Objective To analyze the characteristics of drug resistance in patients with disseminated pulmonary tuberculosis, and provide references for the clinical development of individualized treatment plans. Methods A retrospective analysis was conducted on 71 hospitalized patients with disseminated pulmonary tuberculosis treated at the Beijing Chest Hospital, Capital Medical University from January 2015 to January 2024. The susceptibility of Mycobacterium tuberculosis from these patients to 16 anti-tuberculosis drugs was detected using the microplate method for mycobacterial drug susceptibility testing. The study analyzed the culture results of Mycobacterium tuberculosis, drug susceptibility test results, initial treatment or re-treatment status, drug resistance, and differences in drug resistance types between initial and re-treated patients. Results Among the 71 patients with disseminated pulmonary tuberculosis, there were 51 males (71.8%), and 58 cases (81.7%) of acute disseminated pulmonary tuberculosis, with an overall drug resistance rate to 16 anti-tuberculosis drugs of 38.0%. There was no statistically significant difference in the total drug resistance rate between re-treated patients and those undergoing initial treatment [52.2%(12/23) vs. 31.3%(15/48), P=0.089]. The top 7 drugs to which patients were resistant were streptomycin (Sm) and isoniazid (INH) with 13 cases each (18.3%), rifapentine (Rft) and isoniazid aminosalicylate (Pa) with 10 cases each (14.1%), rifampicin (RFP), rifabutin (Rfb), and capreomycin (Cm) with 9 cases each (12.7%). The top 6 drugs to which initially treated patients were resistant were Cm with 6 cases (12.5%), Sm with 5 cases (10.4%), Pa with 4 cases (8.3%), INH, clarithromycin (Clr), and p-aminosalicylic acid (PAS) with 3 cases each (6.3%). The top 7 drugs to which re-treated patients were resistant were INH with 10 cases (43.5%), Sm, RFP, and Rft with 8 cases each (34.8%), Rfb with 7 cases (30.4%), Pa and levofloxacin (Lfx) with 6 cases each (26.1%). The overall mono-resistance rate, poly-drug resistance rate, and multidrug-resistant rate to 16 anti-tuberculosis drugs were 9.9%, 7.0%, and 11.3%, respectively; all mono-resistance patients were initially treated; there was no statistically significant difference in the poly-drug resistance rate between re-treated and initially treated patients (13.0% vs. 4.2%, P=0.591), but the multidrug-resistant rate was significantly higher in re-treated patients (30.4% vs. 2.1%, P=0.002). Conclusion Drug resistance in disseminated pulmonary tuberculosis is severe. Clinical physicians can develop personalized anti-tuberculosis treatment plans based on drug susceptibility test results.

Objective To investigate the value of CD66b⁺ tumor-associated neutrophils (TANs) and neutrophil to lymphocyte ratio (NLR) in evaluating the efficacy and prognosis of neoadjuvant chemotherapy (NACT) for breast cancer. Methods One hundred and sixty-seven patients of invasive breast cancer treated with NACT in the Department of Breast Surgery, the First People Hospital of Lianyungang from January 2015 to June 2020 were collected, and 40 cases of normal breast tissues were collected. Immunohistochemistry was used to detect the expression of CD66b in breast cancer tissues before NACT and normal breast tissues. Peripheral venous blood was taken from patients within 1 week before the first cycle of NACT, count neutrophils and lymphocytes were counted and their ratio (NLR) was calculated. The correlation between TANs and NLR and clinicopathologic features was analyzed by χ² test. The influencing factors of efficacy of NACT were analyzed by univariate χ² test and multivariate logistic analysis. Kaplan-Meier survival analysis and multivariate Cox analysis were used to determine the prognostic factors. The correlation between TANs and NLR was determined by Spearman test. Results The expression of CD66b in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.05), and it was diffusely distributed throughout the tumor (cancer nest and stroma were infiltrated). High infiltration of parenchymal TANs before NACT was correlated with high clinical stage, lymph node metastasis, and recurrence and metastasis (P<0.05). High NLR before NACT was closely related to high cT stage and recurrence and metastasis (P<0.05). NLR of peripheral blood (P=0.007), cT stage (P=0.041), estrogen receptor (ER) status (P=0.009), and human epidermal growth factor 2 (HER2) expression (P=0.020) were independent predictors for pathologic complete response (pCR). TANs (P=0.023), high clinical stage (P=0.040), and pCR (P=0.027) before NACT were independent risk factors for disease-free survival (DFS) of patients with invasive breast cancer. There was no correlation between NLR and TANs (r=0.14, P=0.071). Conclusions Low infiltration of parenchymal TANs before NACT predicts a better prognosis for patients with breast cancer. Higher NLR in peripheral blood is associated with chemotherapy resistance.

