OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVE: To explore the clinical features of the sepsis in immunocompromised hosts and establish an early warning equation. METHODS: A retrospective study was conducted on sepsis patients admitted to the intensive care unit (ICU) of Binzhou Medical University Hospital from October 2011 to October 2022. General information, infection site, etiology results and drug susceptibility, clinical symptoms, inflammatory indicators, acute physiology and chronic health status evaluation II (APACHE II), sequential organ failure assessment (SOFA), incidence of immune paralysis, and outcome during hospitalization were collected. Based on whether they met the diagnostic criteria for immunocompromised hosts, patients were divided into immunocompromised group and immune normal group. The clinical information of the two groups were compared. Multivariate Logistic regression was used to analyze the risk factors of patients with immunocompromised sepsis and the regression equation model was initially established. Omnibus test and Hosmer-Lemeshow test were used to evaluate the model. RESULTS: A total of 169 patients with sepsis were included, including 61 in the immunocompromised group and 108 in the normal immune group. The top 3 infection sites in the immunocompromised group were bloodstream infection, pulmonary infection and abdominal infection. The top 3 infection sites in the normal immune group were pulmonary infection, bloodstream infection and abdominal infection. The infection rate of Gram-negative bacteria in the immunocompromised group was significantly lower than that in the normal group [49.2% (30/61) vs. 64.8% (70/108), P < 0.05]. The infection rate of Gram-positive bacteria [27.9% (17/61) vs. 13.9% (15/108)] and multidrug-resistant bacteria [54.1% (33/61) vs. 29.6% (32/108)] were significantly higher than those in normal immune group (both P < 0.05). In terms of clinical symptoms, the proportion of fever in the immunocompromised group was significantly lower than that in the immune normal group [49.2% (30/61) vs. 66.7% (72/108), P < 0.05]. Neutrophil count (NEU) and neutrophil percentage (NEU%) in the immunocompromised group were significantly lower than those in the normal immune group. Lymphocyte percentage (LYM%), neutrophil/lymphocyte ratio (NLR), C-reactive protein (CRP), procalcitonin (PCT), APACHE II score, combined shock rate, incidence of immune paralysis, and mortality during hospitalization in the immunocompromised group were significantly higher than those in the normal immune group. Logistic regression analysis showed that NLR, CRP and PCT were risk factors for patients with immunocompromised sepsis (all P < 0.05). The above indicators were used as covariables to construct a Logistic regression equation, that was, Logit (P) = 0.025X₁+0.010X₂+0.013X₃-2.945, where X₁, X₂ and X₃ represent NLR, CRP and PCT respectively. Omnibus test and Hosmer-Lemeshow test show that the model fits well and has certain early warning value. CONCLUSIONS Patients with immunocompromised sepsis have more intense inflammatory response, with Gram-negative bacteria being the predominant pathogen, and a higher incidence of Gram-positive bacterial infections and multi-drug resistant infections. The severity of the disease, in-hospital mortality, the incidence of shock and the incidence of immune paralysis after sepsis were significantly higher. NLR, CRP and PCT were independent risk factors for sepsis in immunocompromised hosts. The regression equation constructed based on this may have early warning significance for patients with immunocompromised sepsis.
Humans ; Sepsis/immunology* ; Immunocompromised Host ; Retrospective Studies ; Risk Factors ; Intensive Care Units ; Logistic Models ; Male ; APACHE ; Female ; Middle Aged ; Aged

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

Objective:To compare the efficacy and clinical value of high-throughput sequencing(HTS)and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia(CML).Methods:A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain,and the relevant clinical data were collected for comparative analysis.Results:The proportion of total mutations and ≥ 2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing(P=0.01;P=0.046).≥ 2 mutations were detected in 22 cases,of which 5 cases(22.7％)had compound mutations.High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing.In 198 samples,25(12.6％)were low level mutations,33(16.7％)were high level mutations and 10(5.1％)were mixed high and low level mutations.In the analysis of related clinical factors,the total mutation rate and the low level mutation rate in the optimal period,failure period and warning period were gradually increased(total mutation rate,P=0.016;low level mutation rate,P=0.005).The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased(P=0.009).The mutation rate of patients who received first-and second-line treatment was significantly lower than that of patients who received third-or higher-line treatment(P=0.006).Analysis based on variant allele frequency(VAF)of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells.Conclusion:High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection,which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

Post-stroke cognitive impairment(PSCI)is a prevalent functional impairments following stroke that seriously affects patients'quality of life and daily activities.Studies indicate a close relationship between intestinal microflora dysbiosis and central nervous system diseases.Intestinal microflora profoundly impacts on human physiological health,contributing to the stability of nervous,metabolic and immune systems through regulation of the gut-brain axis.An increasing number of studies confirmed the important role of the gut microbiome-gut-brain axis in the occurrence and development of stroke and its associated PSCI,and regulation of microbiome-gut-brain could be potential target to treatment of PSCI.This review summarizes research progress on gut microbiome-gut-brain axis and PSCI to provide a reference for exploration of related mechanisms and clinical prevention and treatment strategies.

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.
Humans ; Male ; Female ; Adolescent ; Adult ; Middle Aged ; Herpesvirus 4, Human ; Epstein-Barr Virus Infections/complications* ; Rituximab/therapeutic use* ; Retrospective Studies ; Clinical Relevance ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Lymphoproliferative Disorders/drug therapy*

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
Pregnancy ; Female ; Humans ; Adult ; Hyperplasia ; Progestins ; Fertility Preservation ; Endometrial Neoplasms/pathology* ; Endometrial Hyperplasia/surgery* ; Treatment Outcome ; Precancerous Conditions ; Fertility ; Class I Phosphatidylinositol 3-Kinases ; Retrospective Studies