Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

OBJECTIVE: To explore the early clinical outcomes of 3D printed individualised customised prostheses for in hip revision in patients with combined severe bone defects. METHODS: Twenty-two patients from January 2021 to May 2023 underwent hip revision using 3D printed personalised customised prostheses were retrospective analyzed, including 10 males and 12 females, age 28 to 78 with a mean of (58.9±12.8) years old. All of patients were combined with severe bone defects (Parprosky type Ⅲ). Among of them, 9 patients had periprosthetic infections and 13 patients had aseptic prosthesis loosening. All patients were treated with a 3D printed personalised prosthesis protocol, patients with the periprosthetic infection received a second stage revision after infection control. The operation time, preoperative waiting time, intraoperative and postoperative complications were recorded, and the clinical efficacy were evaluated at the final follow-up using the visual analogue scale (VAS) for pain, the Harris hip score. RESULTS: One patient was lost to follow-up and the remaining 21 patients were followed up for 10 to 15 with a mean of (12.91±1.44) months after surgery. All patients completed surgery as planned, with an operative time of 135 to 390 with a mean of (165.4±39.3) minutes and a preoperative waiting time of 7 to 16 with a mean of (10.5±3.3) days. Regarding patient complications:one patient had a severe intraoperative periprosthetic femoral fracture due to the combination of severe osteoporosis; one patient had an intraoperative greater trochanteric femur fracture. At the latest follow-up, all patients had good position of the custom-made prosthesis and no loosening of the prosthesis;all patients had good wound healing and no local redness or swelling. The total Harris score at the final follow-up (85.86±7.04) was significantly improved compared to the preoperative (44.86±2.36), P<0.001. The VAS at the last follow-up (2.19±0.87) was significantly improved compared with preoperative (7.41±0.96), P<0.001. CONCLUSION The clinical efficacy of 3D-printed personalised customised prosthesis in combined severe bone defect hip revision is satisfactory, but due to the increased preoperative waiting time of the patients and certain risks, certain indications should be mastered when applying in the clinic.
Humans ; Male ; Female ; Printing, Three-Dimensional ; Middle Aged ; Aged ; Adult ; Retrospective Studies ; Hip Prosthesis ; Arthroplasty, Replacement, Hip ; Reoperation ; Prosthesis Design ; Treatment Outcome

OBJECTIVE: Investigation on the clinical application of HURWA robot and Smith & Nephew Cori robot in total knee arthroplasty(TKA). METHODS: A retrospective analysis was performed on 84 patients with knee osteoarthritis who underwent robotic-assisted TKA (RATKA) between June 2023 and March 2025. According to the different robotic systems used, the patients were divided into the domestic HUARUN robotic-assisted total knee arthroplasty group (HRATKA group) and the Smith & Nephew Cori robotic-assisted total knee arthroplasty group (CRATKA group). There were 42 patients in the HRATKA group, including 16 males and 26 females; the age ranged from 56 to 73 years old, with an average of (64.70±8.30) years old;the body mass index (BMI) was (25.10±2.30) kg·m^-2;21 cases were on the right side and 21 cases on the left side;in terms of Kellgren-Lawrence(K-L) classification, there were 15 cases of Grade Ⅲ and 27 cases of Grade Ⅳ;the disease duration ranged from 3 to 25 years, with an average of (15.5±7.5) years. The CRATKA group also included 42 patients, with 14 males and 28 females;the age ranged from 58 to 74 years old, with an average of (65.60±7.50) years old;the BMI was (24.50±2.70) kg·m^-2; 20 cases were on the right side and 22 cases on the left side;regarding K-L classification, there were 11 cases of Grade Ⅲ and 31 cases of Grade Ⅳ;the disease duration ranged from 2 to 26 years, with an average of (16.5±8.8) years. Collect general data of all patients, including age, gender, height, weight, surgical site, K-L classification, incision length, and operation time. To evaluate prosthesis position, compare the frontal tibia component (FTC) angle, lateral femoral component (LFC) angle, lateral tibia component (LTC) angle, and frontal femoral component angle between the two groups of patients after surgery. Measure the deviation of the hip-knee-ankle (HKA) angle to assess lower limb alignment. Additionally, compare the following indicators between the two groups:Knee Society Score (KSS), Visual Analogue Scale (VAS) for pain, knee range of motion (ROM), hemoglobin (HB) level, hematocrit (HCT) level, complication rate, and in-hospital satisfaction. RESULTS: All patients successfully completed the surgery as scheduled, and all were followed up after the operation. The follow-up period ranged from 5 to 17 months with an average of (11.2±6.1) months. There were 4 cases of venous thrombosis in the HRATKA group and 3 cases in the CRATKA group;each group had 2 cases of wound exudation. No mechanical-related complications, pulmonary embolism, or other severe complications occurred. Comparison of the incision length and hospital stay between the HRATKA group and the CRATKA group showed no statistically significant difference (P>0.05). The operation time in the HRATKA group was (96.80±7.10) minutes, which was longer than that in the CRATKA group (90.10±8.80) minutes, and the difference was statistically significant (P<0.05). In the HRATKA group, the HKA angle was (178.93±1.11) degree, the FFC angle was (89.00±0.91)°, and the LFC angle was (7.31±2.17) degree;the corresponding values in the CRATKA group were (178.05±1.34)°, (87.88±1.74)°, and (10.60±2.84) degree respectively. The differences in these three indicators between the two groups were all statistically significant (P<0.05). However, there were no statistically significant differences in the FTC angle or LTC angle between the two groups (P>0.05). There was also no statistically significant difference in the total perioperative blood loss between the two groups (P>0.05). At 3 days after surgery, the VAS score for movement in the HRATKA group (5.95±1.45) points was higher than that in the CRATKA group (4.50±0.97) points, with a statistically significant difference (P<0.05);at 90 days after surgery, there was no statistically significant difference in the movement VAS score between the two groups (P>0.05). Additionally, no statistically significant differences were observed between the two groups in the KSS, ROM at 3 and 90 days after surgery, or satisfaction degree during hospitalization (all P>0.05). CONCLUSION The domestic HURWA robot demonstrates excellent performance in osteotomy efficiency and lower limb alignment recovery. The Smith & Nephew Cori robot has a significant advantage in soft tissue assessment and joint stability optimization. Both robotic systems offer high-quality surgical treatments that significantly improve short-term knee function.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/instrumentation* ; Aged ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures/methods* ; Osteoarthritis, Knee/surgery*

