Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

OBJECTIVE:With the popularity of simulated barefoot running,minimalist shoes have become a new way of foot exercise.As an important muscle group of the foot,the maintenance of foot muscle morphology is important for the execution of foot functions.In this paper,by combing the literature about the effect of minimalist shoes on foot muscle morphology in recent years,we systematically evaluate the effect of minimalist shoes on foot muscle morphology compared with traditional running shoes. METHODS:The relevant articles published from 2012 to 2022 were searched in Chinese and English databases(PubMed,Web of Science,ProQuest,CNKI and WanFang databases)with"minimal shoes,minimal footwear,minimalist shoes,minimalist footwear,foot muscle,feet muscle"as Chinese and English keywords,respectively.Meta-analysis,sensitivity tests were performed on the included literature using Review Manager 5.4.1 and Stata 14 software,the Egger method was used to test for publication bias in the literature,and Meta-regression was used to identify the subgroups with heterogeneity. RESULTS:Compared with traditional running shoes,minimalist shoes increased muscle circumference of the abductor hallucis[standardized mean difference=2.034,95%confidence interval(1.192,2.877),Z=4.73,P＜0.001].And the results were not reversed after clipping and patching,with a more robust combined effect size(P＜0.05).For the toe short flexors,the total combined effect size did not show a difference between traditional running shoes and minimalist shoes[standardized mean difference=0.470,95%confidence interval(-0.45,1.39),Z=1.00,P=0.318]. CONCLUSION:Compared with traditional running shoes,minimalist shoes intervention can effectively improve muscle circumference of the abductor hallucis,but the promoting effect on the flexor digitorum brevis muscle is not obvious.Running in minimalist shoes has positive implications for the maintenance of the medial longitudinal arch,but it is necessary to enrich the research content of minimalist shoes on different foot muscles and different populations in order to further explore the mechanisms by which minimalist shoe interventions promote foot function.

Objective·To observe the effects of gingipain extract on the biological characteristics of oral squamous cell carcinoma cell HN6.Methods·The HN6 cell line was selected,cultivated,and divided into different groups based on the protein concentration of gingipain extract from Porphyromonas gingivalis:control group,3.125 μg/mL group,6.25 μg/mL group,12.5 μg/mL group,25 μg/mL group,50 μg/mL group,and 100 μg/mL group.After 24 and 48 h of cultivation,CCK-8 assay was used to detect the effects of gingipain extract on HN6 cell proliferation activity.Subsequent experiments were divided into control group,25 μg/mL group and 50 μg/mL group.Flow cytometry was used to examine the effects of gingipain extract on cell cycle.Scratch assay and Transwell assay were performed to evaluate cell migration and invasion ability.Real-time PCR(RT-PCR)and Western blotting were used to measure the expression of E-cadherin and N-cadherin proteins and genes in cells.Results·Stimulated with gingipain extract for 24 h,the HN6 cells showed significantly increased proliferation activity in the 25 μg/mL(P=0.025),50 μg/mL(P=0.000),and 100 μg/mL(P=0.049)groups compared to the control group.After 48 h,proliferation activity was significantly higher in the 6.25 μg/mL(P=0.024),12.5 μg/mL(P=0.006),25 μg/mL(P=0.000),50 μg/mL(P=0.000),and 100 μg/mL(P=0.000)groups compared to the control group.Cell cycle analysis revealed that,after 24 h of gingipain stimulation,the proportion of HN6 cells in the G1 phase decreased,while the proportion in the S+G2 phase significantly increased compared to the control group(25 μg/mL group:P=0.024;50 μg/mL group:P=0.001).Compared to the control group,the scratch assay demonstrated a significant increase in the percentage of scratch closure as the concentration of gingipain extract increased(P=0.001).Compared to the control group,the Transwell invasion assay showed a significant increase in the number of cells passing through the bottom of the chamber as the concentration of gingipain extract increased.RT-PCR and Western blotting results indicated that as the concentration of gingipain extract increased,the expression levels of N-cadherin mRNA and protein in HN6 cells significantly increased,while the expression levels of E-cadherin mRNA and protein significantly decreased compared to the control group.Conclusion·Gingipain extract could promote proliferation,migration,and invasion of oral squamous cell carcinoma HN6 cells.

