Objective: To analyze the unregistered treatment situation and its influencing factors among pulmonary tuberculosis patients in Quzhou City, Zhejiang Province from 2017 to 2023, so as to provide a basis for promoting the management of tuberculosis patients and optimizing disease prevention and control strategies. Methods: Data of pulmonary tuberculosis patients including demographic information, etiological results, and mortality status were collected through the China Disease Prevention and Control Information System Infectious Disease Reporting and Surveillance System and the Tuberculosis Management Information System. Pulmonary tuberculosis patients not matched in the Tuberculosis Management Information System were defined as unregistered treatment patients, and the unregistered treatment rate was analyzed. Factors affecting unregistered treatment among pulmonary tuberculosis patients were analyzed using a multivariable logistic regression model. Results: A total of 10 779 pulmonary tuberculosis patients were reported in Quzhou City from 2017 to 2023, including 7 700 males (71.44%) and 3 079 females (28.56%). There were 5 484 cases aged <65 years, accounting for 50.88%. Among them, 630 cases were unregistered treatment, with an unregistered treatment rate of 5.84% (95%CI: 5.42%-6.38%). Multivariable logistic regression analysis showed pulmonary tuberculosis patients aged ≥65 years (OR=1.829, 95%CI: 1.512-2.212) had a higher risk of being unregistered treatment than those aged <65 years; patients with non-local household registration (OR=5.710, 95%CI: 4.724-6.901) had a higher risk than local patients; and patients engaged in housework/unemployed (OR=2.001, 95%CI: 1.421-2.818) or other occupations (OR=2.396, 95%CI: 1.789-3.137) had a higher risk than farmers. The mortality of unregistered treatment pulmonary tuberculosis patients was higher than the registered treatment patients (26.67% vs. 5.02%),with a significantly elevated mortality risk (OR=7.147, 95%CI: 5.738-8.902). Conclusions The unregistered treatment rate among pulmonary tuberculosis patients was well controlled in Quzhou City from 2017 to 2023, but the elderly, patients with non-local household registration, and those engaged in housework/unemployed had a higher risk of unregistered treatment. It is recommended to improve medical and social security policies, strengthen health education on tuberculosis prevention, enhance treatment adherence, and reduce mortality risk.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective To isolate a Acinetobacter baumannii(Ab)phage from underground sewage,study its prop-erties,and to provide a theoretical basis for phage treatment of Ab infection.Methods Double-layer agar tech-nique was used to isolate phages by using Ab GY-6 as the host strain.Biological characterization and therapeutic effect of the phage was tested.Genetic information of the phage was analyzed.Results Ab phage Abgy202162 was isolated.Transmission electron microscopy(TEM)analysis showed that the morphology of Abgy202162 exhibited an icosahedral structure.Biological characteristic analysis showed that the optimal multiplicity of infection was 1,the latent period was 5 min,and the burst size was approximately 520 PFU per cell.In addition,Abgy202162 re-mained stable at different concentrations of chloroform,pH,and temperatures.Sodium dodecyl sulfate-polyacryl-amide gel electrophoresis(SDS-PAGE)analysis showed that it contained 10 proteins with molecular weights ran-ging from 15 to 100 ku.The double-stranded(ds)DNA genome of Abgy202162 consisted of 40 889 bp and its G+C content was 38.85％.It contained 47 open reading frames(ORFs),of which 26 had specific functions,but no virulence related genes or antibiotic resistance genes were found.Phylogenetic analysis showed that Abgy202162 was a new phage in the Autographiviridae family,Beijerinkvirinae subfamily,and Friunavirus genus.Abgy202162 showed the ability to prevent Ab infection in the Galleria mellonella in vivo model.Conclusion The phage Ab-gy202162 has strong environmental tolerance and high safety,indicating its potential as an antibiotic alternative used in the treatment of infections caused by Ab.

