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.

Objective:To evaluate the efficacy and safety of lenvatinib combined with camrelizumab as the second-line treatment for advanced intrahepatic cholangiocarcinoma (ICC).Methods:The clinical data of patients with advanced ICC undergoing the second-line treatment of lenvatinib combined with camrelizumab in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from June 2021 to June 2022 were screened and analyzed. A total of 12 patients were enrolled, including seven males and five females, aged (67.5±8.6) years. Response evaluation criteria in solid tumor 1.1 was used to evaluate the efficacy of treatment. The safety assessment adopts the Adverse Event Evaluation Standard 5.0. Kaplan-Meier method was conducted to plot survival curves.Results:Among the 12 patients (after 1-7 cycles of immune and targeted therapy), three achieved partial response, four achieved stable disease, and five were defined as progression disease. Adverse events of different degrees occurred in seven cases, among which three patients had adverse events of grade ≥ 3: one with hypertension, which was managed after antihypertensive and symptomatic treatment; one with elevated serum total bilirubin, which was improved after reducing the dose of lenvatinib; one with liver dysfunction, which was considered as immune-related liver toxicity and alleviated after discontinuing camrelizumab. The 1-month, 3-month, and 6-month survival rates and progression-free survival rates of the patients were 100.0%, 91.7%, 66.7%, and 83.3%, 41.7%, and 25.0%, respectively. The median overall survival of patients was 14.7 months (95% CI: 9.2-21.2) and the median time to progression was 8.0 months (95% CI: 4.1-11.9). Conclusion:Combination of lenvatinib and camrelizumab could bring survival benefits with controllable adverse events as the second-line treatment of patients with advanced ICC.

Objective:To investigate the effect of high-dose vitamin B6 on stress-induced liver cell death in rats with severe trauma and its possible mechanism.Methods:Thirty-two male SD rats were selected and divided into sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group by using a random number table, with 8 rats in each group. Rat models of severe trauma were established by inducing abdominal wall injury, bilateral femoral fractures, unilateral cranial injury, and withdrawal of 4 ml blood from the femoral artery. The sham surgery+B6 group and trauma+B6 group were treated with saline solution plus high-dose vitamin B6, while the sham surgery group and trauma group with infusion of saline solution only. At 36 hours after injury, rat liver tissues were collected for the following experiments: (1) the genes differentially expressed in the liver tissues of the rats of the trauma group and the trauma+B6 group were screened with next-generation sequencing, followed by an analysis of the possible involvement of cell death pathways; (2) validation was conducted to ascertain whether high-dose vitamin B6 could influence various cell death pathways in the liver cells in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group: apoptosis was confirmed through terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining; necroptosis was verified by mixed lineage kinase domain-like protein (MLKL) immunohistochemical staining; autophagy was examined via transmission electron microscopy; ferroptosis was confirmed by detecting oxidative malondialdehyde (MDA) levels, oxidized glutathione levels, Prussian blue staining with diaminobenzidine (DAB) enhancement, transmission electron microscopy, and immunohistochemical staining for acyl-CoA synthetase long-chain family member 4 (ACSL4); (3) Biological information analyses [Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Enrichment analysis (GSEA)] were performed for biological processes and signaling pathways represented by liver tissue sequencing results of rats between the trauma group and the trauma+B6 group.Results:(1) In the liver tissues of rats, there were 344 significantly differentially expressed genes between the trauma group and trauma+B6 group, comprising 137 upregulated genes and 207 downregulated genes, of which 18 genes were associated with apoptosis, autophagy, necroptosis, ferroptosis, and pyroptosis. (2) No significant differences were found in TUNEL staining among the sham surgery group, sham surgery+B6 group, trauma group or trauma+B6 group; MLKL protein expression levels in the liver tissues after trauma were improved, of which the trauma+B6 group was lower than that of the trauma group; Electron microscopy showed that autophagic activity in the liver cells were significantly increased after trauma, which was significantly lower of the trauma+B6 group than that of the trauma group; MDA levels in the rat liver tissues were (0.20±0.05)nmol/mg, (0.17±0.07)nmol/mg, (0.69±0.11)nmol/mg and (0.52±0.07)nmol/mg in the sham surgery group, sham surgery+B6 group, trauma group, and trauma+B6 group respectively ( P<0.01), with the trauma group having the highest MDA levels and trauma+B6 group having lower MDA levels than the trauma group; Oxidized glutathione levels in the liver tissues of the four groups were (11.75±2.09)μmol/g, (11.69±1.66)μmol/g, (19.75±3.40)μmol/g, and (14.51±1.46)μmol/g respectively ( P<0.01), with the trauma group having the highest levels and trauma+B6 group having lower levels than the trauma group; Significantly increased iron deposition was observed in the liver tissues after trauma, with lower iron deposition in trauma+B6 group than the trauma group; Electron microscopy revealed significantly lower mitochondrial membrane density in the trauma+B6 group compared to the trauma group. ACSL4 protein expression level was lower in the trauma+B6 group compared to the trauma group; (3) GO, KEGG and GSEA enrichment analyses suggested that high-dose vitamin B6 may enhance cholesterol synthesis metabolism in the liver cells and alleviate oxidative stress to reduce liver cell damage and restore normal liver cell function after trauma. Conclusions:High-dose vitamin B6 attenuates stress-induced liver injury in rats with severe trauma by inhibiting the progression of necroptosis, autophagy and ferroptosis. Its molecular mechanism may be associated with enhanced hepatic cholesterol synthesis metabolism and alleviation of oxidative stress in the liver cells.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