Objective:To observe the outcome of posterior staphyloma (PS) marginal retinal photocoagulation in pars plana vitrectomy (PPV) for high myopia macular hole retinal detachment eyes accompanied with PS.Methods:From January 2017 to June 2019, 49 patients (49 eyes) with high myopia macular hole retinal detachment accompanied with PS who were undergone PPV operation from Tianjin Eye Hospital were included in this study. There were 13 males (13 eyes) and 36 females (36 eyes). All patients underwent best corrected visual acuities (BCVA) and optical coherence tomography examinations. The standard logarithmic visual acuity chart was used for BCVA examination, and the visual acuity was converted to minimum resolution angle in logarithmic (logMAR) when recorded. The patients were randomly divided into two groups according to surgical options: conventional PPV with internal limiting membrane (ILM) peeling (group A, 24 eyes), PS marginal retinal photocoagulation in PPV with ILM peeling (group A, 25 eyes). The mean preoperative logMAR BCVA of group A and B were 1.87±0.28 and 1.80±0.37, the difference was not statistically significant ( t=0.604, P=0.551). The patients in the group A received 23G PPV, triamcinolone acetonide staining during the operation, the epiretinal membrane was peeled off, indocyanine green assisted staining, the posterior macular ILM was peeled off, and the peripheral retina was examined in detail during the operation. Areas with retinal degeneration were reinforced by laser photocoagulation, and the subretinal fluid was drained through the macular hole and filled with silicone oil. The eyes of the group B were subjected to retinal photocoagulation for 2 to 3 rows at the edge of the PS in addition to the usual surgical procedures. The average follow-up time was 8.34±3.21 months. Surgical outcome were estimated by the average number of operation, retinal reattachment rate, macular hole closure rate and BCVA. The χ2 test or Fisher exact probability was used to compare the count data. Independent sample t test was used to compare the measurement data. Results:Retinal reattachment was obtained in 17 eyes (70.8%, 17/24) and 24 eyes (96.0%, 24/25) in group A and B after first surgery respectively, the difference was statistically significant ( χ2=3.984, P=0.046). Final retinal reattachment was obtained in all 49 eyes. Final macular hole closure was in 15 eyes (62.5%, 15/24) and 19 eyes (76.0%, 19/25) in group A and B, respectively, the difference was not statistically significant ( χ2=1.051, P=0.305). The mean postoperative logMAR BCVA of group A (1.20±0.47) and B (1.08±0.39) were all improved than preoperative BCVA, the differences were all statistically significant ( t=2.899, 5.327; P=0.001, 0.000), the differences of mean postoperative logMAR BCVA between two groups was not statistically significant ( t=0.675, P=0.506). The mean number of operation of group A (2.63±0.88) was more than group B (2.08±0.28), the difference was statistically significant ( t=3.003, P=0.006). Conclusion:In comparison with conventional PPV, combined PS marginal retinal photocoagulation can improve retinal reattachment rate after first surgery, and reduce the number of reoperations.

