Objective The prevalence of drug-resistant Mycobacterium tuberculosis (Mtb) strains is exacerbating the global burden of tuberculosis (TB), highlighting the urgent need for new treatment strategies for TB. Methods The recombinant adenovirus vaccine expressing cyclic di-adenosine monophosphate (c-di-AMP) phosphodiesterase B (CnpB) (rAd-CnpB), was administered to normal mice via mucosal immunization, either alone or in combination with drug therapy, to treat Mtb respiratory infections in mice.Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of antibodies in serum and bronchoalveolar lavage fluid (BALF). Real-time quantitative PCR was performed to assess the transcription levels of cytokines interferon γ(IFN-γ) and interleukin 10(IL-10) in mouse lungs. Flow cytometry was used to determine the proportions of CD4⁺ and CD8⁺ T cell subsets in the lungs and spleens. ELISA was employed to measure the levels of cytokines IFN-γ, IL-2, IL-10, inflammatory factors IL-6, and tumor necrosis factor α (TNF-α) secreted by spleen cells following antigen stimulation. The bacteria loads in the lungs and spleens of Mtb-infected mice were enumerated by plate counting methods. Resluts Intranasal immunization with rAd-CnpB induced high titers of IgG in mouse serum and the production of IgG and IgA in BALF, along with alterations in T lymphocyte subsets in the lungs and spleens. Administration of rAd-CnpB, either alone or in combination with drugs, to Mtb-infected mice significantly increased serum IgG levels as well as IgA and IgG levels in BALF. rAd-CnpB immunization promoted the secretion of CnpB-specific cytokines and inflammatory factors by splenocytes in Mtb-infected mice. However, rAd-CnpB immunotherapy, either alone or combined with drugs, did not significantly affect the bacterial loads in the lungs and spleens of mice with Mtb respiratory infections. Conclusion Mucosal immunization with rAd-CnpB induced significant mucosal, humoral and cellular immune responses in mice, and significantly enhanced CnpB-specific cellular immune responses in Mtb-infected mice.
Animals ; Adenoviridae/immunology* ; Mycobacterium tuberculosis/genetics* ; Mice ; Female ; Phosphoric Diester Hydrolases/genetics* ; Tuberculosis Vaccines/administration & dosage* ; Tuberculosis/prevention & control* ; Mice, Inbred BALB C ; Cytokines ; Lung/microbiology* ; Immunization ; Bronchoalveolar Lavage Fluid/immunology* ; Immunity, Mucosal

Objective To analyze the clinical characteristics and the antimicrobial resistance of respiratory tract infection in children in Baoshan City,guide clinicians to rationally apply antibiotics,and improve the success rate of treatment.Methods Retrospective analysis of the distribution characteristics and drug sensitivity results of 1039 strains of pathogens detected in pediatric inpatients of hospitals from 2019 to 2022 was conducted.Results The main pathogens causing the respiratory infections in children in Baoshan area were Streptococcus pneumoniae,Escherichia coli,Staphylococcus aureus,Haemophilus influenzae,Klebsiella pneumoniae and Pseudomonas aeruginosa.Analysis of the drug sensitivity results of pathogenic bacteria with a detected quantity greater than 80 revealed that Streptococcus pneumoniae had a high resistance rate to erythromycin,clindamycin,and compound sulfamethoxazole.The resistance rates of penicillin,ceftriaxone,cefotaxime,and meropenem were P<0.05,and the difference was statistically significan.Methicillin-resistant Staphylococcus aureus(MRSA)was11.1%;CTX/CRO-R-ECO,CTX/CRO-R-KPN,CR-ECO and CR-KPN were lower than the 2021 ISPED level;The P.aeruginosa drug resistance rate and H.influenzae's ampicillin and ampicillin/sulbactam were higher than the 2021 ISPED level.Conclusion The treatment of respiratory tract infections in pediatric patients faces great challenges.The non-standard use of empirical medication has led to the emergence of multidrug-resistant bacteria,and the selection of anti infection treatment drugs is limited.Therefore,it is imperative to grasp the epidemic characteristics and drug resistance of pathogenic bacteria in the local area.

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.
Animals ; Mice ; Mycobacterium tuberculosis ; Antigens, Bacterial ; Immunization ; Nanoparticles ; Vaccines, Subunit ; Mice, Inbred BALB C

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.

Objective:To explore the relationship between age at menarche and general obesity (based on BMI) and central obesity (based on WC or WHtR) in middle-aged and elderly women in China.Methods:A total of 6 363 women from the China Health and Retirement Longitudinal Study were included. Restricted cubic splines based on binary logistic regressions were used to analyze the relationship between age at menarche and the risk of obesity. Age at menarche was divided into four groups: ≤13, 14- (control group), 16- , and ≥18 years old. Binary logistic regressions were applied to analyze the relationship between the continuous or grouped variable of age at menarche and the risk of obesity.Results:After adjusting potential confounders, the age at menarche showed a negative linear relationship with the risk of general obesity and central obesity. The risk for obesity based on BMI, WC and WHtR significantly decreased by 6% ( OR=0.94, 95% CI: 0.90-0.99), 4% ( OR=0.96, 95% CI: 0.92-1.00), and 6% ( OR=0.94, 95% CI: 0.90-0.99) for each 1 year increase in age at menarche. Compared with participants who had menarche at age 14- years old, the risk for obesity based on BMI ( OR=0.71, 95% CI: 0.55-0.91), WC ( OR=0.75, 95% CI: 0.62-0.92) and WHtR ( OR=0.76, 95% CI: 0.61-0.96) significantly decreased by 29%, 25%, and 24% in participants who had menarche at age ≥18 years old. Conclusions:There was a negative linear relationship between age at menarche and the risk for general obesity and central obesity in middle-aged and elderly women in China. Older age at menarche might be negatively associated with risk for obesity in middle-aged and elderly women.

