This study aims to investigate the mechanism of Mahuang Lianqiao Chixiaodou Decoction(MHLQ) and its main active components in treating immunoglobin A nephropathy(IgAN). The rat model of IgAN was established by a combination of measures including gavage of bovine serum albumin, subcutaneous injection of carbon tetrachloride, and tail vein injection of lipopolysaccharide. The modeled rats were randomized into model, low-, medium-, and high-dose(1.773, 3.545, and 7.090 g·kg~(-1), respectively) MHLQ, phillyrin(PHI, 0.020 g·kg~(-1)), pseudoephedrine(PSE, 0.020 g·kg~(-1)), and losartan potassium(LP, 9.003 mg·kg~(-1)) groups, and Wistar rats were used as the control. Rats were administrated with corresponding drugs by gavage, and those in the control and model groups received an equal volume of normal saline. All the groups were treated for 4 consecutive weeks. Urine, serum, liver, and kidney samples were collected from rats in each group at the end of drug administration. The 24 h urine protein and renal function were examined, and staining was performed to observe the pathological changes in the renal tissue. The immunofluorescence assay was employed to detect the expression of IgA and complement C3/C3b/C3c in the renal tissue. Electron microscopy was employed to observe the ultrastructure of the renal tissue. Enzyme-linked immunosorbent assay was performed to determine the expression of complement C3 and sublytic C5b-9 in the serum and renal tissue. Western blot was performed to determine the expression levels of hepatic and renal complement C3/C3b/C3c, C5/C5a, C5b-9, and complement factor B(CFB). Immunohistochemistry(IHC) was employed to measure the expression of complement C3 in the renal tissue. The results showed that compared with the control group, the model group had elevated levels of blood urea nitrogen and serum creatinine, proliferation of glomerular mesangial cells and extracellular matrix, and glomerular deposition of IgA immune complexes or electron-dense material. In addition, the model group showcased increased serum C3 levels and up-regulated expression of CFB, C3/C3b/C3c, C5/C5a, and C5b-9 in the renal tissue and C3/C3b/C3c and C5b-9 in the hepatic tissue. After treatment with MHLQ and its active components, all of the above indexes were reversed. In conclusion, MHLQ and its active components can improve the renal function and reduce the deposition of immune complexes and pathological damage in the renal tissue of the rat model of IgAN by inhibiting the alternative pathway complement activation.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Glomerulonephritis, IGA/genetics* ; Rats ; Male ; Disease Models, Animal ; Rats, Wistar ; Complement Activation/drug effects* ; Kidney/immunology* ; Humans

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate

OBJECTIVE: To analyze the Epstein-Barr virus (EBV) load in different lymphocyte subsets, as well as clinical characteristics and outcomes in patients with hematologic malignancies experiencing EBV reactivation. METHODS: Peripheral blood samples from patients were collected. B, T, and NK cells were isolated sorting with magnetic beads by flow cytometry. The EBV load in each subset was quantitated by real-time quantitative polymerase chain reaction (RT-qPCR). Clinical data were colleted from electronic medical records. Survival status was followed up through outpatient visits and telephone calls. Statistical analyses were performed using SPSS 25.0. RESULTS: A total of 39 patients with hematologic malignancies were included, among whom 35 patients had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median time to EBV reactivation was 4.8 months (range: 1.7-57.1 months) after allo-HSCT. EBV was detected in B, T, and NK cells in 20 patients, in B and T cells in 11 patients, and only in B cells in 4 patients. In the 35 patients, the median EBV load in B cells was 2.19×10⁴ copies/ml, significantly higher than that in T cells (4.00×10³ copies/ml, P <0.01) and NK cells (2.85×10² copies/ml, P <0.01). Rituximab (RTX) was administered for 32 patients, resulting in EBV negativity in 32 patients with a median time of 8 days (range: 2-39 days). Post-treatment analysis of 13 patients showed EBV were all negative in B, T, and NK cells. In the four non-transplant patients, the median time to EBV reactivation was 35 days (range: 1-328 days) after diagnosis of the primary disease. EBV was detected in one or two subsets of B, T, or NK cells, but not simultaneously in all three subsets. These patients received a combination chemotherapy targeting at the primary disease, with 3 patients achieving EBV negativity, and the median time to be negative was 40 days (range: 13-75 days). CONCLUSION In hematologic malignancy patients after allo-HSCT, EBV reactivation commonly involves B, T, and NK cells, with a significantly higher viral load in B cells compared to T and NK cells. Rituximab is effective for EBV clearance. In non-transplant patients, EBV reactivation is restricted to one or two lymphocyte subsets, and clearance is slower, highlighting the need for prompt anti-tumor therapy.
Humans ; Hematologic Neoplasms/virology* ; Herpesvirus 4, Human/physiology* ; Epstein-Barr Virus Infections ; Hematopoietic Stem Cell Transplantation ; Virus Activation ; Lymphocyte Subsets/virology* ; Flow Cytometry ; Killer Cells, Natural/virology* ; Male ; Female ; B-Lymphocytes/virology* ; Viral Load ; Adult ; T-Lymphocytes/virology* ; Middle Aged

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

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.