Objective To investigate the clinical features of malignant tumor-related pyogenic liver abscess (PLA), and to provide a basis for early judgment of disease progression and timely and effective treatment. Methods A retrospective analysis was performed for the clinical data of 371 patients with PLA who were admitted to the Second Affiliated of Air Force Medical University, from March 2005 to July 2018, among whom 34 patients with malignant tumor-related PLA were enrolled as tumor group, and after matching for time and at a ratio of 1∶2, 70 patients without malignant tumor-related PLA were enrolled as non-tumor group. Clinical features were compared between the two groups. The group t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results In the tumor group, there were 22 patients with hepatobiliary tumor (64.7%), 7 patients with gastrointestinal tumor (20.6%), and 5 patients with non-gastrointestinal tumor (14.7%). Compared with the non-tumor group, the tumor group had a significantly higher proportion of patients with a history of abdominal surgery (44.1% vs 7.1%, χ 2 =20.142, P < 0.05), liver cirrhosis (26.5% vs 7.1%, χ 2 =7.338, P < 0.05), or an Acute Physiology and Chronic Health Evaluation Ⅱ score of > 16 (44.1% vs 15.7%, χ 2 =9.846, P =0.002). Compared with the non-tumor group in terms of laboratory examination, the tumor group had a significantly lower level of albumin [(27.2±5.2) g/L vs (30.8±2.6) g/L, t =-3.131, P =0.002] and a significantly higher level of total bilirubin [54(13~313) μmol/L vs 33(7~96) μmol/L, U =1 816.0, P < 0.001]. Escherichia coli was the main pathogen in the tumor group (23.5%), while Klebsiella pneumonia was the main pathogen in the non-tumor group (23.5%), and compared with the non-tumor group, the tumor group had a significantly higher proportion of patients infected with more than two types of bacteria (11.8% vs 2.8%). Radiological examination showed that the tumor group had a significantly higher proportion of patients with multiple abscesses than the non-tumor group (47.1% vs 24.3%, χ 2 =5.479, P =0.019). Compared with the non-tumor group, the tumor group had a significantly longer mean length of hospital stay ( U =1 728.5, P < 0.001) and a significantly higher treatment failure rate ( P =0.005). Conclusion Patients with malignant tumor-related PLA often have hepatobiliary tumor, with Escherichia coli as the main pathogen. Abscesses at multiple sites are common, and patients tend to have a poor prognosis. Appropriate antibiotics combined with percutaneous drainage should be used in clinical practice, and for the high-risk population, the threshold for surgical intervention can be lowered to reduce mortality.

Delayed endolymphatic hydrops （DEH） is a rare disease that causes vertigo and is often misdiagnosed as other vertigo diseases. This article reports on a patient with vertigo who was easily misdiagnosed. The patient was a middle ear cholesteatoma complicated by labyrinthine fistula （LF）; however, his vertigo was episodic vertigo, which could not be explained solely by LF causing labyrinthitis. The possibility of endolymphatic hydrops was suspected, which was confirmed by inner ear magnetic resonance gadolinium imaging. This is the first reported case of middle ear cholesteatoma complicated by LF and DEH. The patient underwent surgical resection of the cholesteatoma and three semicircular canal obstructions at the same time. During two years postoperative follow-up, the patient did not experience a recurrence of vertigo. When diagnosing vertigo diseases, a careful history of vertigo is of utmost importance.
Humans ; Endolymphatic Hydrops/diagnosis* ; Cholesteatoma, Middle Ear/complications* ; Vertigo/complications* ; Labyrinth Diseases/complications* ; Magnetic Resonance Imaging/adverse effects* ; Semicircular Canals

