Objective To investigate the role and possible mechanism of celastrol(Cel)in sodium oxalate(NaOx)-induced acute kidney injury(AKI)and crystal deposition in the kidney tissues in mice.Methods Male C57BL/6 mice(aged 8～12 weeks,weighing 22～24 g)were randomly divided into 3 groups.Saline group(control group,intraperitoneal injection with normal saline and drinking water freely),NaOx group(injured group,intraperitoneal injection of 75 mg/kg NaOx,and drinking water containing 50 μmol/L NaOx),and NaOx+Cel group(treatment group,intraperitoneal injection of 1 mg/kg Cel firstly and then 75 mg/kg NaOx in 24 h later,drinking water containing 50 μmol/L NaOx).All specimens were collected in 24 h after NaOx injection.HK-2 cells were randomly divided into 4 groups:Medium group(no treatment),NaOx group(500 μmol/L NaOx),NaOx+Cel group(400 nmol/L Cel pre-treatment for 2 h followed by 500 μmol/L NaOx treatment),and NaOx+Cel+BA group[8 μmol/L betulinic acid(BA,NF-κB agonist)after the interventions as the NaOx+Cel group].Cells of each group were collected in 24 h after corresponding treatments.Von Koosa and cell adhesion assays were used to observe crystal deposition.HE staining was employed to observe renal histopathology and score the damage.CCK-8 assay was utilized to detect cell viability to obtain the optimal concentrations of NaOx and Cel.Serum urea and creatinine levels were detected.Immunohisotochemical assay was conducted to detect the expression of OPN,CD44,KIM-1,NGAL,p65,IL-1β,BAX,and Caspase-3,and Western blotting was performed for protein levels of OPN,CD44,KIM-1,p65,P-p65 and IL-1β.Results The mice in the NaOx+Cel group showed reduced crystal deposition(P<0.0001),attenuated renal tubular damage(P<0.01),decreased serum urea and creatinine levels(P<0.05),and declined expression levels of the renal adhesion molecules OPN and CD44,the kidney injury molecules KIM-1 and NGAL,the inflammation-associated molecules p65 and IL-1β,and the apoptosis related molecules BAX and Caspase-3 when compared with the NaOx group(P<0.05).In in vitro study,the NaOx+Cel group showed reduced crystal adhesion(P<0.0001),decreased expression of the adhesion molecules OPN and CD44(P<0.05),down-regulation of the inflammatory molecule IL-1β and P-p65/p65 ratio(P<0.05),and down-regulation of the renal injury molecule KIM-1(P<0.05)when compared with the NaOx group.In the NaOx+Cel+BA group,crystal adhesion was significantly increased(P<0.0001),the inflammatory molecule IL-1β and the ratio of P-p65/p65 were increased(P<0.05),and the kidney injury molecule KIM-1 was increased when compared with the NaOx+Cel group(P<0.05).Conclusion Cel may reduce NaOx-induced crystal deposition and AKI by inhibiting NF-κB activation.

