Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Objective To evaluate the impact of Jixiong Jiedu decoction on the efficacy of diabetic kidney disease in mice and its influence on intestinal flora and trimethylamine oxide(TMAO)levels.Methods Twelve 7-week-old male db/db mice were randomly assigned to the model group or Jixiong Jiedu decoction group(6 mice per group),while 6 male db/m mice were designated as the control group.Following 8 weeks of continuous gavage,we monitored the body weight and blood glucose levels of the mice at weeks 0,4,and 8.Additionally,we assessed urinary microalbumin,kidney injury molecule-1(KIM-1),creatinine(Scr),and urea nitrogen(BUN)levels in urine.Renal pathology was evaluated using HE and PAS staining.Furthermore,fecal samples underwent 16s RNA sequencing,and the serum TMAO levels were determined.Results Compared with the control group,the blood glucose,body weight,8-hour urinary microalbumin,KIM-1 and Scr in the model group were significantly increased,and the renal pathology showed that glomerular segmental mesangial matrix increased,glomerular volume hypertrophy and renal tubular epithelial cell swelling.The abundance of Lactobacillaceae and Lactobacillus in the model group was significantly increased(P<0.01).The abundance of Lachnospiraceae,Helicobacter and Oscillospira decreased significantly(P<0.01),the abundance of each bacterial group changed,and the serum TMAO content increased significantly.Compared with the model group,the 8h urinary microalbumin,KIM-1(P<0.01)and Scr(P<0.05)in the Jixiong Jiedu decoction group were significantly decreased,and there was no significant difference in BUN(P>0.05),and the renal pathological damage was significantly improved.The abundance of Lactobacillaceae and Lactobacillus in intestinal flora decreased significantly(P<0.01),while the abundance of Lachnospiraceae and Oscillospira increased significantly(P<0.01,P<0.05).The structure of gut microbiota,the abundance of dominant and non-dominant bacteria were positively adjusted,and the serum TMAO content was significantly decreased(P<0.01).Conclusion Jixiong Jiedu decoction effectively ameliorates intestinal flora disorders in db/db mice and regulates serum TMAO levels,thereby exerting a nephroprotective effect.

Immunotherapy has demonstrated significant efficacy in hematologic malignancies and certain solid tumors,but its efficacy for prostate cancer remains suboptimal.This is largely due to the immunosuppressive tumor microenvironment,which involves factors such as tumor heterogeneity,a paucity of infiltrating lymphocytes,and the absence of inflammatory features.Therefore,developing novel immunotherapeutic targets and combining multiple immunotherapy modalities to activate the host immune system and reverse the immunosuppressive tumor microenvironment are crucial for improving immunotherapy for prostate cancer.This review systematically summarizes the current research on prostate cancer immunotherapy,covering the challenges and advances of prostate cancer vaccines,the application of immune checkpoint inhibitors,targeted therapeutic strategies involving chimeric antigen receptor T cells,bispecific antibodies,and emerging strategies in prostate cancer immunotherapy.Furthermore,the review discusses the future directions for the development of prostate cancer immunotherapy.

Immunotherapy has demonstrated significant efficacy in hematologic malignancies and certain solid tumors,but its efficacy for prostate cancer remains suboptimal.This is largely due to the immunosuppressive tumor microenvironment,which involves factors such as tumor heterogeneity,a paucity of infiltrating lymphocytes,and the absence of inflammatory features.Therefore,developing novel immunotherapeutic targets and combining multiple immunotherapy modalities to activate the host immune system and reverse the immunosuppressive tumor microenvironment are crucial for improving immunotherapy for prostate cancer.This review systematically summarizes the current research on prostate cancer immunotherapy,covering the challenges and advances of prostate cancer vaccines,the application of immune checkpoint inhibitors,targeted therapeutic strategies involving chimeric antigen receptor T cells,bispecific antibodies,and emerging strategies in prostate cancer immunotherapy.Furthermore,the review discusses the future directions for the development of prostate cancer immunotherapy.