AIM:To explore the effect and mechanism of hydrogen sulfide(H2S)on autophagy and angiogene-sis in skin wound of diabetic rats.METHODS:Among 36 healthy 8-week-old male Sprague-Dawley rats,12 rats were se-lected as control group,and the remaining rats were intraperitoneally injected with streptozotocin(STZ)to induce diabetic model and were randomly divided into diabetes mellitus(DM)group and NaHS(H2S donor)intervention(DM+NaHS)group,with 12 rats in each group.A skin trauma model was established by excising the skin of the back of rats in each group.The rats in DM+NaHS group were intraperitoneally injected with NaHS(56 μmol/kg),and the rats in control and DM groups were daily received the same volume of normal saline for 21 consecutive days.The healing of skin wound was measured on days 0,7,14 and 21 after operation.On the 21st day after surgery,the content of H2S in skin tissues was de-tected by C-7Az fluorescent probe,and the morphological changes and angiogenesis of wound tissues were observed by HE staining.The expression of CD31 was detected by immunofluorescence staining,and endothelial autophagy was detected by double staining of CD31 and beclin-1.The protein levels of cystathionine γ-lyase(CSE),CD31,microtubule-associated protein 1 light chain 3(LC3),beclin-1,P62,Bcl-2,Bax,phosphatidylinositol 3-kinase(PI3K),protein kinase B(PKB/Akt)and mammalian target of rapamycin(mTOR)in wound tissues were determined by Western blot.Caspase-3 and propidium iodide(PI)staining was used to detect cell apoptosis,and apoptosis of vascular endothelial cells was deter-mined with CD31 and TUNEL double immunofluorescence staining.RESULTS:Compared with DM group,the wound healing rate,H2S content and CSE protein expression were significantly increased in DM+NaHS group(P＜0.01),but still lower than those in control group(P＜0.01).HE staining showed that the wound surface in DM group was thin and wide,with few capillary,while that in DM+NaHS group was thicker with lots of capillary and wound width was reduced.Com-pared with DM group,CD31 expression was markedly increased(P＜0.01),the fluorescence intensity of caspase-3 and PI was significantly decreased(P＜0.01),and CD31+/beclin-1+ as well as CD31+/TUNEL+ cells were decreased(P＜0.01)in DM+NaHS group.Western blot analysis showed that compared with DM group,the levels of beclin-1,Bax and LC3-Ⅱ/LC3-Ⅰ were significantly decreased(P＜0.01),while the levels of P62 and Bcl-2,as well as ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR were significantly increased(P＜0.01)in DM+NaHS group.CONCLUSION:H2S can promote skin wound healing,which may be related to activation of PI3K/Akt/mTOR signaling pathway,inhibition of endothelial au-tophagy and apoptosis,and promotion of angiogenesis in diabetic rats.

Objective:To investigate the feasibility and potential of fluorescent cholecystic bile duct visualization with direct intravenous injection of indocyanine green(ICG) in obese patients undergoing laparoscopic cholecystectomy(LC).Methods:The clinical data of 132 patients with LC combined with obesity admitted to the Department of Hepatobiliary and Pancreatic Surgery of the Second People′s Hospital of Changzhou City, affiliated to Nanjing Medical University, from January 2023 to July 2023 were retrospectively analyzed. They were divided into fluorescence group( n=65) and control group( n=67) according to whether indocyanine green fluorescence navigation was used or not. There were 50 males and 82 females, and all the enrolled patients body mass index≥28 kg/m 2. Two groups identify the time of the three tubes, intraoperative bleeding, operation time, postoperative hospitalization time, white blood cell count(WBC), C-reactive protein(CRP), alanine aminotransferase(ALT), gamma-glutamyl transferase(GGT), and postoperative follow-up in the fluorescent and control groups were counted respectively. Measurement data with skewed distribution were expressed as M( Q1, Q3), and intergroup comparisons were performed using the Mann-Whitney U test; counting data were described by frequency(rate), and intergroup comparisons were made by applying the chi-square test, Fisher′s exact probability method, and chi-square corrected test according to the difference in the minimum frequency. Results:Surgery was successfully completed in both groups. Preoperative inflammatory indicators and liver function levels were also not statistically significant( P>0.05). The time to identify the three tubes, operation time, intraoperative bleeding, and postoperative hospitalization in the fluorescence group were 18.00(13.50, 20.00) min, 40.00(30.00, 50.00) min, 5.00(5.00, 10.00) mL, and 2.00(1.50, 3.00) d, and in the control group were 32.00(25.00, 45.00) min, 65.00(50.00, 85.00) min, 41.00(41.00, 46.00) mL, and 4.00(3.00, 5.00) d. The differences between the two groups were statistically significant( P<0.05). The postoperative leukocyte count, postoperative CRP, and postoperative GGT were 9.15(7.10, 11.75)×10 9/L, 7.19(3.22, 20.00) mg/L, and 34.0(20.0, 49.0) U/L in the fluorescence group, and 13.05(11.02, 15.59)×10 9/L, and 18.78(12.90, 32.95) mg/L in the control group, respectively, 82.5(68.5, 114.5) U/L, and the differences between the two groups were statistically significant ( P<0.05). None of the patients showed abdominal pain, abnormal liver function and hepatobiliary ultrasound in the follow-up findings within 2 months after surgery. Conclusion:The effect of obesity, a factor that interferes with ICG fluorescence, is extremely limited, and ICG fluorescence cholangiography is a useful technique in the obese population that not only improves the efficiency of the procedure, but also increases intraoperative safety, with results superior to those of conventional laparoscopic cholecystectomy.

