Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.

Amino acid surfactants (AAS) have excellent properties such as low toxicity,antibacterial,mildness,and corrosion resistance. In recent years,they have been widely applied in the field of daily chemicals,food and pharmaceutical industry. It is pointed out that the structure at molecular level largely affects the physical and chemical properties of AAS materials. In this work,the structures of solid-state N-lauroyl-L-alanine (NLLA) including intermolecular interactions,molecular local dynamics and molecular assembly were investigated by a variety of solid-state nuclear magnetic resonance (SSNMR) techniques. Based on 2D 1H-1H double quantum-single quantum (2D 1H-1H DQ-SQ),1H-1H DQ sideband pattern and molecular simulation,it was found that there was a stable intermolecular hydrogen bond formed between the carboxyl units of two NLLA molecules. Combined with the study of 2D frequency switched Lee—Goldberg heteronuclear correlation (2D 13C-1H FSLG-HETCOR) and 13C T1,another type of hydrogen bond was probed,which existed between amide units of neighboring molecules. In addition,the conformation of alkyl chain ends was investigated. According to 1D 13C{1H}cross polarization/magic angle spinning (CP/MAS) and 2D 13C-1H FSLG-HETCOR spectra,it was revealed that the alkyl-chain ends had both gauche and trans conformations. Moreover,the trans conformation showed two distinct 13C chemical shifts,originated from two NLLA molecular assembly forms. Accordingly,two NLLA molecular assembly structures were suggested which were transoid form and cisoid form. This work provided a SSNMR investigation strategy for characterizing the molecular local structure and dynamics of AAS materials,which helped task of researching and developing materials with improved chemical and physical properties.

Objective:This study aims to evaluate the clinical efficacy and safety of Dibai Yijing Formula(DYF)in the treat-ment of male infertility with essence deficiency in the kidney and damp-heat in the essence chamber(Abbreviation:kidney deficiency and damp-heat type).Methods:This study employed a randomized,controlled clinical trial design,recruiting 72 male patients with infertility due to kidney deficiency and damp-heat type.Patients were randomly assigned to an treatment group(36 patients)and a control group(36 patients)using a random number table.The control group received oral Clomiphene Citrate Capsules(50 mg,twice daily),while the treatment group received oral DYF(one dose daily,200 ml each time,30 minutes after breakfast and dinner).Both groups underwent a 12-week treatment period.After treatment,sperm concentration(SC),percentage of progressively motile sperms(PR),total sperm motility[PR+percentage of non-progressively motile sperms(NP)],and semen volume(SV)were compared between the two groups before and after treatment.Additionally,the total score of Traditional Chinese Medicine(TCM)syndrome score and sperm DNA fragmentation index(DFI)and pregnancy outcomes of the patients'spouses were compared between the two groups.Results:Three patients dropped out from the treatment group and four from the control group.There were no statistically sig-nificant differences in semen parameters between the two groups(P＞0.05).After treatment,the patients in the treatment group showed significant difference in the percentage of SC([19.42±5.30]x 106/ml vs[10.75±2.41]x 106/ml),PR([27.72±6.62]％vs[20.04±4.10]％),PR+NP([49.86±10.68]％vs(33.74±5.58)％],DFI([12.33±3.43]％vs[15.06±3.98]％)and TCM symtom score([7.45±1.82]vs[13.85±1.91]),and the difference was statistically significant(P＜0.05).The patients in the control group showed significant difference in the percentage of SC([19.56±5.24]× 106/ml vs[11.31±2.08]× 106/ml)and TCM symptom score([12.81±1.86]vs[14.06±1.64]).But no significant changes were observed in the PR([21.75±5.93]％vs[20.05±4.67]％),PR+NP([34.23±7.15]％vs[32.35±4.09]％),SV([3.19±1.08]ml vs[3.12±1.13]ml),and DFI([15.11±4.76]％vs[15.51±4.35]％)were not statistically significant(P＞0.05).Improve-ments in PR,PR+NP,TCM symptom score and DFI in the treatment group were better than those in the control group after treatment(P＜0.05);the differences in SC and SV and spousal pregnancy in the treatment group were not statistically significant compared with those in the control group(P＞0.05).No serious adverse events occurred in both groups during the treatment period.Conclusion:The treatment of male infertility with DYF is effective and safe.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:To investigate the correlation between morphological typing and monoclonality of bone marrow plasma cells,and explore the diagnostic value of plasma cell morphological typing for high-risk smoldering multiple myeloma(HR-SMM).Methods:The correlation between the morphological characteristics and the monoclonality of bone marrow plasma cells was analyzed in 84 patients with HR-SMM who treated in our hospital.The consistency of morphologically abnormal bone marrow plasma cells with serum free light chain(sFLC)ratio,next-generation sequencing(NGS)detection results,and its correlation with monoclonal plasma cells detected by flow cytometry(FCM)were further verified.The immunoglobulin types and levels of non-involved immunoglobulins in serum of the patients were detected,and the distribution of plasma cell clusters in patients with different disease was observed.Results:The mean percentage of mature plasma cells were decreased successively in the order of reactive plasmacytosis(RP)group,monoclonal gammopathy of undetermined significance(MGUS)group,smoldering multiple myeloma(SMM)group,HR-SMM group and multiple myeloma(MM)group;while the mean percentage of immature,primitive,reticular and flaming plasma cells were increased successively in the order of RP group,MGUS group,SMM group,and HR-SMM group,and the difference between any two groups was statistically significant(P＜0.05).The average proportion of abnormal plasma cells in the bone marrow of HR-SMM patients was 96.2％of the total plasma cells.The proportion of abnormal plasma cells were in good agreement with the sFLC ratio and the results of NGS detection in HR-SMM patients(kappa=0.879 and kappa=0.891,both＞0.75),and showed good correlation with the monoclonal plasma cells with immunophenotype of CD45-/CD38+/CD138+/CD56+/CD19-(γ=0.825).The levels of non-involved immunoglobulin in IgG,IgA and IgM type HR-SMM patients were all decreased by more than 25％compared with the normal reference range,and the differences were statistically significant(P＜0.05).There was no significant difference in the distribution ratio of plasma cell clusters among different disease groups(P＞0.05).Conclusion:In HR-SMM patients,the immature,primitive,reticular and flaming plasma cells in bone marrow are considered as abnormal plasma cells,and they are correlated with monoclonal plasma cells.The proportion of abnormal plasma cells in total plasma cells of bone marrow and the reduction extent of non-involved immunoglobulin level in patients have certain reference value for the diagnosis of HR-SMM.

