface(BCI)combined with exoskeleton robotic hand.The scores of Fugl-Meyer Assessment of the Upper Extremity(FMA-UE),Action Research Arm Test(ARAT),Wolf Motor Function Test(WMFT),and Modified Ashworth scale(MAS)of the wrist flexors were compared between the two groups before and after treatment.Before intervention,the mental rotation test and Montreal Cognitive Assessment(MoCA)were used to assess the baseline implicit motor imagery ability and cognitive level of patients in the observation group.The correlation analysis between these scores and the recognition rate of BCI was conducted to analyze the relevant factors affecting the closed-loop rehabilitation effects of BCI.Results The two groups showed no significant difference in all outcomes before treatment(both P>0.05).After intervention,the observation group exhibited the significantly higher scores of FMA-UE,ARAT,and WMFT(all P<0.05),and significantly lower MAS scores of wrist and finger flexors compared with the control group(all P<0.05).In addition,the recognition rate of BCI was positively correlated with the accuracy of mental rotation test and MoCA score(P<0.05),and negatively corre-lated with the reaction time of mental rotation test(P<0.05).Conclusions Closed-loop rehabilitation training with BCI combined with exoskeleton robot hand can promote the recovery of upper limbs and hand motor function in patients with cerebral infarction.Additionally,the implicit motor imagery ability and cognitive function of patients are suggested to be used for screening the patients suitable for BCI training before the implementation of BCI treatment.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.
Animals ; Mice ; Biological Products ; Chromatography, High Pressure Liquid ; Coleoptera ; Cyclooxygenase 2 ; Diarrhea/drug therapy* ; Antineoplastic Agents

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.
Humans ; Acidosis, Lactic/genetics* ; Electron Transport Complex III/genetics* ; Retrospective Studies ; Mutation ; Growth Disorders ; ATPases Associated with Diverse Cellular Activities/genetics*

DMRT, a gene family related to sexual determination, encodes a large group of transcription factors (DMRTs) with the double-sex and mab-3 (DM) domain (except for DMRT8), which is able to bind to and regulate DNAs. Current studies have shown that the DMRT gene family plays a critical role in the development of sexual organs (such as gender differentiation, gonadal development, germ cell development, etc.) as well as extrasexual organs (such as musculocartilage development, nervous system development, etc.). Additionally, it has been suggested that DMRTs may be involved in the cancer development and progression (such as prostate cancer, breast cancer, lung cancer, etc.). This review summarizes the research progress about the mammalian DMRTs' structure, function and its critical role in cancer development, progression and therapy (mainly in human and mice), which suggests that DMRT gene could be a candidate gene in the study of tumor formation and therapeutic strategy.
Male ; Animals ; Humans ; Mice ; Transcription Factors/genetics* ; Mammals/metabolism* ; Cell Differentiation ; Neoplasms/genetics*

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Liver ; Lipoproteins, LDL/metabolism* ; Signal Transduction ; Diet, High-Fat/adverse effects* ; RNA, Messenger/metabolism*

This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.
Humans ; Ferroptosis ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Epithelial Cells ; Antioxidants ; Glutathione ; Glucose