Tuberculosis remains a prevalent and serious chronic bacterial infection worldwide. Despite significant advancements in TB treatment in recent years, it continues to pose a major public health challenge. The onset and progression of TB are closely associated with individuals who are immunocompromised, as most patients also present comorbidities such as HIV, diabetes mellitus, and nutritional deficiencies. Consequently, the development of new, non-toxic immunomodulatory drugs or treatment strategies may offer viable solutions to these issues. Vitamin D not only plays a crucial role in regulating calcium and phosphate metabolism while maintaining bone health but is also a key regulator of the innate immune response against microbial infections. Furthermore, many tuberculosis patients exhibit low levels of vitamin D; thus, vitamin D may represent an important resource for enhancing immune responses against Mycobacterium tuberculosis infections. This review discusses the immune response mechanisms, vitamin D synthesis processes, and metabolic pathways activated in hosts following infection with M. tuberculosis. It emphasizes how vitamin D contributes to immune regulation and its potential role in combating M. tuberculosis infections within the human body. This literature review aims to provide theoretical support for developing new drugs and treatment strategies for clinical management of anti-M. tuberculosis infections.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease characterized by progressive β-cell dysfunction and insulin resistance. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in T2DM management due to their ability to lower HbA1c, promote weight loss, and offer cardiovascular and renal protection. However, inter-individual variation in therapeutic response has been observed, potentially influenced by gut microbiota composition. A brief review was conducted to explore current evidence on the interaction between GLP-1RAs and gut microbiotatermed the "pharmaco-gut axis." Literature was examined to understand how specific microbial populations affect drug efficacy and insulin sensitivity. Studies suggest that certain gut microbes, including Bacteroides species, Akkermansia muciniphila, and those producing short-chain fatty acids (SCFAs), enhance GLP-1RA efficacy by improving insulin sensitivity and stimulating endogenous GLP-1 secretion. Conversely, dysbiosis characterized by reduced microbial diversity and increased lipopolysaccharide (LPS)-producing pro-inflammatory bacteria correlates with poor therapeutic response. Furthermore, GLP-1RAs may exert beneficial modulatory effects on the gut microbiota itself, indicating a bidirectional relationship. The interaction between GLP-1RAs and gut microbiota introduces a novel pharmaco-gut interface, emphasizing the role of microbial composition in drug response. This emerging concept has the potential to enhance precision medicine in diabetes care by utilizing microbiome profiling to guide GLP-1RA therapy and improve clinical outcomes.

We report a 55-year-old female who presented with choreiform movements in the right upper and lower limbs and uncontrolled blood sugar levels. Magnetic resonance imaging (MRI) of the brain revealed hyperdense lesions, without diffusion restriction or blooming on gradient echo, in the left lentiform and caudate nuclei. The clinical presentation and MRI brain findings pointed towards a diagnosis of diabetic striatopathy (DS). DS, an underrecognized and underdiagnosed condition, primarily affects older women with poorly-managed diabetes mellitus. Effective management of this disorder chiefly depends on maintaining optimal blood glucose levels. After rigorous glycemic control using insulin therapy, the patient's symptoms started to improve, achieving complete remission of symptoms in about a month.

The OMED2 (Optimization of Medication in Elderly with Diabetes) study addresses the effect and implementation of integrating a deprescribing programme (DPP) in general practice. The aim of the DPP is to reduce glucose-lowering medication (SU/insulin) in overtreated older patients. The protocol for this study has been published previously. This statistical analysis plan (SAP) contains a more elaborate outline of the (statistical) methods we plan to use for data analysis.

The OMED2 study is a randomized mixed-methods study with a 2-year follow-up period that compares the effect of the implementation of a DPP in general practice to regular care (control). In this SAP, we report on the (statistical) approaches that we plan to use to address the study objectives. The main objective of the OMED2 study is to examine the effect of the implementation of the DPP on diabetes complications, whereby the total number of diabetes complications related to undertreatment and overtreatment will be summed. Generalized linear mixed models with a Poisson distribution and the DPP as the main determinant will be used to test whether the total number of diabetes complications occurring from the start of the 2-year follow-up until the end of follow-up differs between intervention and control. The incident rate of the number of diabetes complications will be calculated to correct for possible differences in follow-up duration. The model will also include a random effect variable to allow for possible clustering effects by general practice. We will perform intention-to-treat analyses, which include all patients eligible for deprescribing, as well as per protocol analyses, which omit patients who were not deprescribed in the intervention arm. Additionally, approaches to study the implementation of the DPP and the cost-effectiveness of the implementation are outlined in the SAP.