Objective:To investigate the impact of exogenous hypoxia-inducible factor 1α(HIF-1α)on glucose metabolism-related proteins and neurological function in the hippocampal CA1 region of rats with cerebral ischemia.Methods:Adult male SD rats were randomly assigned to four groups: sham operation group(Sham group), cerebral ischemia reperfusion group(CIR group), recombinant adenovirus empty vector intervention group(Ad group), and recombinant adenovirus HIF-1α gene intervention group(AdHIF-1α group), each consisting of 12 rats.A rat model of cerebral ischemia-reperfusion injury was induced using the modified suture method, and neurological deficits were assessed using the Longa method.In line with previous protocols, exogenous Ad and AdHIF-1α were introduced into the lateral ventricle of rats in the Ad and AdHIF-1α groups, respectively.After 28 days of observation, the animals were euthanized.Hippocampal tissue was collected for analysis, including Hematoxylin-eosin(HE)staining, terminal transferase labeling in situ(TUNEL)staining, and Nissl staining to evaluate pathological changes and neuronal survival in the hippocampal CA1 region.Western blot was performed to assess the expression levels of HIF-1α, glucose transporter 1(GLUT1), glucose transporter 3(GLUT3), and 6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3(PFKFB3)proteins in the hippocampal tissue.Results:Following 28 days of recombinant adenovirus HIF-1α gene therapy, rats in the AdHIF-1α group exhibited reduced neurological deficits compared to the CIR group( P<0.05).Histopathological analysis of nerve cells in the CA1 region of the hippocampus showed significant improvement, with an increase in the number of surviving nerve cells and a decrease in apoptotic cells( P<0.01).Western blot results indicated an upregulation of HIF-1α expression in the hippocampus of the CIR group compared to the Sham group, along with increased levels of glucose metabolism-related proteins(GLUT1, GLUT3, and PFKFB3)(all P<0.05).Furthermore, elevating HIF-1α expression through AdHIF-1α led to a further increase in the expression of glucose transporters(GLUT1, GLUT3, and PFKFB3)in the AdHIF-1α group, demonstrating statistically significant differences compared to the CIR group(all P<0.05).Notably, there were no statistically significant variances in the aforementioned parameters between the Ad group and the CIR group(all P>0.05). Conclusions:The AdHIF-1α gene has the potential to enhance neurological function, promote nerve cell survival, and decrease nerve cell apoptosis.This effect is likely achieved by increasing HIF-1α expression in the hippocampus, subsequently up-regulating GLUT1, GLUT3 and PFKFB3 expression, and ultimately improving glucose metabolism supply.Overall, this gene shows promise in protecting the brain.

In patients with periodontitis, due to problems of periodontal tissue infection as well as soft and hard tissues defects, it may lead to implant infection, gingival papilla loss, soft tissue recession and poor coordination with adjacent teeth. For such patients, periodontal infection should be actively controlled before dental implant therapy. In consideration of insufficient soft and hard tissues, alveolar ridge preservation and soft tissue augmentation procedure can be used to preserve or increase soft and hard tissues as much as possible. Multi-disciplinary treatment is often needed for occlusion problems and coordination with adjacent tooth. Periodontal maintenance treatment of implants and natural teeth is also necessary after implant therapy. This paper discussed these risk factors and strategies for prevention and control, in order to provide some clinical guidances for the implant treatment of periodontitis patients.

Objective:To analyze the effective and safety of endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (RAAA) at one tertiary center, and to improve the outcomes of RAAA under fast-track protocol.Methods:Nineteen cases of RAAA in the 940th Hospital of Joint Logistic Support Force of PLA from January 2014 to December 2020 were reviewed retrospectively. EVAR-fist strategy was employed from the emergency room to the operating room by using fast-track protocol. Preoperative management, anatomic characteristics, choice of anesthesia, operative procedures and postoperative complications were collected and analyzed. Abdominal compartment syndrome (ACS) and hospital mortality were paid special attention.Results:Nineteen cases were undergone EVAR procedures. The age was (73.4 ± 7.4) years old, and the AAA size was (67.8 ± 13.6) mm. Two cases underwent cardiopulmonary resuscitation at emergency department. General anesthesia was used in 13 patients and local anaesthesia in 6 patients. Successful stent graft deployment was achieved in all cases. The duration from emergency room to operating room was (84.8 ± 22.4) min. The hospital stay time was (9.7 ± 5.7) d. The hospital mortality was 5/19. The 5 deaths were reviewed: 3 died for multiple organ failure, 1 for irreversible shock, and 1 for ongoing bleeding.Conclusions:Excellent results were confirmed by using EVAR-first strategy for RAAA. The management of hemodynamically unstable state, standardized endovascular procedure, fast-track program and multidiscipline team collaboration were the very important determining factors for the implementation of EVAR. Focused efforts to reduce RAAA mortality are warranted.