Objective To investigate the clinical characteristics and risk factors of delayed bleeding after intestinal polypectomy in children,and to provide a theoretical basis for clinical surgical intervention of intestinal polyps.Methods A retrospective analysis was conducted on the clinical data of 2 456 children with intestinal polyps who underwent endoscopic high-frequency electrocoagulation loop resection in the Endoscopy Center of Children's Hospital Affiliated to Zhengzhou University from January 2014 to December 2021.According to the presence or absence of delayed bleeding after surgery,they were divided into bleeding group with 79 children and non-bleeding group with 2 377 children.A multivariate logistic regression analysis was used to investigate the risk factors for delayed bleeding.The receiver operating characteristic(ROC)curve was used to investigate the value of various indicators in predicting delayed bleeding.Results Of all 2 456 children,79(3.22%)experienced delayed bleeding,among whom 5 children with severe delayed bleeding underwent emergency colonoscopy for hemostasis and 74 received conservative treatment,and successful hemostasis was achieved for all children.There were significant differences between the bleeding and non-bleeding groups in age,body mass index,constipation rate,location of lesion,time of endoscopic procedure,resection method(P<0.05).Children with a diameter of polyps of 6-10 mm and>20 mm were more likely to develop delayed bleeding after resection(P<0.05).The multivariate logistic regression analysis showed that endoscopic operation time,polyp diameter,and resection method were significantly associated with delayed bleeding(P<0.05).The ROC curve analysis showed that the endoscopic operation time,polyp diameter,and resection method had a good value in predicting delayed bleeding after intestinal polypectomy,with an area under the ROC curve of 0.706,0.688,and 0.627,respectively.Conclusions Endoscopic high-frequency electrocoagulation loop resection has a lower incidence of delayed bleeding in children with intestinal polyps,and the endoscopic operation time,polyp diameter,and resection method are closely associated with the occurrence of postoperative delayed bleeding.

Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

Objective To explore clinical effect of different intervertebral fusion devices(cage)in treating postoperative recurrent lumbar disc herniation(LDH).Methods One hundred and forty-two LDH patients with recurrence after simple in-tervertebral disc nucleus pulpoideectomy from January 2019 to January 2021 were retrospectively analyzed.All patients were treated with combined underchannel fixation and interbody fusion and divided into a single anatomical group,two-anatomical group and a single banana group according to types and numbers of implanted cage.There were 51 patients in a single anatom-ical group,included 29 males and 22 females,aged from 39 to 65 years old with an average of(53.74±5.68)years old;body mass index(BMI)ranged from 18.62 to 28.13 kg·m-2 with an average of(22.08±2.15)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 4.0 years with an average of(2.7±0.8)years;5 patients with L3,4,35 patients with L4,5 and 11 patients with L5S1;a single anatomical cage was implanted.There were 46 patients in two-anatomical group,included 25 males and 21 females,aged from 37 to 66 years old with an average of(54.52±6.02)years old;BMI ranged from 18.25 to 28.44 kg· m-2 with an average of(21.74±1.83)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.7±0.9)years;4 patients with L3,4,32 patients with L4,5 and 10 patients with L5S1;two-anatomical cages were im-planted.There were 45 patients in a single banana group,included 22 males and 23 females,aged from 38 to 65 years old with an average of(54.49±6.45)years old;BMI ranged from 18.85 to 28.20 kg·m-2with an average of(21.63±1.59)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.6±1.0)years;3 patients with L3,4,36 patients with L4,5 and 16 patients with L5S1;a single banana cage was implanted.Operation time,intraoperative blood loss,incision length,postoperative incision drainage volume,hospital stay and complications among 3 groups were observed and compared.The height of intervertebral space before and after operation,curvature of lordosis and the postoperative interverte-bral fusion were compared.Visual analogue scale(VAS)and Oswestry disability index(ODI)were used to evaluate degree of lumbar pain and lumbar function before operation,1 and 6 months after operation,respectively.Results All patients among 3 groups were followed up at least 6 months,and no cases were fell out.There were no significant difference in operation time,in-traoperative blood loss,incision length,postoperative incision drainage volume and hospital stay among 3 groups(P＞0.05).At 6 months after operation,the height of intervertebral space in two-anatomical group and a single group were[(11.08±1.78)mm,(10.95±1.62)mm],curvature of lordosis were[(12.05±1.86)°,(11.63±1.57)°],which were higher than those in a sin-gle dissection group(10.14±1.54)mm,(10.92±1.45)°,and the difference were statistically significant(P＜0.05).The inter-body fusion rate between two-anatomical and a banana group(95.65％,95.56％)were higher than that in a single anatomical group(78.43％)at 6 months after operation(P＜0.05).VAS and ODI of lumbar among 3 groups were decreased at 1 and 6 months after operation(P＜0.05).There was no significant difference in complications among 3 groups(P＞0.05).Conclusion The three fusion devices could achieve significant results in treating postoperative recurrence of LDH,but the implantation of two-anatomical cage and a single banana cage are more helpful to maintain the height of intervertebral space and lordosis cur-vature of patients with postoperative recurrence of LDH,and obtain good intervertebral fusion results.

Transcatheter aortic valve replacement(TAVR)is the use of interventional catheter to transport the artificial heart valve to the aortic valve area through the patient's arterial,venous system or left ventricular apex,then release it to replace the original aortic valve to achieve normal physiological function.The"suicide left ventricle"phenomenon refers to the paradoxical hemodynamic collapse of dynamic left ventricular obstruction caused by left ventricular hypertrophy and hypersystole after the removal of the fixed valve obstruction of aortic stenosis after TAVR.The clinical manifestation is abnormal continuous hypotension that is ineffective to positive inotropic drugs during the operation or within a few hours after the operation.With the indications for transcatheter aortic valve surgery covering patients with low,medium and high risk of severe aortic stenosis,surgery-related complications have been reported to increase gradually."Suicide left ventricle"is worth studying and exploring as a fatal potential complication.This article mainly reviews four aspects of the overview of"suicide left ventricle",pathological mechanism,risk-related indicators,prevention strategies and treatment methods to be highly vigilant and make corresponding emergency plans for patients with aortic stenosis who may have suicide left ventricle risk,so as to minimize perioperative mortality.