ISRCTN Registry ISRCTN50008265. Registered on 1 November 2024.

Type 2 diabetes mellitus (T2DM) often induces diabetic osteoporosis (DOP) with impaired bone remodeling, yet its underlying mechanism remains elusive. This study identified the differential regulatory role of the AMPK/mTOR/p70 S6K signaling axis in bone cell function. In vivo, diabetes reduced AMPK phosphorylation, enhanced mTOR/p70 S6K activation, and diminished autophagy in rat femoral tissue. In vitro, HG exerted cell-type-specific effects via the AMPK signaling pathway: in osteoblasts, HG inhibited AMPK phosphorylation, activated mTOR/p70 S6K, suppressed autophagy, and impaired mineralization as well as alkaline phosphatase (ALP) activity; conversely, in osteoclasts, HG enhanced autophagy through the inverse regulatory pathway and accelerated osteoclast differentiation and bone resorption. Collectively, these findings illustrate that hyperglycemia disrupts bone homeostasis via cell-type-specific regulation of AMPK, suggesting that AMPK-mediated autophagy serves as a potential critical therapeutic target for diabetes-related bone diseases.

The optimal therapeutic strategy for patients with T2-3N0-3 M0 or T1N1-3 M0 hypopharyngeal squamous cell carcinoma (HPSCC) and the use of postoperative radiotherapy with or without systemic therapy for patients with T1-2N1M0 HPSCC remain controversial. We aimed to determine whether these additional treatments improve the prognosis in HPSCC.

We retrospectively analyzed the databases held by the SEER (surveillance, epidemiology, and end results) program and a tertiary referral center in China to evaluate the survival outcomes of surgical intervention for T2-3N0-3 M0 and T1N1-3 M0 HPSCC and of postoperative radiotherapy for T1-2N1M0 disease.

The SEER contained data for 1235 patients with T2-3N0-3 M0 or T1N1-3 M0 HPSCC, of whom 220 underwent surgery as their first treatment and 737 received non-surgical treatment. There was no statistically significant difference in overall survival (OS) between these two groups. Data were also available for 30 patients in the SEER who were treated by surgery alone (n = 11), surgery plus postoperative radiotherapy (n = 7), or surgery plus postoperative radiotherapy with systemic therapy (n = 12). Similarly, 23 patients at our hospital were identified to have been treated by surgery alone (n = 7), surgery plus postoperative radiotherapy (n = 10), or surgery plus postoperative radiotherapy with systemic therapy (n = 6). The SEER data indicated that postoperative radiotherapy improved OS (hazard ratio 0.281, 95% confidence interval 0.079-0.998; p = 0.036). This finding was supported by the data from our hospital, although the improvement in OS was not statistically significant (hazard ratio 0.360, 95% confidence interval 0.057-2.261; p = 0.224). Postoperative radiotherapy with systemic therapy seemed not to improve OS beyond that achieved by postoperative radiotherapy alone.

There was no significant difference in OS in patients with T2-3N0-3 M0 or T1N1-3 M0 HPSCC according to whether or not they underwent surgery as first-line treatment. Surgery plus postoperative radiotherapy was associated with a more favorable prognosis than surgery alone in patients with T1-2N1M0 HPSCC.

We aimed to, for the first time, assess the value of modified textbook outcome (mTO) in robot-assisted middle pancreatectomy (RMP) procedures.

Pancreatic fistula remains to be the major complication after RMP. Textbook outcome (TO) is introduced to capture the most desirable surgical outcomes. The value of TO in RMP surgery remains unknown.