Objective To investigate whether axillary lymph node dissection (ALND) can be exempted for young breast cancers with reference to the inclusion criteria of American College of Surgeons Oncology Group (ACOSOG) Z0011 trial. Methods A retrospective analysis was conducted on 134 cases of young breast cancer patients admitted to the Second Affiliated Hospital of Nanchang University and the Affiliated Hospital of Jiujiang College from February 28, 2013 to February 28, 2018 who met the inclusion criteria of the ACOSOG Z0011 trial. Patients were divided into case group [n=63, with sentinel lymph node biopsy (SLNB)] and control group (n=71, with SLNB and ALND). General clinicopathologic data, including age, tumor TNM stage, pregnancy or breastfeeding status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, vessel carcinoma embolus, and tumor Nottingham grade, were collected and compared between the two groups. The 5-year disease-free survival (DFS) and 5-year overall survival (OS) of the two groups were analyzed using the Kaplan-Meier method with log-rank tests. A multifactorial Cox proportional hazards regression model was used to analyze the effect of SLNB implementation alone on the DFS and OS in young breast cancer. Results There were no statistically significant differences in age, pregnancy or breastfeeding status, tumor T classification, tumour molecular classification, tumor Nottingham grade and vessel carcinoma embolus between the two groups (P>0.05). The 5-year DFS rate for the 134 young breast cancer patients was 74.6% and the 5-year OS rate was 83.6%. A statistically significant difference was observed in the 5-year DSF rate between case and control groups (66.7% vs. 81.7%, P=0.033), while there was no statistically significant difference in the 5-year OS rate (77.8% vs. 88.7%, P=0.085). The multifactorial Cox proportional hazards regression model analysis showed that performing SLNB alone was an independent risk factor for DFS in young breast cancer patients (HR=2.261, 95%CI 1.097-4.660, P=0.027), but not for OS (HR=1.976, 95%CI 0.789-4.946, P=0.146). Conclusions Young breast cancers exempted from ALND according to the ACOSOG Z0011 trial inclusion criteria had a higher rate of local recurrence, but their OS was not significant affected. Therefore, whether young breast cancers can be exempted from ALND still requires further clinical trial validation.

Cushing's disease is a severe endocrine disorder caused by excess secretion of adrenocorticotropic hormone from pituitary. Due to its subtle early clinical manifestations , the diagnosis of Cushing's disease is often delayed, and differentiating it from ectopic adrenocorticotropic hormone syndrome is a challenge. Combined functional tests can improve the diagnostic accuracy of Cushing's disease. The primary treatment for Cushing's disease is surgical removal of pituitary adenoma. However, about 1/3 of patients do not respond or experience recurrence after surgery, necessitating second-line treatments including medication. The development of novel drugs has enhanced the role of pharmacotherapy in the management of Cushing's disease. The review discusses the classic and emerging diagnostic methods and treatment strategies of Cushing's disease to deepen clinicians' understanding of its current treatment status and prospects.