To screen new antigens for novel tuberculosis(TB)vaccine research,we used bioinformatics to predict the B and T cell epitopes of Rv2318,and evaluated the immunogenicity of Rv2318 and its T/B epitope peptides(Rv2318p).The recombinant plas-mids pET32a-Rv2318 and pET32a-Rv2318p were constructed through gene synthesis methods.The recombinant proteins were ex-pressed in a prokaryotic system and purified with nickel affinity chromatography.Proteins were identified with SDS-PAGE and western blotting.BALB/c mice were immunized subcutaneously with the recombinant proteins to evaluate immunogenicity.Sera were collected,and antigen specific antibody titers were evaluated with ELISA.Splenocytes were isolated,and cytokines and T cell proliferation were analyzed with ELISA and flow cytometry,respectively.Rv2318 included two epitope fragments,aa10-130 and 350-410.SDS-PAGE and western blotting indicated that the target proteins were expressed and purified correctly,and their relative molecular weights were-approximately 68 kD and 42 kD,respectively.Rv2318 and Rv2318p induced stronger humoral immune responses than observed in the control groups(P<0.000 1,n=6).Compared with Rv2318,Rv2318p showed significantly greater enhancement of specific IgG and IgG subclass antibodies(P<0.000 1,n=6).In addition,Rv2318p increased the ratio of IgG2a/IgG1,thus indicating that it primarily induced a cellular immune response biased toward the Th1 type.Cytokine experiments revealed that IFN-γ,IL-2,IL-6,and IL-4 significantly increased after immunization with Rv2318p(P all<0.01,n=6),particularly Th1 type cytokines(IFN-γ and IL-2).Furthermore,Rv2318 increased the expression of only IL-2 and IL-6,particularly IL-6(P all<0.01,n=6).Although Rv2318 in-duced more IFN-γ,we observed no significant difference between Rv2318 and PBS immunized mice.Importantly,Rv2318p stimu-lated mice to express IFN-γ at 842 pg/mL,approximately 3 times the level elicited by Rv2318.Whereas both proteins increased the proportions of CD4+and CD8+T cells,Rv2318p promoted greater proliferation of T lymphocytes.These data indicated that both Rv2318 and its epitope peptides enhanced humoral and cellular immune responses,whereas the epitope peptides notably triggered a stronger Th1 type cellular response.In conclusion,the recombinant protein Rv2318 and its epitope peptides showed favorable immunogenicity,and the immunogenicity of Rv2318p was superior to that of Rv2318.This study provides a theoretical basis for TB vaccine development.

This study was aimed at analyzing the epidemiological and drug resistance characteristics of tuberculosis at a desig-nated tuberculosis hospital in Hunan Province in 2024.Patients diagnosed with TB at the hospital between April and October 2024 were included in the study.Demographic data,clinical information,and drug sensitivity test results were collected from the hospital′s electronic medical record system.Descriptive statistics,the chi-square test,and logistic regression were used to analyze the epidemic characteristics,drug resistance characteristics,and factors influencing tuberculosis.Whole genome sequencing of isolates was per-formed,and lineage classification and drug resistance gene mutations were detected with TB-Profiler.The male-to-female ratio was 2.72∶1,and the median age was 56(IQR:43-66)years.Among the 391 patients,most were farmers(46.8%,183/391)and were pri-marily from Changsha(41.1%,162/391).Significant differences were observed in sex and occupation between pulmonary tuberculosis(PTB)and extrapulmonary tuberculosis(EPTB).The overall prevalence of any type of drug resistance of tuberculosis was 33.25%,and the multidrug resistance TB(MDR-TB)and poly-drug resistance(PR-TB)rates were 14.23%and 4.35%,respectively.The re-sistance rates to rifampicin(RIF),isoniazid(INH),ethambutol(EMB),and streptomycin(SM)were 17.90%,22.25%,6.39%,and 20.20%,respectively.Multivariable logistic regression analysis indicated that both diabetes(OR:2.295,95%CI:1.082-4.866)and retreatment(OR:17.822,95%CI:8.343-38.072)were risk factors for developing MDR-TB.Lineage 2(L2)strains accounted for 64.40%(136/191),whereas lineage 4(L4)accounted for 28.80%(55/191).The most common drug resistance mutations were katG Ser315Thr(62.50%,20/32)for INH,rpoB Ser450Leu(50.00%,12/24)for RIF,embB Met306Val(55.56%,5/9)for EMB,and rpsL Lys43Arg(80.95%,34/42)for SM.In conclusion,TB drug resistance was found to be a serious problem at a designated tu-berculosis hospital in Hunan in 2024.Strengthening the treatment and management of patients infected with L2 strains,those with co-morbid diabetes,and retreatment cases is crucial for preventing and controlling the emergence of drug-resistant TB.