All patients who underwent RMP in our center from 2010 to 2023 were enrolled in the study. Baseline characteristics, operative outcomes, and oncological outcomes were collected and analyzed. Textbook outcome was calculated separately for each patient and analyzed.

The mTO was defined by the absence of modified post-operative pancreatic fistula (mPOPF), postpancreatectomy hemorrhage (PPH), severe complications (Clavien-Dindo ≥ III), readmission, and in-hospital mortality (IHM). The overall mTO rate and mPOPF rate of 209 patients were 73.68% and 15.79%, respectively. Patients who achieved modified textbook outcomes have shorter post-operative hospitalization days (median (IQR), 17 (9) vs. 34 (26), p < 0.001). Passing the learning curve leads to a reduction of the mPOPF rate and an increase of the mTO rate.

Modified textbook outcome is a practical metric for evaluating ideal surgical outcomes in RMP surgery. Follow-up multi-center clinical research is necessary to evaluate this indicator even further.

The present investigation was designed to assess the prognostic value of microRNA-648 (miR-648) in osteosarcoma (OS) and elucidate its regulatory mechanisms. Quantitative real-time PCR was employed to measure miR-648 expression levels in 80 paired OS specimens and their matched adjacent non-tumor tissues. Statistical assessments of clinical parameters were conducted using Chi-squared tests, while patient survival data were evaluated through Kaplan-Meier estimation and Cox proportional hazards regression modeling. Functional assays were performed in OS cell lines. Bioinformatic prediction of target genes was followed by experimental validation using dual-luciferase reporter assays. MiR-648 exhibited significant downregulation in OS clinical specimens and cell lines (p < 0.001). Low miR-648 expression correlated with lung metastasis (p = 0.027), advanced Enneking stage (p = 0.031), and poorer progression-free survival (p < 0.001). MiR-648 was identified as a significant independent prognostic indicator (hazard ratio [HR] = 0.235, p < 0.001). Moreover, the overexpression of miR-648 significantly suppressed cellular proliferation, migration capacity, and invasion potential while enhancing apoptotic activity (p < 0.001). High mobility group box 1 (HMGB1) was confirmed as a direct target, with its role in reversing miR-648's tumor-suppressive effects. MiR-648 exerts tumor-suppressive effects in OS by modulating HMGB1, suggesting its clinical utility as both a prognostic biomarker and a therapeutic intervention point.

Female urethral adenocarcinoma (FUA) is an exceptionally rare and aggressive malignancy, accounting for less than 0.02% of all cancers in women. Its nonspecific symptoms often lead to delayed diagnosis, with many cases detected at advanced stages. The rarity of FUA, particularly when presenting with a large mass, underscores the challenges in developing standardized treatment protocols.

A 65-year-old woman presented with urinary retention. Clinical examination revealed a large mass obstructing the urethral orifice. A computed tomography (CT) scan showed a malignant mass involving the entire length of urethra, with no signs of metastasis. Percutaneous cystostomy was performed, and cystoscopy through the cystostomy access revealed tumor infiltration into the anterior bladder wall, approximately 2 cm from the bladder neck. A radical urethrectomy with partial cystectomy and bladder outlet reconstruction was performed via a transurethral approach, with antegrade cystoscopy guidance. The bladder outlet was reconstructed using a segment of the anterior bladder wall to facilitate voiding through the orthotopic site with a Foley catheter. Pathology confirmed pT4 urethral adenocarcinoma with enteric subtype and clear surgical margins. Neither radiation nor chemotherapy was administered. At the 1-year follow-up, the patient was in continuous incontinence status. This condition is expected since the sphincter was also resected during the surgery as the tumor already infiltrated the anterior bladder. But with the use of silicone catheter, we can avoid any leak and patient still can void timely through regularly clamp catheter. At the 1-year follow-up, the patient reported satisfaction with her quality of life and showed no signs of recurrence or metastasis.

This case highlights the feasibility of bladder-preserving surgical techniques in giant FUA with bladder infiltration. The approach achieved oncological control while maintaining the patient's quality of life. Bladder outlet reconstruction provided satisfactory functional outcomes and eliminated the need for suprapubic urinary diversion.