Hydrogen-rich water (HRW) shows excellent antibacterial, anti-inflammatory, antioxidant, and wound-healing properties and plays a positive role in the treatment of various diseases, such as brain injury, kidney injury, and periodontitis. Current studies found that HRW can inhibit periodontopathogenic biofilm formation, inhibit oral connective tissue and bone tissue destruction, and show anti-inflammatory and antioxidant properties in periodontitis. Additionally, HRW can alleviate periodontal tissue damage by inhibiting oxidative stress and up-regulating the expression of antioxidant enzymes, such as glutathione peroxidase and superoxide dismutase. HRW exerts anti-inflammatory effects by regulating the nuclear factor erythroid 2-related factor 2 and mitogen-activated protein kinase pathways, which are closely associated with inflammation. Additionally, HRW inhibits the expression of inflammatory cytokines, such as interleukins, inhibits the growth and proliferation of bacterial plaque biofilms, and down-regulates glycosyltransferases and glucan-binding proteins to prevent bacterial adhesion and subsequent development of periodontitis. Furthermore, HRW has a positive effect on the expression of various cell growth factors, α-smooth muscle actin, and type I collagen, which promotes wound healing. Current clinical studies have demonstrated the biological safety of HRW (to a certain extent) and reported no adverse reactions. However, most studies on HRW in oral diseases are preclinical in vivo and in vitro studies. Therefore, further clinical studies are required to validate the therapeutic significance and optimal therapeutic regimen of HRW in human periodontitis. This article aims to review the therapeutic role and the underlying mechanisms of HRW in periodontitis.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Objective:To summarize and analyze the clinical efficacy and experience of ultrasound-guided radiofrequency ablation (RFA) in the treatment of Kasabach-Merritt syndrome (KMS).Methods:A retrospective analysis was conducted on the data of pediatric patients with KMS who underwent ultrasound-guided RFA in Department of Hemangioma Surgery, the Third Affiliated Hospital of Zhengzhou University, between March 2018 and March 2024. Preoperative laboratory tests and imageological examination were performed. Under general anesthesia, the working tip of the RFA electrode needle was precisely reached the bottom of the lesion under ultrasound guidance. The electrode needle was then gradually withdrawn until the entire lesion area was covered by hyperechoic signals, indicating complete ablation. Postoperative symptomatic and supportive treatments, such as ice pack application and dressing changes, were administered to the surgical area. Platelet detection was performed immediately after the operation. Complications were closely monitored and regular follow-ups were carried out.Results:A total of 30 pediatric patients were included, comprising 14 males and 16 females, from 10 min to 5 months and 29 d after birth, with a median time of 6 d. Lesions were located in the limbs and trunk in 27 cases, and head and neck region in 3 cases, with lesion volumes ranged from 2.4 cm×2.3 cm×1.2 cm to 14.4 cm×9.3 cm×3.3 cm. The mean preoperative platelet count was 43×10 9/L, among them, the platelet values of 11 cases were (10-30) ×10 9/L, and those of 6 cases were lower than 10×10 9/L, other 13 cases with progressive thrombocytopenia. All patients successfully underwent RFA, achieving complete lesion ablation and normalization of platelet counts postoperatively. Platelet counts recovered to above 300×10 9/L in 15 patients, with no severe complications observed. The RFA area became slightly hardened within 7 d postoperatively but gradually returned to normal after consistent dressing changes for 2 weeks. During the follow-up period of 6 months to 2 years, complete lesion ablation was confirmed, with disappearance of the mass, no recurrence, good local function, mild local scar formation, and satisfactory cosmetic appearance. Conclusion:Ultrasound-guided RFA for KMS has advantages of favorable therapeutic outcomes, minimal tissue damage, no significant complications, and satisfactory cosmetic result.