To screen new antigens for novel tuberculosis(TB)vaccine research,we used bioinformatics to predict the B and T cell epitopes of Rv2318,and evaluated the immunogenicity of Rv2318 and its T/B epitope peptides(Rv2318p).The recombinant plas-mids pET32a-Rv2318 and pET32a-Rv2318p were constructed through gene synthesis methods.The recombinant proteins were ex-pressed in a prokaryotic system and purified with nickel affinity chromatography.Proteins were identified with SDS-PAGE and western blotting.BALB/c mice were immunized subcutaneously with the recombinant proteins to evaluate immunogenicity.Sera were collected,and antigen specific antibody titers were evaluated with ELISA.Splenocytes were isolated,and cytokines and T cell proliferation were analyzed with ELISA and flow cytometry,respectively.Rv2318 included two epitope fragments,aa10-130 and 350-410.SDS-PAGE and western blotting indicated that the target proteins were expressed and purified correctly,and their relative molecular weights were-approximately 68 kD and 42 kD,respectively.Rv2318 and Rv2318p induced stronger humoral immune responses than observed in the control groups(P<0.000 1,n=6).Compared with Rv2318,Rv2318p showed significantly greater enhancement of specific IgG and IgG subclass antibodies(P<0.000 1,n=6).In addition,Rv2318p increased the ratio of IgG2a/IgG1,thus indicating that it primarily induced a cellular immune response biased toward the Th1 type.Cytokine experiments revealed that IFN-γ,IL-2,IL-6,and IL-4 significantly increased after immunization with Rv2318p(P all<0.01,n=6),particularly Th1 type cytokines(IFN-γ and IL-2).Furthermore,Rv2318 increased the expression of only IL-2 and IL-6,particularly IL-6(P all<0.01,n=6).Although Rv2318 in-duced more IFN-γ,we observed no significant difference between Rv2318 and PBS immunized mice.Importantly,Rv2318p stimu-lated mice to express IFN-γ at 842 pg/mL,approximately 3 times the level elicited by Rv2318.Whereas both proteins increased the proportions of CD4+and CD8+T cells,Rv2318p promoted greater proliferation of T lymphocytes.These data indicated that both Rv2318 and its epitope peptides enhanced humoral and cellular immune responses,whereas the epitope peptides notably triggered a stronger Th1 type cellular response.In conclusion,the recombinant protein Rv2318 and its epitope peptides showed favorable immunogenicity,and the immunogenicity of Rv2318p was superior to that of Rv2318.This study provides a theoretical basis for TB vaccine development.

This study was aimed at analyzing the epidemiological and drug resistance characteristics of tuberculosis at a desig-nated tuberculosis hospital in Hunan Province in 2024.Patients diagnosed with TB at the hospital between April and October 2024 were included in the study.Demographic data,clinical information,and drug sensitivity test results were collected from the hospital′s electronic medical record system.Descriptive statistics,the chi-square test,and logistic regression were used to analyze the epidemic characteristics,drug resistance characteristics,and factors influencing tuberculosis.Whole genome sequencing of isolates was per-formed,and lineage classification and drug resistance gene mutations were detected with TB-Profiler.The male-to-female ratio was 2.72∶1,and the median age was 56(IQR:43-66)years.Among the 391 patients,most were farmers(46.8%,183/391)and were pri-marily from Changsha(41.1%,162/391).Significant differences were observed in sex and occupation between pulmonary tuberculosis(PTB)and extrapulmonary tuberculosis(EPTB).The overall prevalence of any type of drug resistance of tuberculosis was 33.25%,and the multidrug resistance TB(MDR-TB)and poly-drug resistance(PR-TB)rates were 14.23%and 4.35%,respectively.The re-sistance rates to rifampicin(RIF),isoniazid(INH),ethambutol(EMB),and streptomycin(SM)were 17.90%,22.25%,6.39%,and 20.20%,respectively.Multivariable logistic regression analysis indicated that both diabetes(OR:2.295,95%CI:1.082-4.866)and retreatment(OR:17.822,95%CI:8.343-38.072)were risk factors for developing MDR-TB.Lineage 2(L2)strains accounted for 64.40%(136/191),whereas lineage 4(L4)accounted for 28.80%(55/191).The most common drug resistance mutations were katG Ser315Thr(62.50%,20/32)for INH,rpoB Ser450Leu(50.00%,12/24)for RIF,embB Met306Val(55.56%,5/9)for EMB,and rpsL Lys43Arg(80.95%,34/42)for SM.In conclusion,TB drug resistance was found to be a serious problem at a designated tu-berculosis hospital in Hunan in 2024.Strengthening the treatment and management of patients infected with L2 strains,those with co-morbid diabetes,and retreatment cases is crucial for preventing and controlling the emergence of drug-resistant TB.

