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.

Calciphylaxis, also known as calcific uremic arteriopathy (CUA), is a rare arteriosclerosis disease characterized by skin ischemia and necrosis with severe pain, which occurs in end-stage renal disease patients. The efficacy of sodium thiosulfate (STS) in CUA has been widely verified and affirmed. However, there is no unified standard for the use of STS at home and abroad.This article introduced a case of severe CUA patient who had achieved good results under different STS usage treatments, and summarized the different STS usage treatments for CUA combined with literature.

Objective To investigate the effect of Jiawei Simiao powder on the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway through miR-146a in monosodium urate(MSU)crystal-induced RAW264.7 macrophage inflammation models,and to explore its anti-inflammatory mechanism.Methods A cell model of gouty arthritis was established by inducing RAW264.7 cells with MSU crystals.Cells were divided into control,model,Jiawei Simiao powder,and colchicine groups and cell viability was assessed using the CCK-8 method.Levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.Expression levels of miR-146a miRNA and TLR4,myeloid differentiation factor 88(MyD88),TNF receptor-associated factor 6(TRAF6),and NF-κB p65 mRNA were detected by quantitative real-time polymerase chain reaction amplification technology,and protein expression levels of TLR4,MyD88,TRAF6,and phospho(p)-NF-κB p65 were evaluated by Western blot.Results miR-146a expression was significantly decreased in the model group compared with the control group(P＜0.01),while mRNA and protein expression levels of TLR4,MyD88,and TRAF6,and protein expression of p-NF-κB p65,IL-1β,IL-6,and TNF-α were significantly increased(P＜0.01).In contrast,miR-146a expression was significantly increased(P＜0.01)and mRNA and protein expression of TLR4,MyD88,and TRAF6,and p-NF-κB p65 protein expression(P＜0.01),as well as IL-1β,IL-6,and TNF-α levels(P＜0.05)were significantly decreased in the Jiawei Simiao powder and colchicine groups.Conclusions Jiawei Simiao powder may alleviate MSU crystal-induced macrophage inflammatory responses by upregulating miR-146a,suppressing TLR4/NF-κB signaling pathway activation,and decreasing secretion of inflammatory factors.

Objective To investigate the effect of Jiawei Simiao powder on the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway through miR-146a in monosodium urate(MSU)crystal-induced RAW264.7 macrophage inflammation models,and to explore its anti-inflammatory mechanism.Methods A cell model of gouty arthritis was established by inducing RAW264.7 cells with MSU crystals.Cells were divided into control,model,Jiawei Simiao powder,and colchicine groups and cell viability was assessed using the CCK-8 method.Levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were measured by enzyme-linked immunosorbent assay.Expression levels of miR-146a miRNA and TLR4,myeloid differentiation factor 88(MyD88),TNF receptor-associated factor 6(TRAF6),and NF-κB p65 mRNA were detected by quantitative real-time polymerase chain reaction amplification technology,and protein expression levels of TLR4,MyD88,TRAF6,and phospho(p)-NF-κB p65 were evaluated by Western blot.Results miR-146a expression was significantly decreased in the model group compared with the control group(P＜0.01),while mRNA and protein expression levels of TLR4,MyD88,and TRAF6,and protein expression of p-NF-κB p65,IL-1β,IL-6,and TNF-α were significantly increased(P＜0.01).In contrast,miR-146a expression was significantly increased(P＜0.01)and mRNA and protein expression of TLR4,MyD88,and TRAF6,and p-NF-κB p65 protein expression(P＜0.01),as well as IL-1β,IL-6,and TNF-α levels(P＜0.05)were significantly decreased in the Jiawei Simiao powder and colchicine groups.Conclusions Jiawei Simiao powder may alleviate MSU crystal-induced macrophage inflammatory responses by upregulating miR-146a,suppressing TLR4/NF-κB signaling pathway activation,and decreasing secretion of inflammatory factors.

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.