We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve

OBJECTIVE: To investigate the expression of CD19/CD73 in chronic lymphocytic leukemia (CLL) and its correlation with clinical features. METHODS: The clinical data of 60 CLL patients and 40 healthy volunteers (control group) from January 2022 to November 2023 were retrospectively analyzed. The levels of CD19 and CD73 in peripheral blood of CLL patients were measured by flow cytometry. Kaplan-Meier method was used for survival analysis. RESULTS: The hemoglobin (Hb) and CD19/CD73 levels in CLL group were significantly lower than those in control group, while CD19, CD73 and β₂-MG were significantly higher (all P <0.001). According to ROC curve analysis, the AUC value of CD19/CD73 for CLL diagnosis was 0.980 (95%CI : 0.949-1.000, P <0.05), the specificity was 92.50%, and the sensitivity was 98.30%. The CD19/CD73 level of CLL patients with splenomegaly was significantly lower than those without splenomegaly (P <0.01). There was no significant correlation between CD19/CD73 and Hb in CLL patients ( r =0.056, P >0.05). CD19/CD73 was positively correlated with β₂-MG ( r =0.837, 95%CI : 0.740 2-0.899 6, P <0.01). According to the median value (12.84) of CD19/CD73, the patients were divided into high and low expression groups. Kaplan-Meier survival analysis showed that the overall survival rate and progression-free survival rate at 18^th month in the low expression group were 87.08% and 93.25%, while those in the high expression group were 96.41% and 99.90%, respectively (both P <0.05). CONCLUSION The level of CD19/CD73 is low in CLL patients, which can be used as an auxiliary index for clinical diagnosis of CLL. CD19/CD73 is closely related to splenomegaly in CLL patients. Low expression of CD19/CD73 predicts poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/metabolism* ; 5'-Nucleotidase/metabolism* ; Antigens, CD19/metabolism* ; Retrospective Studies ; Male ; Female ; Prognosis ; Middle Aged ; Aged ; Adult ; GPI-Linked Proteins

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

The Ebola virus (EBOV), a member of the Filoviridae family, is a highly pathogenic agent responsible for severe hemorrhagic fever in humans. Understanding the molecular mechanisms governing its replication is critical for developing effective antiviral strategies. VP35-TurboID immunosuppression coupled with quantitative mass spectrometry identified Septin9, the host GTP-binding protein which played a role in cytoskeletal regulation, as a novel interactor of VP35. Western blotting and Far-Western blotting confirmed the direct interaction and demonstrated that the C-terminal region of VP35 was the critical binding domain. Functionally, EBOV replication as well as the formation of viral inclusion bodies (VIBs) was demonstrated to be significantly suppressed by Septin9 knockdown and depletion, as shown by the EBOV minigenome (EBOV MG) and the transcription- and replication-competent virus-like particles (trVLPs) system. This study reveals that VP35 engages in a specific interaction with the GTP-binding protein Septin9, thereby impeding EBOV replication through the disruption of inclusion bodies. The overarching objective of this study is to significantly enhance our understanding about the pathogenic mechanism of EBOV and offer a robust theoretical foundation and solid empirical support for the formulation of innovative therapeutic strategies against EBOV.
Virus Replication/physiology* ; Septins/physiology* ; Humans ; Ebolavirus/physiology* ; Inclusion Bodies, Viral/metabolism* ; Viral Regulatory and Accessory Proteins/metabolism* ; Hemorrhagic Fever, Ebola/virology*

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.