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

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To construct quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery based on the three-dimensional quality structure model, and provide a basis for evaluating the quality of pelvic floor rehabilitation.Methods:Based on the "structure-process-result" three-dimensional quality structure model, a quality indicator system for pelvic floor rehabilitation management in patients after cervical cancer surgery was constructed by literature review, semi-structured interview and Delphi technique from January to May 2023, and the importance and weight of the indicators was identified.Results:A total of 15 experts were included, including 3 males and 12 females, aged 38-56 (46.79 ± 6.38) years. The effective questionnaire recovery rates of 2 rounds of expert correspondence were 15/15, the authority coefficients of the experts were 0.938 and 0.923, and the Kendall coordination coefficients were 0.139 - 0.337 and 0.107 - 0.152 (all P<0.01). The final quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery included 3 primary indicators, 10 secondary indicators and 42 tertiary indicators. Conclusions:The quality indicator system for pelvic floor rehabilitation in patients after cervical cancer surgery constructed based on three-dimensional quality structure model was scientific and practical, which could be used as an indicator for evaluating the quality of pelvic floor rehabilitation in patients after cervical cancer surgery.

Objective:To design and develop a WeChat mini-program for risk assessment and health management of people at high-risk of stroke.Methods:Relying on the network platforms and smartphones, a WeChat mini-program based health management network platform was designed and developed based on the analysis of the needs of high-risk stroke populations and medical staff for the management of high-risk stroke populations, with health data collection, stroke risk assessment, health education and knowledge base matching and intervention programs and data privacy and security as the key technologies.Results:The mini-program included three ports, such as the patient end, medical staff end and backend management end. It had the main functions of stroke risk assessment, intelligent promotion of health management follow-up plans, recording of health indicators and medication reminders, interactive consultation, and health knowledge promotion.Conclusions:The development of risk assessment and health management WeChat mini-program for high-risk stroke populations and the use of a simple and effective intelligent assessment to realize rapid classification of stroke risk in population lay a foundation for the WeChat mini-program function module to carry out individualized, accurate and efficient brain-heart health management.

Objective:To summarize the best evidence for home self-volume monitoring in patients with chronic heart failure (CHF), so as to provide evidence for accurate monitoring of volume status.Methods:Computer search was conducted for literature on home self-volume monitoring in CHF patients in UpToDate, BMJ best practice, Guidelines International Network, Cochrane Library, PubMed, Embase, CNKI, Wanfang Data, China Biology Medicine disc and other websites and databases. The search period was from establishment of databases to August 31, 2023. After the quality evaluation of various literatures, the evidence was extracted and summarized.Results:A total of 21 literatures were included, and 24 pieces of evidence were summarized from 4 aspects, including monitoring objectives, monitoring content and methods, health education and resource integration and support.Conclusions:This study summarizes the best evidence for home self-monitoring of CHF patients, which is beneficial for nursing staff to provide a basis for providing patients with home self-monitoring plans, thereby improving the accuracy and effectiveness of patient self-monitoring.

Objective To investigate the diagnostic value of detachable string magnetically controlled capsule endoscopy(ds-MCE)in patients with liver cirrhosis.Methods Patients with liver cirrhosis were screened for esophagogastroduodenoscopy(EGD)and ds-MCE examination to assess the accuracy of ds-MCE in identifying gastroesophageal varices,high-risk esophageal varices and portal hypertensive gastropathy using EGD as the gold standard,and evaluate the detection of portal hypertensive enteropathy and the comfort level of patients.Results From May 2021 to July 2022,a total of 53 patients with liver cirrhosis were successfully enrolled.With EGD as the gold standard,ds-MCE detected esophageal varices with 95.45％for sensitivity,100％for specificity and adjusted positive predictive value(PPV),95.65％for adjusted negative predictive value(NPV),and 0.877 for Kappa value(P＜0.001).For detection of gastric varices,ds-MCE had sensitivity,specificity,adjusted PPV,and adjusted NPV of 93.94％,90％,90.38％and 93.69％,and Kappa value of 0.839(P＜0.001).For detection of portal hypertension gastropathy,ds-MCE had sensitivity,specificity,adjusted PPV and adjusted NPV of 80％,90.70％,89.59％and 81.93％,and Kappa value of 0.657(P＜0.001).In differentiating high-risk esophageal varices,the sensitivity,specificity,adjusted PPV,and adjusted NPV were 76％,100％,100％and 77.43％,respectively;Kappa value was 0.770(P＜0.001).Of the patients with liver cirrhosis,26.0％(13/50)were diagnosed with portal hypertensive enteropathy.The main mucosal changes were edema,erythema,and vascular dysplasia.The ds-MCE comfort score of 3(2,4)was higher than that of the traditional EGD 1(0,3)(P＜0.000 1).Conclusion Compared with EGD,ds-MCE is an accurate,safe,feasible and comfortable method for detecting esophagogastric varices and portal hypertensive gastropathy in patients with liver cirrhosis.It is a potential alternative to EGD screening surveillance of gastroesophageal varices in patients with liver cirrhosis.