Objective To explore the clinical value of red blood cell volume distribution width coefficient of variation (RDW-CV), serum interleukin-11 (IL-11) and interleukin-31 (IL-31) in the diagnosis of interstitial lung disease (ILD). Methods Prospectively selected 46 ILD patients admitted to the Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Chengde Medical University from November 2022 to October 2023 were set as ILD group, 40 patients with community-acquired pneumonia (CAP) as CAP group, and 35 healthy examiners as control group. The ILD group was further divided into idiopathic interstitial pneumonia (IIP) subgroup (n=30) and connective tissue disease-related ILD (CTD-ILD) subgroup (n=16) based on clinical diagnosis. General and clinical data of each group were recorded, and RDW-CV and serum IL-11 and IL-31 levels were detected in each group. The ILD group was tested for alveolar arterial oxygen pressure difference (AaDO₂) and arterial blood oxygen pressure (PaO₂), and calculated the oxygenation index (OI). The correlation between the levels of RDW-CV, IL-11 and IL-31 and the severity of ILD were analyzed to explore the value of the above indicators in the clinical diagnosis of ILD and the differential diagnosis of different types of ILD. Results Compared with control group, there was no statistically significant difference in general information such as age, gender, smoking history, and complications between the ILD and CAP groups (P<0.05); RDW-CV, absolute values of neutrophil count (NEUT), and serum IL-11 and IL-31 levels in ILD group were significantly increased (P>0.05). Compared with CAP group, the levels of RDW-CV and serum IL-11, IL-31 in ILD group were increased, while the level of serum C-reactive protein (CRP) was decreased, with statistically significant differences (P<0.05). Correlation analysis results showed that RDW-CV and serum IL-31 in ILD patients were negatively correlated with OI (P<0.05), and positively correlated with AaDO₂ (P<0.05). The area under the ROC curves (AUC) of RDW-CV and serum IL-11, IL-31 single and combined applications for diagnosing ILD were 0.770, 0.666, 0.646, and 0.854, respectively (P<0.05). The AUC of serum IL-11 for differential diagnosis of CTD-ILD and IIP was 0.727(95%CI 0.580-0.874), with sensitivity of 62.5% and specificity of 73.3% (P<0.05). Conclusions RDW-CV and serum IL-31 have certain value in assessing the severity of ILD. RDW-CV and serum IL-11 and IL-31 have certain value in the diagnosis of ILD. Serum IL-11 has certain value in the differential diagnosis between CTD-ILD and IIP.

Objective To develop a matrix metalloproteinase (MMP)-responsive hyaluronic acid (HA)-based controlled-release material for brain-derived neurotrophic factor (BDNF) to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury (TBI). Methods HA was modified with amination, followed by condensation with Suflo-SMCC carboxyl group to form amide, and then linked with glutathione (GSH) to synthesize HA-GSH. The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF (GST-TIMP-BDNF) expression plasmid was constructed using molecular cloning technique with double enzyme digestion by BamH Ⅰ and EcoR Ⅰ. The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system, and purified by ion exchange chromatography, confirmed by Western blotting. MMP diluents were supplemented with PBS, MMP inhibitor marimastat, and varing concentrations (0.4, 0.6, 0.8 mg/ml) of GST-TIMP-BDNF or GST-BDNF. MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP. Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3. The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining. Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH. Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E. coli prokaryotic expression system. MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF (P<0.05). Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction (P<0.05). Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed, exhibiting a protective effect on neuron damage.

Sepsis-induced coagulopathy (SIC), a critical and potentially lethal condition arising from sepsis, results in endothelial damage and significant coagulation dysregulation, making it a major factor contributing to mortality among sepsis patients. Early diagnosis and treatment of SIC are expected to improve the prognosis of sepsis patients. In 2019, the International Society on Thrombosis and Hemostasis (ISTH) issued the first guidelines for the diagnosis and treatment of SIC, but there are no corresponding protocols in China. Therefore, Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association, and Chinese People's Liberation Army Professional Committee of Critical Care Medicine jointly formulated the "Chinese Expert Consensus on the Diagnosis and Treatment of Sepsis-induced Coagulopathy (2024 edition)." This consensus includes 5 parts: pathogenesis, classification, laboratory approaches, diagnosis and treatment, with a total of 14 evidence-based recommendations to guide clinical practice.

Refractory prolactinoma is the most common pituitary neuroendocrine tumor. Dopamine receptor agonists (DA) are the primary choice for drug treatment. Most patients with prolactinomas respond well to DA. However, a minority of prolactinomas patients still show resistance to DA. Although drug-resistant and refractory prolactinomas are rare in clinical practice, their treatment is extremely challenging. Even a combination of drug therapy, multiple surgeries, and radiotherapy may not yield satisfactory outcomes. Therefore, standardizing the diagnosis and treatment process and pathway for refractory prolactionmas and exploring more effective multidisciplinary collaborative treatment strategies are urgent problems to be solved. In the clinical management of refractory prolactinomas, it is often necessary to consider the patient's condition comprehensively, replace other types of DA, or consider surgery, radiotherapy, and immunotherapy, which requires multidisciplinary diagnosis and treatment. This review synthesizes the latest literature at home and abroad to systematically discuss the latest advances in drug therapy, surgery, and radiotherapy treatments for refractory prolactionmas, aiming to provide new ideas for basic research, clinical diagnosis and treatment.