Objective:To observe the changes of macular microvessels in patients with retinal vein occlusion (RVO) and macular edema (ME) after intravitreal injection of aflibercept (IVA), and analyze its correlation with best corrected visual acuity (BCVA).Methods:A retrospective case study. Thirty patients (30 eyes) with monocular RVO with ME (RVO-ME) who were diagnosed in the clinical examination of Tianjin Eye Hospital from April 2019 to February 2020 were included in the study. Among them, there were 12 males (12 eyes) and 18 females(18 eyes); the average age was 54.30±13.17 years. The average course of disease was3.43±1.97 months. Both eyes were examined by BCVA and optical coherence tomography (OCTA). The on-demand injection was adopted after the first injection in IVA treatment regimen. The macular area 6 mm×6 mm in both eyes was scanned with an OCTA instrument, and the area of the foveal avascular area (FAZ), FAZ circumference (PERIM), and out-of-roundness were measured at baseline and 1, 3, and 6 months after treatment. Index (AI), blood flow density within 300 μm width of FAZ (FD-300), foveal retinal thickness (CMT), superficial retinal capillary plexus (SCP), deep retinal capillary plexus (DCP) blood flow density. The paired t test was used to compare the quantitative parameters of the affected eye and the contralateral healthy eye at baseline; the changes of the quantitative parameters at baseline and 1, 3, and 6 months after treatment were analyzed by repeated measures analysis of variance. Pearson correlation analysis was used to analyze the correlation between BCVA, retinal perfusion, and macular blood supply parameters at 6 months after IVA treatment. Results:At baseline, compared with the contralateral healthy eye, the FAZ area ( t=-4.091), PERIM ( t=-5.098) and AI ( t=-9.093) of the RVO-ME eye were enlarged, and FD-300 ( t=7.237) and overall SCP and DCP blood flow density ( t=8.735, 9.897) decreased, the difference was statistically significant ( P<0.001). Six months after treatment, the BCVA of RVO-ME eyes was significantly increased, CMT decreased, FAZ area expanded, and AI decreased ( t=8.566, 16.739, -6.469, 9.719; P<0.001), the difference was statistically significant. There was no significant change in the blood flow density of FD-300 and overall SCP and DCP, and the difference was not statistically significant ( t=1.017, 1.197, 0.987; P>0.05). Compared with baseline, the FAZ area of RVO-ME eyes gradually expanded at 3 and 6 months after treatment, and the difference was statistically significant ( F=21.979, P<0.001). Correlation analysis results showed that BCVA at 6 months after treatment was positively correlated with the overall SCP and DCP blood flow density at baseline and 6 months after treatment ( r=-0.538, -0.484, -0.879, -0.854; P<0.05). There was a negative correlation with the area of FAZ 6 months after treatment ( r=0.544, P=0.001). The number of ME recurrences was negatively correlated with BCVA and overall SCP and DCP blood flow density 6 months after treatment ( r=0.604, -0.462, -0.528; P<0.05), it was positively correlated with FAZ area ( r=0.379, P=0.043). Conclusion:Within 6 months of IVA treatment in RVO-ME eyes, ME is significantly reduced and visual acuity is improved; SCP blood flow density decreases, and FAZ area expands.

Objective:To compare the application of epidural analgesia (EA) with intravenous analgesia (IA) in radical gastrectomy for gastric cancer.Methods:A systematic review and meta-analysis of randomized controlled trials of EA and IA in radical gastrectomy was conducted. Primary outcome was pain scores at 24 h after surgery, while the secondary outcomes included incidence of postoperative complications, first flatus time and (LOS).Results:A total of 6 randomized controlled studies was identified and 393 patients were enrolled in this review, 4 published in English and 2 in Chinese. Meta-analysis revealed that, the EA group had lower pain score at 24h either pain at rest ( WMD=-0.74, 95% CI: -1.35~-0.13, P=0.02) or pain on movement or coughing( WMD=-1.5, 95% CI: -1.95~-1.05, P<0.001) than that of the IA group. In terms of complications, postoperative nausea and vomiting ( RR=0.32, 95% CI: 0.18~0.58, P<0.001) and respiratory complications ( RR=0.50, 95% CI: 0.29~0.85, P=0.01) in EA group were obviously lower than those of the IA group. No difference was observed in postoperative urinary complications between the two groups ( RR=0.87, 95% CI: 0.38~1.96, P=0.73). However, the incidence of hypotension was obviously higher than that of IA group ( RR=3.27, 95% CI: 1.28~8.32, P=0.01). Time of first exhaust time after operation ( WMD=-14.01, 95% CI: -22.85~-5.17, P=0.002), postoperative length of hospital stay ( WMD=-0.69, 95% CI: -0.90~-0.49, P<0.001) were shorter than IA group. Conclusions:For patients who undergoing radical gastrectomy for gastric cancer, epidural analgesia could provide better pain control either pain at rest or on movement, although a rising incidence of hypotension was leaded, reduced pulmonary complications, nausea and vomiting were found, and promote the bowel function and shorten the duration of hospital stay.