BACKGROUND:There is a central sensitization mechanism for lumbar disc herniation-specific pain sensitization,and it is unclear whether cyclic RNAs in the paraventricular nucleus brain region are involved in lumbar disc herniation-specific pain sensitization.OBJECTIVE:To investigate the mechanism by which cyclic RNA circ05188 in the paraventricular nucleus of rats with lumbar disc herniation regulates the participation of microRNAs in pain sensitization.METHODS:Fifty-two Sprague-Dawley rats were randomly divided into a sham operation group,a lumbar disc herniation group,a knockdown control group and a circ05188 knockdown group,with 13 rats in each group.Except for the sham operation group,the lumbar disc herniation model was established in the other three groups.On the 7th day after modeling,the hypothalamic paraventricular nucleus of the knockdown control group and circ05188 knockdown group were injected with siRNA-NC and siRNA-circ05188,respectively,at 1 day intervals,for a total of three injections.On the 7th day after modeling,high-throughput sequencing technology was used to detect the expression of differential circRNAs in the hypothalamic paraventricular nucleus of rats in the sham operation group and the lumbar disc herniation group,and RT-qPCR was used to detect the expression of circ05188 and miR-199a-5p in the hypothalamic paraventricular nucleus.On the 3rd,7th,14th,21st,and 28th days after modeling,we detected the mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot in the modeled side of rats in the sham operation group and the lumbar disc herniation group.On the 3rd day after siRNA injection,immunofluorescence staining was used to detect the expression of c-Fos in the hypothalamic paraventricular nucleus of rats in the knockdown control group and circ05188 knockdown group;RT-qPCR was used to detect the expression of circ05188 and miR-199a-5p in the hypothalamic paraventricular nucleus of rats in the knockdown control group and circ05188 knockdown group;on the 5th day after siRNA injection,mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot were detected in the knockdown control group and circ05188 knockdown group.Bioinformatics analysis and dual luciferase reporter elucidated the underlying molecular mechanism of circ05188 in pain sensitization after lumbar disc herniation.RESULTS AND CONCLUSION:High-throughput sequencing results showed that circRNAs were differentially expressed in the paraventricular nucleus brain region of rats with lumbar disc herniation.The expression of circ05188 was higher in the lumbar disc herniation group than in the sham operation group(P<0.05),the expression of miR-199a-5p was lower than in the sham operation group(P<0.05),and the mechanical and thermal mechanical paw withdrawal thresholds of the hindfoot were lower than those of the sham operation group at 3,7,14,and 21 days after modeling.RT-qPCR results showed that compared with the knockdown control group,the expression of c-Fos and circ05188 was lower in the circ05188 knockdown group(P<0.05),while the expression of miR-199a-5p was higher(P<0.05).The mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot in the circ05188 knockdown group were higher than those in the knockdown control group at 1,2,and 3 days after injection.Bioinformatics analysis and dual luciferase reporter assay results showed that miR-199a-5p had a binding site with circ05188 and circ05188/miR-199a-5p competitive endogenous RNA axis.To conclude,lumbar disc herniation induces an increase in circ05188 expression in the paraventricular nucleus of the hypothalamus,which produces central sensitization through the inhibition of miR-199a-5p and ultimately triggers neuropathic pain.

OBJECTIVE: To investigate the spatiotemporal patterns and socioeconomic factors influencing the incidence of tuberculosis (TB) in the Guangdong Province between 2010 and 2019. METHOD: Spatial and temporal variations in TB incidence were mapped using heat maps and hierarchical clustering. Socioenvironmental influencing factors were evaluated using a Bayesian spatiotemporal conditional autoregressive (ST-CAR) model. RESULTS: Annual incidence of TB in Guangdong decreased from 91.85/100,000 in 2010 to 53.06/100,000 in 2019. Spatial hotspots were found in northeastern Guangdong, particularly in Heyuan, Shanwei, and Shantou, while Shenzhen, Dongguan, and Foshan had the lowest rates in the Pearl River Delta. The ST-CAR model showed that the TB risk was lower with higher per capita Gross Domestic Product (GDP) [Relative Risk ( RR), 0.91; 95% Confidence Interval ( CI): 0.86-0.98], more the ratio of licensed physicians and physician ( RR, 0.94; 95% CI: 0.90-0.98), and higher per capita public expenditure ( RR, 0.94; 95% CI: 0.90-0.97), with a marginal effect of population density ( RR, 0.86; 95% CI: 0.86-1.00). CONCLUSION The incidence of TB in Guangdong varies spatially and temporally. Areas with poor economic conditions and insufficient healthcare resources are at an increased risk of TB infection. Strategies focusing on equitable health resource distribution and economic development are the key to TB control.