Objective:To explore the influencing factors of postoperative coping style of patients with esophageal cancer.Methods:This study was a cross-sectional study. From July 2018 to July 2020, convenience sampling was used to select 65 patients with esophageal cancer who underwent radical surgery for esophageal cancer in a ClassⅢ Grade A hospital in Henan Province as the research object. The General Information Questionnaire and the Chinese version of the Medical Coping Modes Questionnaire (MCMQ) were used to investigate the patients one day before the patients were discharged. Single factor analysis was used to analyze influencing factors. A total of 65 questionnaires were distributed and 65 valid questionnaires were returned with the valid response rate of 100%.Results:The results of single factor analysis showed that there were statistically significant differences in the confrontation dimension scores of patients with different ages, education levels, and family monthly income per capita ( P<0.05) . There were statistically significant differences in the avoidance dimension scores of patients with different genders and ages ( P<0.05) . There were statistically significant differences in the resignation dimension scores of patients with different ages, occupational status, and family monthly income per capita ( P<0.05) . Conclusions:Age, gender, occupational status, education level, and family monthly income per capita are the influencing factors of postoperative coping style of patients with esophageal cancer. Medical and nursing staff can take targeted intervention measures based on their influencing factors and guide patients to adopt a positive coping style to face the disease.

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders.In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment.After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders.In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment.After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Objective To investigate the clinical value of ultrasound examination of carpal canal structure in patients with mild hand-arm vibration disease.Methods A total of 29 patients (58 wrists) with mild hand-arm vibration disease who were treated in Shenzhen Prevention and Treatment Center for Occupational Diseases from May to December,2015 were enrolled as observation group,and 20 healthy volunteers (40 wrists) were enrolled as the control group.Color Doppler ultrasound was used to observe the morphology and echo of the median nerve in the carpal canal and 9 muscle tendons and transverse carpal ligament.The thickness of transverse carpal ligament and diameter of the median nerve at the level of the hamulus of hamate bone were measured,as well as the cross-sectional area of the median nerve at the level of pisiform bone.Results In the 29 patients with hand-arm vibration disease patients in the observation group,8 experienced entrapment of the median nerve in the carpal canal,among whom 5 had entrapment in both wrists;there were 13 wrists (23％) with nerve entrapment and 45 wrists (77％) without nerve entrapment.Compared with the control group,the patients with hand-arm vibration disease and nerve entrapment in the observation group showed significant thickening of the transverse carpal ligament at the level of the hamulus of hamate bone and a significant increase in the crosssectional area of the median nerve at the level of pisiform bone (P＜0.05),while there were no significant differences in the thickness of transverse carpal ligament at the level of the hamulus of hamate bone and the crosssectional area of the median nerve at the level of pisiform bone (t=-9.397 and-4.385,both P＞0.05).Conclusion Ultrasound examination can clearly show the radiological changes of carpal canal contents in patients with mild hand-arm vibration disease and has a certain diagnostic value in nerve damage in patients with hand-arm vibration disease.

Objective To investigate the clinical value of ultrasound examination of carpal canal structure in patients with mild hand-arm vibration disease.Methods A total of 29 patients (58 wrists) with mild hand-arm vibration disease who were treated in Shenzhen Prevention and Treatment Center for Occupational Diseases from May to December,2015 were enrolled as observation group,and 20 healthy volunteers (40 wrists) were enrolled as the control group.Color Doppler ultrasound was used to observe the morphology and echo of the median nerve in the carpal canal and 9 muscle tendons and transverse carpal ligament.The thickness of transverse carpal ligament and diameter of the median nerve at the level of the hamulus of hamate bone were measured,as well as the cross-sectional area of the median nerve at the level of pisiform bone.Results In the 29 patients with hand-arm vibration disease patients in the observation group,8 experienced entrapment of the median nerve in the carpal canal,among whom 5 had entrapment in both wrists;there were 13 wrists (23％) with nerve entrapment and 45 wrists (77％) without nerve entrapment.Compared with the control group,the patients with hand-arm vibration disease and nerve entrapment in the observation group showed significant thickening of the transverse carpal ligament at the level of the hamulus of hamate bone and a significant increase in the crosssectional area of the median nerve at the level of pisiform bone (P＜0.05),while there were no significant differences in the thickness of transverse carpal ligament at the level of the hamulus of hamate bone and the crosssectional area of the median nerve at the level of pisiform bone (t=-9.397 and-4.385,both P＞0.05).Conclusion Ultrasound examination can clearly show the radiological changes of carpal canal contents in patients with mild hand-arm vibration disease and has a certain diagnostic value in nerve damage in patients with hand-arm vibration disease.