To investigate the clinical value of endoscopic ultrasound-guided puncture drainage in the treatment for liver abscess and abdominal and pelvic abscess with difficulty in conventional puncture drainage. Data of 12 such patients in the Second Affiliated Hospital of Soochow University from January 2015 to November 2023 were retrospectivly analyzed. Results showed liver abscess in 4 cases, abdominal and pelvic abscess in 8 cases. All patients had fever with varying degrees of abdominal pain. Twelve patients with liver abscess and abdominal and pelvic abscess received 13 times of endoscopic ultrasound-guided puncture (1 patient with a large abdominal and pelvic cyst complicated with infection received transgastric and transrectal puncture of 2 times). The puncture needle was successfully penetrated into the pus cavity. Four patients with liver abscess underwent endoscopic ultrasound-guided suction and irrigation, and the abscess was almost completely aspirated. Seven patients with abdominal and pelvic abscess underwent endoscopic ultrasound-guided suction and irrigation, of which 5 cases were almost completely aspirated, and 2 cases had poor drainage effect due to the viscous pus (1 case returned to normal temperature after anti-infection treatment; 1 case had recurrent fever after the operation, and septic shock and death occurred 2 weeks after the operation). A patient with recurrent abdominal and pelvic sclerosis after the operation had multiple abscesses in the abdomen and pelvis, and percutaneous CT-guided drainage was performed for abdominal abscess, but the fever was still repeated. Endoscopic ultrasound-guided balloon dilation plus double pig tail and nasobiliary duct drainage were performed. The patient's temperature returned to normal and abdominal pain was relieved 48 hours after the operation. The total effective rate of abscess drainage was 83.3% (10/12), and the effective rate of suction combined with irrigation for abscess drainage was 81.8% (9/11), and no operation-related complications were observed in all patients. After 3 months of follow-up, no recurrence occurred in 10 patients with effective drainage of abscess, and abscess was self-absorbed in 1 patient with pelvic abscess without effective drainage and no recurrence was observed. Endoscopic ultrasound-guided puncture drainage is of certain clinical value for some liver abscesses and abdominal and pelvic abscesses that are difficult to be drained by conventional puncture, and can reduce the secondary trauma caused by surgical operations.

To investigate the clinical value of endoscopic ultrasound-guided puncture drainage in the treatment for liver abscess and abdominal and pelvic abscess with difficulty in conventional puncture drainage. Data of 12 such patients in the Second Affiliated Hospital of Soochow University from January 2015 to November 2023 were retrospectivly analyzed. Results showed liver abscess in 4 cases, abdominal and pelvic abscess in 8 cases. All patients had fever with varying degrees of abdominal pain. Twelve patients with liver abscess and abdominal and pelvic abscess received 13 times of endoscopic ultrasound-guided puncture (1 patient with a large abdominal and pelvic cyst complicated with infection received transgastric and transrectal puncture of 2 times). The puncture needle was successfully penetrated into the pus cavity. Four patients with liver abscess underwent endoscopic ultrasound-guided suction and irrigation, and the abscess was almost completely aspirated. Seven patients with abdominal and pelvic abscess underwent endoscopic ultrasound-guided suction and irrigation, of which 5 cases were almost completely aspirated, and 2 cases had poor drainage effect due to the viscous pus (1 case returned to normal temperature after anti-infection treatment; 1 case had recurrent fever after the operation, and septic shock and death occurred 2 weeks after the operation). A patient with recurrent abdominal and pelvic sclerosis after the operation had multiple abscesses in the abdomen and pelvis, and percutaneous CT-guided drainage was performed for abdominal abscess, but the fever was still repeated. Endoscopic ultrasound-guided balloon dilation plus double pig tail and nasobiliary duct drainage were performed. The patient's temperature returned to normal and abdominal pain was relieved 48 hours after the operation. The total effective rate of abscess drainage was 83.3% (10/12), and the effective rate of suction combined with irrigation for abscess drainage was 81.8% (9/11), and no operation-related complications were observed in all patients. After 3 months of follow-up, no recurrence occurred in 10 patients with effective drainage of abscess, and abscess was self-absorbed in 1 patient with pelvic abscess without effective drainage and no recurrence was observed. Endoscopic ultrasound-guided puncture drainage is of certain clinical value for some liver abscesses and abdominal and pelvic abscesses that are difficult to be drained by conventional puncture, and can reduce the secondary trauma caused by surgical operations.