Calciphylaxis, also known as calcific uremic arteriopathy (CUA), is a rare arteriosclerosis disease characterized by skin ischemia and necrosis with severe pain, which occurs in end-stage renal disease patients. The efficacy of sodium thiosulfate (STS) in CUA has been widely verified and affirmed. However, there is no unified standard for the use of STS at home and abroad.This article introduced a case of severe CUA patient who had achieved good results under different STS usage treatments, and summarized the different STS usage treatments for CUA combined with literature.

【Objective】 To explore the surgical treatments and therapeutic outcomes for benign testicular tumor. 【Methods】 Clinical data of 53 patients with benign testicular tumor treated with surgery during May 2004 and Jul.2021 were retrospectively analyzed. 【Results】 The postoperative pathological diagnosis of 53 patients included 33 patients with epidermal cysts, 12 with mature teratomas, 2 with bilateral testicular tumors (one of them was epidermal cysts in the left and mature teratoma in the right, and the other was bilateral leiomyomas), and 6 benign cases. Testis sparing surgery (TSS) group had 23 patients and radical orchiectomy (RO) group had 30 patients. There were no significant differences in patients’ age, tumor location, disease course, and ultrasound examination results between the two groups (P>0.05). The tumor size of the RO group was (2.60±0.94) cm, which was larger than that of the TSS group (1.55±0.52) cm (P<0.001). There were no statistically significant differences in surgical time and postoperative hospital stay between the two groups (P>0.05). A total of 15 patients (13 with TSS and 2 with RO) underwent intraoperative frozen rapid pathological examination (FSA), which was consistent with post-operative paraffin pathological results. Durign the follow up of 2-219 months,median 38 months, there was no recurrence in either groups. 【Conclusion】 Testis sparing surgery is a reliable treatment modality for benign testicular tumor, which may also decrease the level of androgen and incidence of asthenozoospermia. It can be considered for tumors less than 2 cm with benign tendency or uncertain nature.

Objective To study the irradiation dose of organs at risk (OAR) in involved field radiation and extended field radiation in patients with thoracic esophageal cancer who received intensity modulated radiotherapy (IMRT). Methods A total of 40 patients with thoracic esophageal cancer were treated with IMRT. The involved field, extended field, and OAR were outlined to generate IMRT plans. The conformity index (CI) and homogeneity index (HI) of planning target volume (PTV) and the irradiation parameters of OAR were evaluated for the two plans. Paired t-test was used for comparison of irradiation parameters. Results The PTV of both plans received the prescribed dose. There were no significant differences in CI and HI of PTV between the two groups (P = 0.317, 0.130). There were significant differences in average lung dose, lung V₅, lung V₂₀, lung V₃₀, spinal cord D_mean, heart D_mean, heart D_max, heart V₃₀, heart V₄₀, and heart V₆₀ between the two groups (P < 0.01). Conclusion Compared with the extended field, the involved field can reduce the irradiation dose of ORA in patients with thoracic esophageal cancer, thus reducing the risk of radiation.