Objective:To summarize the experience of ambulance medical support in the 19th Hangzhou Asian Games, and provide reference for the ambulance medical support work of large-scale sports events in the future.Methods:According to the actual situation of the Asian Games, the objectives of the medical support were determined according to the principles of highlighting the key points and overall consideration. All kinds of ambulances were allocated according to the principles of combining dynamic and static and regional linkage. The ambulance support was divided into the event side and the city side,with the regional security vehicle as the supplement of the event side and the guarantee of the city side, the implementation of "one pavilion one policy", "one game one policy", "one place one policy" and "one vehicle one plan", and the interconnection of medical points (rooms), designated hospitals, management and command personnel and ambulances were realized through the Asian Games Intelligent Emergency Medical Support Syetem (EMSS).Results:Between September 16, 2023, 08:00, and October 9, 2023, 08:00, a total of 207 ambulances were deployed during the 19th Hangzhou Asian Games. Of these, 88 (42.5%) were at competition venues, 11 (5.3%) at training venues, 30 (14.5%) at non-competition venues, and 78 (37.7%) were regional support vehicles. Among them, 20 venue ambulances participated in regional support tasks during idle times. Ambulances transported patients from event sites 345 times, with the highest number of transports occurring at competition venues (187 times) and the fewest in the assisting city of Huzhou (6 times). The highest ambulance utilization rate was 70.5% at competition venues, while training venues, non-competition venues, and regional support ambulances had utilization rates of 45.5%, 53.3%, and 42.3%, respectively. The median age of transported individuals was 26 (21, 36), with a majority being male (59.1%). Athletes comprised 52.5% of transports, while staff and spectators accounted for 39.7% and 7.8%, respectively. Joint injuries were the most common condition among transported individuals, totaling 58 cases (16.8%). Regional support ambulances participated in 75 transfers and replacements, with 17 (22.7%) transfers and 58 (77.3%) replacements.Conclusions:This study confirms the feasibility and efficiency of the Asian Games' ambulance support plan, highlighting the crucial role of EMSS. The study suggests the need to strengthen medical support for staff, in addition to athletes.

Objective: To analyze the epidemiological and clinical characteristics of pulmonary tuberculosis patients complicated by diabetes mellitus (PTB-DM), so as to provide insights into PTB-DM control. Methods: The data pertaining to PTB cases in Quzhou City from 2016 to 2020 were extracted from Tuberculosis Information Management System of Chinese Disease Prevention and Control Information System. The demographic features, diagnosis and treatment of PTB-DM patients were descriptively analyzed, and compared with PTB patients. Results: The incidence of PTB-DM was 6.79/105 to 9.27/105 in Quzhou City from 2016 to 2020, with an annual increase rate of 8.09%. Among all PTB-DM patients, there were 674 men (76.94%), 620 cases at ages of 60 years and older (70.78%), 564 cases living in urban areas (64.38%), 619 farmers (70.66%), 537 cases with delay in healthcare-seeking (61.30%), 802 treatment-naïve cases (91.55%), 547 cases positive for pathogenic tests (62.44%), 11 cases with rifampicin resistance (1.26%), 695 cases with negative conversion of sputum smears 2 months post-treatment (79.34%), and 783 cases with successful treatment (89.38%). The proportions of men, ages of 60 years and older, living in urban areas, farmers, delay in healthcare-seeking, positive pathogenic tests and rifampicin resistance were significantly higher among PTB-DM patients than among PTB patients, and the negative conversion rate of sputum smears 2 months post-treatment was significantly lower among PTB-DM patients than among PTB patients (all P<0.05). Conclusions The incidence of PTB-DM increased year by year in Quzhou City from 2016 to 2020, and PTB-DM cases were predominantly found among elderly men. The proportion of delay in healthcare-seeking, positive pathogenic tests and rifampicin resistance was higher among PTB-DM patients than among PTB patients.