A 11-year old female patient with severe thalassemia, receipt a lentivirus-based cell and gene therapy (CGT) therapy in Shenzhen Children′s Hosptial on July 27th, 2021. At the two follow-up visits after discharge, patient were continuously tested positive for HIV screening through HIV Ag/Ab Combo assay (chemiluminescence Immunoassay), and the viral load results of HIV-1 nucleic acid testing (NAT) were both>5 000 copies/ml. The patient can be diagnosed with HIV infection according to the National Guideline for Detection of HIV/AIDS(2020 Revised Edition). The thorough investigation findings and supplementary experiment results indicated that the false-positive HIV-1 NAT results was caused by cross-reactivity between the target sites detected by conventional HIV-1 NAT reagents and the lentiviral vectors fragments integrated into the genome of patient′s hematopoietic stem/progenitor cells. In conclusion, it is important for laboratories to select appropriate HIV-1 NAT testing platforms which won′t cause cross-reactivity for the testing of samples from patients who have been treated with HIV-derived vectors. It is also recommended to design and develop NAT testing platforms with multiple target regions labeled by different fluorescents for HIV NAT supplementation experiment to reduce the risk of false-positive diagnoses of HIV infection.

Objective To explore the clinical value of endoscopic intervention in preventing rebleeding of Forrest Ⅱb grade ulcers.Method A retrospective analysis was conducted on the clinical data of 114 patients from January 2015 to April 2023 due to gastrointestinal bleeding,who were confirmed by gastroscopy as Forrest Ⅱb grade ulcers.86 (75.4％,86/114) patients received endoscopic treatment as endoscopic treatment group,while 28 patients only received medication treatment as medication treatment group.Compare the effectiveness of endoscopic treatment and different endoscopic hemostatic methods for preventing rebleeding.Results There were no statistically significant differences in age,gender,clinical symptom,systolic pressure,hemoglobin concentration,and ulcer site between endoscopic and medication treatment patients (P>0.05).In terms of ulcer size,the length of ulcer in the endoscopic treatment group was smaller than that in the medication treatment group[(9.5±5.3) mm vs (12.8±7.7) mm],the difference was statistically significant (P=0.013).The rebleeding rate of medication treatment group was 21.4％ (6/28);Among the endoscopic treatment group,85 patients (98.8％,85/86) successfully underwent endoscopic treatment,with a rebleeding rate of 11.8％ (10/85),which was lower than that of medication treatment group,but the difference was not statistically significant (P=0.337).Among the patients who successfully underwent endoscopic treatment,62 cases were treated with injection of diluted adrenaline alone,6 cases with titanium clips,and 17 cases were treated with electrocoagulation or electrocoagulation combined with other hemostatic methods.The rebleeding rate were 12.9％ (8/62),16.7％ (1/6),and 5.9％ (1/17),respectively,which were lower than that of medication treatment patients,but the difference was not statistically significant (P=0.474).Due to the need for endoscopic treatment,15 patients were treated with a snare or thermal hemostatic forceps to remove the surface blood clot of the ulcer.Among them,3 cases had jet bleeding at the base (2 cases were successfully stopped by electrocoagulation;1 case had a large amount of bleeding,but endoscopic hemostasis failed,and intervention embolization successfully stopped the bleeding).Among of 16 patients with rebleeding,3 patients were treated with conservative management,and all of them were successfully stopped bleeding;6 cases underwent endoscopic treatment again,of which 4 cases were successfully hemostasis by endoscopy,and 2 cases were successfully hemostasis by surgery after endoscopic hemostasis failure;interventional embolization in 1 case,and successfully hemostasis;6 patients underwent direct surgical procedures,all of which successfully stopped bleeding,but one patient developed multiple organ failure during hospitalization and died without bleeding.Conclusion Endoscopic intervention can to some extent reduce the incidence of rebleeding in Forrest Ⅱb grade ulcers.The effect of electrocoagulation hemostasis on preventing rebleeding is better than that of injection dilution adrenaline method.However,there is a risk of iatrogenic rebleeding when removing blood clots on the surface of ulcers,and careful selection should be made when conditions permit.