Humans ; China/epidemiology* ; Incidence ; Bayes Theorem ; Spatio-Temporal Analysis ; Tuberculosis/epidemiology* ; Socioeconomic Factors

BACKGROUND:There is a central sensitization mechanism for lumbar disc herniation-specific pain sensitization,and it is unclear whether cyclic RNAs in the paraventricular nucleus brain region are involved in lumbar disc herniation-specific pain sensitization.OBJECTIVE:To investigate the mechanism by which cyclic RNA circ05188 in the paraventricular nucleus of rats with lumbar disc herniation regulates the participation of microRNAs in pain sensitization.METHODS:Fifty-two Sprague-Dawley rats were randomly divided into a sham operation group,a lumbar disc herniation group,a knockdown control group and a circ05188 knockdown group,with 13 rats in each group.Except for the sham operation group,the lumbar disc herniation model was established in the other three groups.On the 7th day after modeling,the hypothalamic paraventricular nucleus of the knockdown control group and circ05188 knockdown group were injected with siRNA-NC and siRNA-circ05188,respectively,at 1 day intervals,for a total of three injections.On the 7th day after modeling,high-throughput sequencing technology was used to detect the expression of differential circRNAs in the hypothalamic paraventricular nucleus of rats in the sham operation group and the lumbar disc herniation group,and RT-qPCR was used to detect the expression of circ05188 and miR-199a-5p in the hypothalamic paraventricular nucleus.On the 3rd,7th,14th,21st,and 28th days after modeling,we detected the mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot in the modeled side of rats in the sham operation group and the lumbar disc herniation group.On the 3rd day after siRNA injection,immunofluorescence staining was used to detect the expression of c-Fos in the hypothalamic paraventricular nucleus of rats in the knockdown control group and circ05188 knockdown group;RT-qPCR was used to detect the expression of circ05188 and miR-199a-5p in the hypothalamic paraventricular nucleus of rats in the knockdown control group and circ05188 knockdown group;on the 5th day after siRNA injection,mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot were detected in the knockdown control group and circ05188 knockdown group.Bioinformatics analysis and dual luciferase reporter elucidated the underlying molecular mechanism of circ05188 in pain sensitization after lumbar disc herniation.RESULTS AND CONCLUSION:High-throughput sequencing results showed that circRNAs were differentially expressed in the paraventricular nucleus brain region of rats with lumbar disc herniation.The expression of circ05188 was higher in the lumbar disc herniation group than in the sham operation group(P<0.05),the expression of miR-199a-5p was lower than in the sham operation group(P<0.05),and the mechanical and thermal mechanical paw withdrawal thresholds of the hindfoot were lower than those of the sham operation group at 3,7,14,and 21 days after modeling.RT-qPCR results showed that compared with the knockdown control group,the expression of c-Fos and circ05188 was lower in the circ05188 knockdown group(P<0.05),while the expression of miR-199a-5p was higher(P<0.05).The mechanical and thermal mechanical paw withdrawal thresholds of the rat's hindfoot in the circ05188 knockdown group were higher than those in the knockdown control group at 1,2,and 3 days after injection.Bioinformatics analysis and dual luciferase reporter assay results showed that miR-199a-5p had a binding site with circ05188 and circ05188/miR-199a-5p competitive endogenous RNA axis.To conclude,lumbar disc herniation induces an increase in circ05188 expression in the paraventricular nucleus of the hypothalamus,which produces central sensitization through the inhibition of miR-199a-5p and ultimately triggers neuropathic pain.