Objective:To develop a deep learning model which can automatically and accurately detect osteoporotic vertebral compression fractures (OVCF) based on artificial intelligence.Methods:MRI images of 500 patients diagnosed with OVCF at The First People＇s Hospital of Guangzhou from January 2019 to October 2021 were collected retrospectively. There were 396 males and 204 females, with an age of (74.5±6.0) years. The T value of bone mineral density was -2.9±0.8. The fracture segments were L1 in 128 cases, L2 in 113 cases, L3 in 109 cases, L4 in 115 cases, and L5 in 108 cases. The multimodal layered converged network was used to train, test, and verify the robustness and generalization ability of a deep learning model based on MRI images of OVCF. The grad-cam was applied to visualize the results. The diagnostic value of the model for OVCF was assessed by comparing the diagnoses between the artificial intelligence model and 2 senior spinal surgeons on the MRI images of 30 OVCF patients randomized from the 500 ones.Results:Of the precise auxiliary diagnosis model for OVCF based on MRI images, the diagnostic accuracy was 96.7%, the sensitivity 93.5%, the specificity 88.9%, the positive predictive value 100.0%, and the negative predictive value 86.6%, all significantly higher than those of the 2 senior spinal surgeons (70.0%, 72.7%, 28.6%, 82.1%, and 28.6%) ( P<0.05). Conclusion:The present study has successfully established a deep learning model which can automatically and accurately diagnose OVCF based on MRI images, showing a high diagnostic efficiency than human spinal surgeons.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To investigate whether GIV , a coiled helix structural domain protein containing 88A , has an effect on the neuroinflammatory response in a model of cerebral ischemia⁃reperfusion injury. Methods: A middle cerebral artery embolization⁃reperfusion model (MACO/R) and an oxygen glucose deprivation/reoxygenation model ( OGD 6 h + R 24 h) of BV2 microglia were constructed in C57BL/6 mice , and the area of cerebral infarction was detected by TTC staining; the Longa neurobiological score was used to evaluate the degree of neurological deficit in mice ; ELISA was used to detect the release of IL⁃6 and TNF⁃α in the supernatant of peripheral blood and cell cultures , and Western blot was used to detect the protein expression of GIV , TREM2 and TLR4 in the cortical area around the infarct foci in mice ; different concentrations of lipopolysaccharide (LPS , 1 , 5 , 10 μg/ml) were used to stimulate BV2 cells for 24 h to establish a neuroinflammation model , qRT⁃PCR was performed to detect the mRNA levels of IL⁃6 , TNF⁃α and IL⁃1β , and Western blot was used to detect the expression of GIV ; OGD/R culture treatment was performed after knocking down the expression of GIV gene using siRNA interference technique ;ELISA was performed to detect the release concentration of IL⁃6 and TNF⁃α in cell culture medium supernatant;protein immunoblotting was performed to detect the knockdown efficiency of GIV. Results : Both the successfully constructed MCAO/R and OGD/R models activated the neuroinflammatory response and induced a decrease in protein expression of GIV ; MCAO/R induced increased concentrations of IL⁃6 and TNF⁃α release in peripheral blood of mice and promoted the protein expression of TREM2 and TLR4 ; LPS activated IL⁃6 , IL⁃1β and TNF⁃α expression in BV2 cells , but did not affect GIV expression ; siRNA interference with GIV gene expression further in creased the expression of inflammatory factors IL⁃6 and TNF⁃α . Conclusion The GIV gene may be characteristically involved in regulating the neuroinflammatory response induced by cerebral ischemia⁃reperfusion injury , and it may be a potential therapeutic target for cerebral ischemia⁃reperfusion injury.

Objective : To explore the role of Argonaute ( Ago) gene and RNA⁃Dependent RNA Polymerase (RDRP) gene of Aspergillus flavus in the growth and development about the RNAi mechanism . Methods : A. flavus Ago1 , Ago2 , RDRP1 , RDRP3 gene mutant strains were constructed by homologous recombination . The growth and development of the mutant strains were observed on potato dextrose agar(PDA) + uracil uridine (UU) medium inoculated with 3 μl 106 CFU/mL spores . 200 , 400 μg cell wall pressure agent conidored ( CR) , 0. 8 mol/L , 1 . 6 mol/L osmotic pressure agent NaCl , 2 mmol/L , 4 mmol/L oxidative pressure agent hydrogen peroxide (H2 O2 ) and 0. 01% , 0. 02% genomic damage agent methyl mesylate (MMS) were added to the Yeast extract Glucose Minimum (YGM) + UU medium to analyze the stress response of the mutant strains . Results : A. flavus mutant strains about ΔAgo1 , ΔAgo2 , ΔRDRP1 , ΔRDRP3 were successfully constructed and its growth and development were normal . The ΔAgo1 and ΔAgo2 strains reduced the stress effects on cell wall and osmotic pressure compared to the control . Ago1 gene deletion reduced the effect of H2 O2 , and conversely RDRP3 gene deletion increased the inhibition of H2 O2 . The Ago2 and RDRP1 strains reduced the effect on genetic damage agent . In addition , ΔRDRP1 increased the effect of osmotic stress . Conclusion The Ago1 , Ago2 , RDRP1 and RDRP3 genes of A. flavus are not in⁃ volved in the regulation of growth rate and asexual reproduction and can participate in the regulating of the host stress response to the environment .