Objective To explore the clinical value of endoscopic intervention in preventing rebleeding of Forrest Ⅱb grade ulcers.Method A retrospective analysis was conducted on the clinical data of 114 patients from January 2015 to April 2023 due to gastrointestinal bleeding,who were confirmed by gastroscopy as Forrest Ⅱb grade ulcers.86 (75.4％,86/114) patients received endoscopic treatment as endoscopic treatment group,while 28 patients only received medication treatment as medication treatment group.Compare the effectiveness of endoscopic treatment and different endoscopic hemostatic methods for preventing rebleeding.Results There were no statistically significant differences in age,gender,clinical symptom,systolic pressure,hemoglobin concentration,and ulcer site between endoscopic and medication treatment patients (P>0.05).In terms of ulcer size,the length of ulcer in the endoscopic treatment group was smaller than that in the medication treatment group[(9.5±5.3) mm vs (12.8±7.7) mm],the difference was statistically significant (P=0.013).The rebleeding rate of medication treatment group was 21.4％ (6/28);Among the endoscopic treatment group,85 patients (98.8％,85/86) successfully underwent endoscopic treatment,with a rebleeding rate of 11.8％ (10/85),which was lower than that of medication treatment group,but the difference was not statistically significant (P=0.337).Among the patients who successfully underwent endoscopic treatment,62 cases were treated with injection of diluted adrenaline alone,6 cases with titanium clips,and 17 cases were treated with electrocoagulation or electrocoagulation combined with other hemostatic methods.The rebleeding rate were 12.9％ (8/62),16.7％ (1/6),and 5.9％ (1/17),respectively,which were lower than that of medication treatment patients,but the difference was not statistically significant (P=0.474).Due to the need for endoscopic treatment,15 patients were treated with a snare or thermal hemostatic forceps to remove the surface blood clot of the ulcer.Among them,3 cases had jet bleeding at the base (2 cases were successfully stopped by electrocoagulation;1 case had a large amount of bleeding,but endoscopic hemostasis failed,and intervention embolization successfully stopped the bleeding).Among of 16 patients with rebleeding,3 patients were treated with conservative management,and all of them were successfully stopped bleeding;6 cases underwent endoscopic treatment again,of which 4 cases were successfully hemostasis by endoscopy,and 2 cases were successfully hemostasis by surgery after endoscopic hemostasis failure;interventional embolization in 1 case,and successfully hemostasis;6 patients underwent direct surgical procedures,all of which successfully stopped bleeding,but one patient developed multiple organ failure during hospitalization and died without bleeding.Conclusion Endoscopic intervention can to some extent reduce the incidence of rebleeding in Forrest Ⅱb grade ulcers.The effect of electrocoagulation hemostasis on preventing rebleeding is better than that of injection dilution adrenaline method.However,there is a risk of iatrogenic rebleeding when removing blood clots on the surface of ulcers,and careful selection should be made when conditions permit.