Objective To investigate the value of quantitative CT(QCT)parameters related to abdominal and dorsal fat content for predicting early postoperative complications of esophageal cancer.Methods A total of 184 patients who underwent radical esophageal cancer surgery were retrospectively collected and divided into complication group(n=76)and control group(n=108)according to whether early postoperation complication(within 30 days after surgery)occurred or not.QCT was used to obtain parameters related to abdominal and dorsal fat content,including visceral fat area(VFA),subcutaneous fat area(SFA),VFA/SFA and the degree of muscle fat infiltration(MFI)of posterior vertebral muscles based on L3 central-level CT images.Univariate analysis and multivariate logistic regression were used to analyze clinical and pathological data as well as QCT parameters related to abdominal and dorsal fat content to screen independent risk factors for early postoperative complications of esophageal cancer.Then receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of each independent risk factor alone and their combination for predicting early postoperative complications of esophageal cancer.Results VFA/SFA and MFI degree of posterior vertebral muscles were both independent risk factors for early postoperative complications of esophageal cancer(OR=5.121,1.110,both P＜0.05).The AUC of VFA/SFA and MFI degree of posterior vertebral muscle was 0.81 and 0.77,respectively,while of their combination was 0.84.Conclusion QCT parameters related to abdominal and dorsal fat content could be used to effectively predict early complications of esophageal cancer after surgery.

