Objective: To analyze the process of handling a pulmonary tuberculosis(TB) outbreak among senior high school students in a boarding school in Chongqing, as well as to investigate the underlying causes of the outbreak, so as to provide evidence to inform TB prevention and control strategies in school settings. Methods: From November 2023 to April 2024, an epidemiological investigation was conducted into the TB outbreak in a grade 12 class from a boarding high school. Suspected cases were screened using symptom screening, tuberculin skin test (TST), and chest X-ray examinations. Confirmed cases underwent individual epidemiological interviews and sputum culture; Cultured positive mycobacterial strains were subjected to whole genome sequencing after identification as Mycobacterium tuberculosis. Results: A total of 10 active pulmonary TB cases were identified, all from the same class, yielding a student attack rate of 16.67%. Three isolates were culture positive, as well as all strains were of L2 type，and the WGS analysis of the strains suggested a common transmission chain. Excluding the index case, four additional cases were detected through symptom driven health care visits. Notably, 70% of patients presented with "chest tightness and chest pain" symptoms, and 50% had "cough" symptoms,but none were detected during morning health checks or tracking of absences due to illness. A total of 326 contacts were identified and underwent three rounds of screening and one follow up examination. In the initial screening, 35 close contacts from the same class showed strong TST positivity, corresponding to a strong positivity rate of 55.56%, significantly higher than the 20.76% observed among casual contacts ( χ 2=29.80, P <0.01). Among the 35 strongly TST positivvity close contacts and five individuals with moderate TST positivity whose induration had increased by ≥10 mm over two years, none received timely preventive treatment initially; five of them were subsequently diagnosed with active TB within three months. Following this, 25 individuals initiated preventive therapy, resulting in a preventive treatment initiation rate of 62.50%. Among TST negative classmates who converted to strong positivity on repeat TST testing at three months, 75.00% started preventive treatment, but only 22.22% completed the full course. Conclusion Inadequate implementation of morning health checks and cause tracking for absenteeism due to illness, poorly standardized screening procedures, and delayed preventive treatment may have been key factors contributing to the spread of the outbreak.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To investigate the expression and clinical significance of urinary C-X-C motif chemokine ligand 10(CXCL10)and C-X-C motif chemokine ligand 16(CXCL16)in patients with idiopathic membranous nephropathy(IMN).Methods:A total of 131 patients with IMN(IMN group)who were treated in Zhejiang Provincial Corps Hospital of the Chinese People's Armed Police Force from December 2020 to June 2022 were prospectively selected,131 healthy volunteers(control group)who underwent physical examination during the same period were selected.Patients with IMN were divided into stage Ⅰ group(25 cases),stage Ⅱ group(68 cases),stage Ⅲ group(22 cases)and stage Ⅳ group(16 cases)according to pathological staging,patients were divided into non-remission group(33 cases)and remission group(98 cases)based on the therapeutic efficacy after a 2-year follow-up.Urinary CXCL10 and CXCL16 levels were measured by enzyme-linked immunosorbent assay.Clinical data of patients with IMN were collected,The relationship between urinary CXCL10,CXCL16 levels and pathological staging in patients with IMN was analysied by Spearman/pearson correlation.Multivariate logistic regression analysis influencing factors on non-remission treatment in patients with IMN,and receiver operating characteristic(ROC)curves were used to assess the predictive value Of urinary CXCL10,CXCL16 levels for non-remission treatment in patients with IMN.Results:Urinary CXCL10 and CXCL16 levels in the IMN group were significantly higher than those in the control group(P＜0.05).Urinary CXCL10 and CXCL16 levels were the highest in stage Ⅳ group,urinary CXCL10 and CXCL16 levels in stage Ⅲ group were higher than those in stage Ⅱ group and stage Ⅰ group,and urinary CXCL10 and CXCL16 levels in stage Ⅱ group were higher than those in stage Ⅰ group(P＜0.05).Urinary CXCL10 and CXCL16 levels in patients with IMN were positively correlated with pathological staging,urinary CXCL10 were positively correlated with CXCL16(P＜0.05).Urinary CXCL10 and CXCL16 in non-remission group were higher than those in the remission group(P＜0.05).pathological staging Ⅲ～Ⅳ,elevated 24 h urine protein level,and elevated urinary CXCL10 and CXCL16 levels were independent risk factors for non-remission treatment in patients with IMN(P＜0.05).The areas under the curve(AUC)of urinary CXCL10 and CXCL16 levels for predicting non-remission treatment in patients with IMN alone and in combination were 0.783,0.785,and 0.875,respectively,the combined detection had the highest predictive efficacy(P＜0.05).Conclusion:Urinary CXCL10 and CXCL16 levels are elevated in patients with IMN,it is closely related to the pathological staging of patients and the therapeutic efficacy,the combined detection of urinary CXCL10 and CXCL16 has a high value in predicting the therapeutic efficacy in patients with IMN.

Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To investigate the expression and clinical significance of urinary C-X-C motif chemokine ligand 10(CXCL10)and C-X-C motif chemokine ligand 16(CXCL16)in patients with idiopathic membranous nephropathy(IMN).Methods:A total of 131 patients with IMN(IMN group)who were treated in Zhejiang Provincial Corps Hospital of the Chinese People's Armed Police Force from December 2020 to June 2022 were prospectively selected,131 healthy volunteers(control group)who underwent physical examination during the same period were selected.Patients with IMN were divided into stage Ⅰ group(25 cases),stage Ⅱ group(68 cases),stage Ⅲ group(22 cases)and stage Ⅳ group(16 cases)according to pathological staging,patients were divided into non-remission group(33 cases)and remission group(98 cases)based on the therapeutic efficacy after a 2-year follow-up.Urinary CXCL10 and CXCL16 levels were measured by enzyme-linked immunosorbent assay.Clinical data of patients with IMN were collected,The relationship between urinary CXCL10,CXCL16 levels and pathological staging in patients with IMN was analysied by Spearman/pearson correlation.Multivariate logistic regression analysis influencing factors on non-remission treatment in patients with IMN,and receiver operating characteristic(ROC)curves were used to assess the predictive value Of urinary CXCL10,CXCL16 levels for non-remission treatment in patients with IMN.Results:Urinary CXCL10 and CXCL16 levels in the IMN group were significantly higher than those in the control group(P＜0.05).Urinary CXCL10 and CXCL16 levels were the highest in stage Ⅳ group,urinary CXCL10 and CXCL16 levels in stage Ⅲ group were higher than those in stage Ⅱ group and stage Ⅰ group,and urinary CXCL10 and CXCL16 levels in stage Ⅱ group were higher than those in stage Ⅰ group(P＜0.05).Urinary CXCL10 and CXCL16 levels in patients with IMN were positively correlated with pathological staging,urinary CXCL10 were positively correlated with CXCL16(P＜0.05).Urinary CXCL10 and CXCL16 in non-remission group were higher than those in the remission group(P＜0.05).pathological staging Ⅲ～Ⅳ,elevated 24 h urine protein level,and elevated urinary CXCL10 and CXCL16 levels were independent risk factors for non-remission treatment in patients with IMN(P＜0.05).The areas under the curve(AUC)of urinary CXCL10 and CXCL16 levels for predicting non-remission treatment in patients with IMN alone and in combination were 0.783,0.785,and 0.875,respectively,the combined detection had the highest predictive efficacy(P＜0.05).Conclusion:Urinary CXCL10 and CXCL16 levels are elevated in patients with IMN,it is closely related to the pathological staging of patients and the therapeutic efficacy,the combined detection of urinary CXCL10 and CXCL16 has a high value in predicting the therapeutic efficacy in patients with IMN.

Objective To evaluate the surgical technique and clinical value of laparoscopic bladder diverticulectomy guided by inserting ureteral catheters into the diverticulum under plasmakinetic resectoscope.Methods From December 2018 to May 2024,9 patients underwent laparoscopic bladder diverticulectomy in combination with resectoscope.Each patient had a solitary bladder diverticulum with a median maximum diameter of 6.40(5.70,7.40)cm(range:5.0～8.5 cm).Among the 9 patients,3 patients had concurrent benign prostatic hyperplasia(BPH)and simultaneously underwent transurethral plasmakinetic resection of the prostate;1 patient had concurrent both BPH and bladder calculi,requiring simultaneously underwent plasmakinetic resection of the prostate and bladder calculi removal;2 patients required ureteral reimplantation as the diverticulum was directly involving the ureteral orifice;1 case underwent ureteroscopic double-J stent implantation because the opening of the ipsilateral ureter was adjacent to the entrance of the diverticulum.Results Bladder diverticulectomy was successfully performed in the all patients.Median operative time was 160.00(120.00,317.50)min(range:85～345 min).Median estimated blood loss was 20.00(10.00,150.00)mL(range:10～300 mL).No iatrogenic injuries to adjacent organs were observed.Pelvic drains were removed 1～3 d postoperatively,with no urine leakage.Urinary catheters were maintained for 7～10 d after operation.Follow-up at 3～12 months showed no recurrence or hydronephrosis in any of the patients.Conclusion Laparoscopic resection of bladder diverticula guided by ureteral catheter placed into bladder diverticula by means of resectoscope has the advantages of less trauma,less bleeding and faster recovery,and is an effective measure for the treatment of bladder diverticula.

Objective To analyze the clinical manifestations and genetic etiology of three families with hereditary spastic paraplegia(HSP).Methods Gene analysis was performed on patients of the three HSP families from the Gansu Provincial Maternity and Child-care Hospital.Results The proband of family 1 was autosomal recessive spastic paraplegia type 35 caused by homozygous variant c.159_176delGGCGGGCCAGGACATCAG(p.Arg53_Ser59delinsSer)in FA2H.The proband in family 2 was autosomal recessive spastic paraplegia type 47 caused by homozygous variant c.1399G>T(p.Glu467Ter)in AP4B1,and the proband in family 3 was autosomal recessive spastic paraplegia type 11 caused by homozygous variation c.7023C>G(p.Tyr2341Ter)in SPG11.Among them,the variant c.1399G>T(p.Glu467Ter)of AP4B1 is a novel variant,that has not been reported before,according to the ACMG guidelines,the pathogenicity of this variant is pathogenic.Conclusion This study has expanded the variant spectrum of AP4B1 which provides basic data to improve clinical understanding and diagnostic capabilities of HSP patients.