Objective: To explore the effects of ApoE epsilon4 (ApoE-ε4) alleles on cognitive function and resting-state functional MRI (rs-fMRI) in patients with amnestic mild cognitive impairment(aMCI) based on a prospective cohort study. Methods: An average of 20 months of prospective observations were conducted on 16 ApoE-ε4-carriers and 24 non-carriers of aMCI. Neuropsychological assessments and rs-fMRI data were collected at both baseline and follow-up. All participants were assessed by a battery of neuropsychological tests and underwent rs-fMRI. Two core regions of the default mode network (DMN), the left posterior cingulate cortex (PCC) and the medial prefrontal cortex (mPFC), were selected as seeds to calculate the functional connectivity. Two-way repeated measures analysis of variance was used to assess the effects of ApoE genotype(ε4-carriers, nonε4-carriers), interval and the interaction between these two factors for functional connectivity extracted from changed region found by t-test.Conversion rates of dementia were compared between ApoE-ε4-carriers and nonε4-carriers at follow-up using Chi-square test. For the comparison of functional connectivity and clinical data between ApoE-ε4-carriers and nonsε4-carriers in baseline and follow-up, the normal distribution test was carried out first. If the normal distribution was fitted, the two-sample t test was used, otherwise, the Mann-Whitney rank sum test was used. Finally, the general linear model was used to assess the relationships between alterations in functional connectivity and in neuropsychological assessments as well as the interaction effect. Results: (1)Significant decline in memory domains were found in ApoE-ε4-carriers as compared to non-carriers at both baseline and follow-up. The ApoE-ε4-carriers (14/16) presented a higher conversation rate than non-carriers(13/24, χ²=4.862, P=0.027) at follow-up. (2)Functional imaging analysis revealed that ApoE-ε4-carriers exhibited significantly higher functional connectivity between the left PCC and the left angular (ApoE-ε4-carriers: 0.23±0.11, non-carriers: -0.03±0.13, t=4.800, cluster size: 1 944 mm³, P=0.004), and between the left mPFC and the left angular (ApoE-ε4-carriers: 0.33±0.21, non-carriers: 0.08±0.18, t=5.040, cluster size:1 836 mm³, P=0.006) as compared to non-carriers at follow-up. We detected significant effect for the interaction interval by ApoE-ε4 on functional connectivity between the left angular and the left PCC (F=10.833, P=0.002)as well as the left mPFC (F=7.280, P=0.010). (3)The alteration of functional connectivity value between the left mPFC and the left angular in ApoE-ε4-carriers was positively correlated with the changes ofimmediate memory (r=0.692, P=0.018). The correlation was not statistically significant in ApoE-ε4-noncarriers (r=-0.198, P=0.417) and the integration effect was significant (F=8.632, P=0.006). Conclusions The ApoE-ε4 actually accelerates the deterioration of cognitive function in aMCI patients and carriers presented relatively reserved functional connectivity between the left angular and other core regions within DMN, which indicated the disruption of functional connectivity may be one of the underline mechanisms of ApoE-ε4 during AD process.

Objective To explore a new index for reflecting the topological information of brain functional networks in patients at high risk of Alzheimer disease using characteristics of resting-state functional connectivity strengths(FCS) in patients with amnestic mild cognitive impairment(aMCI). Methods Thirty-one aMCI patients and 42 age, gender and years of education matched normal controls were enrolled between September 2009 and April 2011 in this study. The resting-state functional MRI (rs-fMRI) data of all participants were acquired and preprocessed. Then the whole-brain functional connectivities were constructed for exploring the distribution characteristics of hub regions which had higher FCS values. Using two-sample t test to compare group differences in age, years of education and each neuropsychological assessment. In addition, using Chi-squared test to compare group differences in gender. Group differences in FCS values were analyzed by general linear model. Finally, correlation analyses were used to evaluate the relationships between the FCS values of the brain regions with group differences and behavioral scores in aMCI patients. Results The hub regions of the functional networks in the aMCI patients were mainly located in the association cortices such as the precuneuses, posterior cingulate cortices, medial prefrontal cortices, angular gyri, superior occipital gyri, fusiform gyri and lingual gyri. The distribution models in the aMCI patients were consistent with those in the normal controls. However, the FCS values of these brain regions were significantly lower in the aMCI patients than those in the normal controls. In comparison to the normal controls, the aMCI patients had significantly decreased FCS values in the bilateral fusiform gyri, lingual gyri, superior occipital gyri, left middle occipital gyrus and postcentral gyrus (the cluster was 389, 230, 187 and 107 voxels, respectively;P<0.05, respectively), and they had decreased trends of FCS values in the bilateral posterior cingulate cortices and right insulas. The correlation analysis with uncorrected conditions showed that the FCS values of the left postcentral gyri were correlatid with the clock drawing test (CDT) scores (r=0.436, P=0.026). Conclusions aMCI mainly attacks the hub regions of brain functional networks. The changes of functional connectivities in aMCI may reflect the early pathophysiologic alterations of AD.