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.
Humans ; Acupuncture Therapy ; Periosteum ; Analgesia ; Pain Management ; Consciousness ; Pain

This study investigated the effects of Xuefu Zhuyu Decoction on myocardial metabolites in a rat model of coronary heart disease with heart blood stasis syndrome and explored the therapeutic mechanism of blood circulation-promoting and blood stasis-removing therapy. SD rats were randomly divided into a sham operation group, a model group, a Xuefu Zhuyu Decoction group(14.04 g·kg~(-1)), and a trimetazidine group(5.4 mg·kg~(-1)). The sham operation group underwent thread insertion without ligation, while the other groups underwent coronary artery left anterior descending branch ligation to induce a model of coronary heart disease with heart blood stasis syndrome. Three days after modeling, drug intervention was performed, and samples were taken after 14 days of intervention. General conditions were observed, and electrocardiogram and cardiac ultrasound indices were measured. Hematoxylin-eosin(HE) staining and Masson staining were used to observe tissue pathological morphology. The enzyme linked immunosorbent assay(ELISA) was used to measure the levels of triglyceride(TG) and total cholesterol(TC) in the serum. Ultra high performance liquid chromatography-quantitative exactive-mass spectrometry(UHPLC-QE-MS) technology was used to screen differential metabolites in myocardial tissue and conduct metabolic pathway enrichment analysis. The results showed that Xuefu Zhuyu Decoction significantly improved the general condition of the model rats, reduced heart rate and ST segment elevation in the electrocardiogram, increased left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), and decreased left ventricular internal diameter in diastole(LVIDd) and left ventricular internal diameter in systole(LVIDs). HE staining and Masson staining showed that Xuefu Zhuyu Decoction effectively alleviated myocardial tissue structural disorders, inflammatory cell infiltration, and collagen fiber deposition in the model rats. ELISA results showed that Xuefu Zhuyu Decoction effectively regulated serum TG and TC levels in the model rats. There were significant differences in the metabolic phenotypes of myocardial samples in each group. Fourteen differential metabolites were identified in the Xuefu Zhuyu Decoction group, involving five metabolic pathways, including arginine and proline metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, ether lipid metabolism, and alanine, aspartate, and glutamate metabolism. Xuefu Zhuyu Decoction improved cardiac function and myocardial structural damage in the rat model of coronary heart disease with heart blood stasis syndrome, and its biological mechanism involved the regulation of lipid metabolism, choline metabolism, amino acid metabolism, energy metabolism, and protein synthesis pathways.
Rats ; Animals ; Stroke Volume ; Rats, Sprague-Dawley ; Ventricular Function, Left ; Coronary Disease/drug therapy* ; Metabolomics

OBJECTIVE: To explore the value of multiple detection methods based on histopathology and supplemented by bone marrow or peripheral blood sample detections in the comprehensive diagnosis of mantle cell lymphoma (MCL). METHODS: The clinical, immunophenotypic, pathologic, cytogenetic and molecular features of 153 newly diagnosed MCL patients admitted to the hematology department of our hospital from May 2009 to September 2022 were analyzed. RESULTS: 144 (96.6%) of the 149 MCL patients who underwent marrow or peripheral blood IGH/CCND1 FISH detection at initial diagnosis were positive, of which 36 cases (24.2%) had a low proportion positive. The immunophenotypes in 115 patients were analyzed by flow cytometry (FCM), 89 cases (77.4%) conformed to MCL while 23 cases (20.0%) were initially diagnosed as B-cell lymphoproliferative disorders (B-LPD). Of the 75 cases who performed bone marrow biopsy, 50 cases (66.7%) had morphological and immunophenotypic characteristics consistent with MCL, 15 cases (20.0%) were classified as B-LPD, and 10 cases with no obvious abnormality. 77 patients underwent histopathology examination, of which 73 cases (94.8%) had typical clinicopathological features of MCL, including 2 CCND1 negative MCL, 2 pleomorphic variants, 5 pleomorphic variants and 4 cases diagnosed as other leukemia or lymphoma. Among 153 cases of MCL, 128 cases were classic MCL(cMCL), and another 25 cases (16.3%) were diagnosed as leukemic non-lymph node MCL (lnnMCL). The incidence of IGHV mutation, TP53 mutation and CD23 expression positive were significantly different between cMCL and lnnMCL. CONCLUSION Histopathology is still the main standard for the diagnosis of cMCL, and detection based on bone marrow or peripheral blood samples is an important means for the diagnosis of lnnMCL. Single marker or examination can cause a certain proportion of misdiagnosis. The accurate diagnosis of MCL depends on a combination of multiple detection methods.
Adult ; Humans ; Lymphoma, Mantle-Cell/genetics* ; Bone Marrow/pathology* ; Leukemia/pathology* ; Mutation ; Immunophenotyping