Objective: To understand the mortality and influencing factors on injecting drug users (IDUs) with HIV/AIDS, in Guizhou province, 1996-2015. Methods: A retrospective cohort study was conducted on IDUs with HIV/AIDS that were reported through national comprehensive HIV/AIDS information system, in Guizhou province during 1996-2015. Cox proportional hazard regression model was used to analyze the influencing factors on the mortality of HIV/AIDS. Results: A total of 3 958 cases of IDUs with HIV/AIDS were recruited in this study, with all-cause mortality rate of 44.01% (1 742/3 958) and total mortality rate of 7.80/100 person-years, respectively. The median survival time between diagnosis and death was 8.08 years. Mortality rate was 3.57/100 person-years in the group receiving antiretroviral therapy (ART). The mortality appeared to be 4.08/100 person-years in the group who were on methadone maintenance treatment (MMT). Data from the multiple regression analysis indicated that factors of gender, ethnicity, age when HIV/AIDS diagnosis was made, CD₄⁺T lymphocyte (CD₄) count at the first testing, ART and MMT were significantly associated with deaths among these people. The risk of death in females was 0.82 times (95%CI: 0.69-0.98) higher than that in males. The risk of deaths among the ethnic minority subjects was 1.39 times (95%CI: 1.21-1.60) higher than that of the Hans. The risk of death appeared to be 2.44 times higher (95%CI: 1.07-5.56) in the over-50-year of age group than in the <20 year-old group, when HIV/AIDS was diagnosed for the first time. The risk of death in CD₄ ≥500/μl group in the first time was 0.27 times (95%CI: 0.22-0.32) more than CD₄ <200/μl group in the firs time. The risk of death in cases who were treated with ART or MMT was 2.83 times (95%CI: 2.45-3.26) and 1.35 times (95%CI: 1.15-1.59) higher than those who did not receive any treatment, respectively. Conclusion Higher risks on death seemed to be related to the following factors: being male, older age at the time of diagnosis, lower CD₄ at diagnosis, not on ART or MMT among the IDUs with HIV/AIDS in Guizhou province, between 1996-2015.

Exoskeleton nursing robot is a typical human-machine co-drive system. To full play the subjective control and action orientation of human, it is necessary to comprehensively analyze exoskeleton wearer's surface electromyography (EMG) in the process of moving patients, especially identifying the spatial distribution and internal relationship of the EMG information. Aiming at the location of electrodes and internal relation between EMG channels, the complex muscle system at the upper limb was abstracted as a muscle functional network. Firstly, the correlation characteristics were analyzed among EMG channels of the upper limb using the mutual information method, so that the muscle function network was established. Secondly, by calculating the characteristic index of network node, the features of muscle function network were analyzed for different movements. Finally, the node contraction method was applied to determine the key muscle group that reflected the intention of wearer's movement, and the characteristics of muscle function network were analyzed in each stage of moving patients. Experimental results showed that the location of the myoelectric collection could be determined quickly and efficiently, and also various stages of the moving process could effectively be distinguished using the muscle functional network with the key muscle groups. This study provides new ideas and methods to decode the relationship between neural controls of upper limb and physical motion.
Electromyography ; Exoskeleton Device ; Humans ; Muscle, Skeletal ; physiology ; Robotics ; Upper Extremity