Objective:To evaluate the effects of different subanesthetic doses of esketamine on lung injury in elderly patients undergoing robot-assisted radical prostatectomy.Methods:Ninety American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ patients, aged 65-80 yr, with body mass index of 19-27 kg/m 2, scheduled for elective robot-assisted radical prostatectomy under general anesthesia, identified as having middle and high risk using the Assess Respiratory Risk in Surgical Patients in Catalonia, were divided into 3 groups ( n=30 each) using a random number table method: low-dose esketamine group (ES1 group), extremely low-dose esketamine group (ES2 group) and control group (C group). In ES1 group, esketamine was intravenously injected as a bolus of 0.2 mg/kg during anesthesia induction followed by an infusion of 0.125 mg·kg -1·h -1 until 30 min before the end of operation. In ES2 group, esketamine was intravenously injected as a bolus of 0.1 mg/kg during anesthesia induction followed by an infusion of 0.015 mg·kg -1·h -1 until 30 min before the end of operation. The equal volume of normal saline was given instead in C group. Radial artery blood samples were collected before anesthesia induction (T 0) and at the end of operation for determination of concentrations of Clara cell secretory protein (CC-16) and soluble form of advanced glycation end products receptor (sRAGE) in serum by enzyme-linked immunosorbent assay. The parameters of respiratory mechanics such as the driving pressure, dynamic lung compliance and mechanical power were recorded at 5 min after mechanical ventilation (T 1), and at 1 and 2 h after Trendelenburg position combined with pneumoperitoneum (T 2-3), and at 5 min before the end of operation (T 4). Blood samples were collected from the radial artery at T 0, T 1, T 3 and in the postanesthesia care unit for blood gas analysis, and the alveolar-arterial partial oxygen pressure difference and oxygenation index were recorded. The adverse reactions within 24 h after operation and the occurrence of postoperative pulmonary complications within 7 days after operation were recorded. Results:Compared with C group, the serum CC-16 and sRAGE concentrations were significantly decreased at the end of operation, the oxygenation index was increased and the alveolar-arterial partial oxygen pressure difference was decreased in the postanesthesia care unit, and the incidence of postoperative nausea reactions within 24 h after operation was decreased in ES1 and ES2 groups ( P<0.05 or 0.01). Compared with ES2 group, the serum CC-16 and sRAGE concentrations were significantly decreased at the end of operation in ES1 group ( P<0.05). There were no statistically significant differences in the driving pressure, dynamic lung compliance and mechanical power at T 1-4 and the incidence of postoperative pulmonary complications within 7 days after surgery among the three groups ( P>0.05). Conclusions:Esketamine given as a subanesthetic bolus of 0.2 mg/kg during anesthesia induction followed by an infusion of 0.125 mg·kg -1·h -1 can alleviate lung injury in elderly patients undergoing robot-assisted radical prostatectomy.

Objective:To observe the effect of combining robot-assisted gait training (RAGT) with task-oriented training (TOT) on the walking ability of children with dyskinetic cerebral palsy (DCP).Methods:Sixty DCP children were randomly divided into a conventional intervention group, an RAGT group, and a combined intervention group, each of 20. All of the children received conventional rehabilitation therapy, while the RAGT and combined intervention groups were additionally provided with RAGT, and RAGT combined with TOT, respectively. Before the experiment and after 12 and 24 weeks of treatment, the subjects′ walking ability was evaluated using the 10-metre walk test (10MWT), and the D energy zone (standing position) and the E energy zone (walking, running and jumping) of the Gross Motor Function Measurement-88 (GMFM-88) instrument.Results:After 12 and 24 weeks of treatment, the average 10MWT speed and D and E energy zone scores of all three groups had improved significantly. After 24 weeks the combined group′s averages on all three measures were significantly better than those of the other two groups.Conclusion:RAGT combined with TOT and conventional rehabilitation training significantly improves the walking ability of DCP children.

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

Background: MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed. Methods: We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared. Results: Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM. Conclusion We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.