Objective To investigate the role and underlying mechanism of miR-15b-5p on hypoxia/reoxygenation (H/R) induced human renal tubular epithelial cell (HK-2) injury by targeting forkhead box O1 (FOXO1). Methods HK-2 cells in the log growth phase were set up as follows: (1) control group (normal culture) and H/R group (H/R induced culture). The expressions of miR-15b-5p and FOXO1 mRNA were detected using qRT-PCR, and the protein expression of FOXO1 was detected using Western blotting. (2) Control group (normal culture), H/R group (H/R induced culture), H/R+mimic control group (cells transfected with mimic control then induced by H/R), H/R+miR-15b-5p mimic group (cells transfected with miR-15b-5p mimic then induced by H/R), H/R+miR-15b-5p mimic+OE-NC group (cells co-transfected with miR-15b-5p mimic and OE-NC plasmid, then induced by H/R), and H/R+miR-15b-5p mimic+OE-FOXO1 group (cells co-transfected with miR-15b-5p mimic and FOXO1 overexpression plasmid, then induced by H/R). The expression of miR-15b-5p was detected using qRT-PCR, and the protein expressions of FOXO1, cleaved caspase-3, Bax, and Bcl-2 were detected using Western blotting. CCK-8 assay was used to detect cell viability. Cell apoptosis was measured by the TUNEL method. (3) Control group (normal culture), H/R group (H/R induced culture), H/R+miR-15b-5p mimic group (cells transfected with miR-15b-5p mimic then induced by H/R), and H/R+miR-15b-5p mimic+OE-FOXO1 group (cells co-transfected with miR-15b-5p mimic and FOXO1 overexpression plasmid, then induced by H/R). The protein expressions of LC3, p62 and Beclin1 were detected using Western blotting. LC3 immunofluorescence was used to detect the cell autophagy. The target reaction between miR-15b-5p and FOXO1 was assessed using dual luciferase reporting assay. Results Under an inverted microscope, it was observed that the control group had a higher number of cells, most of which were in a typical cobblestone shape and grew in a cobblestone-like manner; most of the cells in the H/R group contracted and became round, with a significant decrease in the number of adherent cells. In H/R-induced HK-2 cells, miR-15b-5p was significantly down-regulated, while miRNA and protein expression of FOXO1 was up-regulated (P<0.05). Luciferase assay results showed that miR-15b-5p directly targeted the 3'-UTR of FOXO1. Overexpression of miR-15b-5p increased cell viability, reduced cell apoptosis, and decreased autophagy in H/R-induced HK-2 cells (P<0.05). Compared with H/R+miR-15b-5p mimic group, the viability of HK-2 cells was decreased, the apoptosis and autophagy level were increased in H/R+miR-15b-5p mimic+OE-FOXO1 group (P<0.05). Conclusion miR-15b-5p inhibited autophagy and alleviated H/R-induced HK-2 cell injury by targeting FOXO1.

Aneurysmal subarachnoid hemorrhage (aSAH), primarily caused by the rupture of intracranial aneurysms with bleeding into the subarachnoid space, is an acute neurological disease associated with high disability and mortality. Brain injury after aSAH results from a combination of injury mechanisms, with early brain injury (EBI) occurring within 72 hours post-onset, laying the foundation for subsequent pathophysiological changes in the brain and poor prognosis of patients. Among them, the brain immunoinflammatory response, involving the interaction of various immune cells and active substances, plays a significant role in post-aSAH EBI, and is related to delayed brain injury and long-term prognosis. Systemic inflammatory response following aSAH can also affect the prognosis and outcome of patients. This review summarizes the role of local and systemic immune inflammatory responses in the occurrence and progression of aSAH, as well as the research progress on related inflammatory biomarkers and therapeutic prospects, aiming to provide a theoretical reference for new treatment for aSAH.