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Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

AIM:To observe the role of enoyl-coenzyme A hydratase/L-3-hydroxyacyl-coenzyme A dehydroge-nase(Ehhadh)in renal tubulointerstitial inflammation in high-fat diet(HFD)fed mice,and to explore its molecular mecha-nism.METHODS:Twenty-four C57BL/6N mice were randomly divided into 4 groups:standard diet(SD)group,HFD group,HFD with Ehhadh overexpression(HFD+Ehh)group and HFD with blank vector(HFD+Vec)group.Each group consisted of 6 mice.The HFD mice were fed with a diet containing 60%fat,20%protein,and 20%carbohydrates for 16 weeks.Briefly,at the end of 8 weeks,the mice in HFD+Ehh or HFD+Vec group were injected with adeno-associated virus 9(AAV9)-Ehhadh or AAV9-vector via the tail vein,and then continued another 8-week HFD feeding.At the end of the experiments,the renal function and morphological changes were observed.The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1 p10,interleukin-1β(IL-1β)and IL-18 in the kidney were detected by Western blot and immunohistochemistry.Immunofluorescence staining was used to detect the colocalization of Ehhadh and peroxisomal biogenesis factor 14(Pex14).ELISA was used to detect the content of IL-1β and IL-18 in the urine.Lipid droplet formation in renal tissues was detected by Nile red staining.Absolute quantitative lip-idomic analysis were used to detect the differential lipid species in renal cortices of the mice in SD,HFD and HFD+Ehh groups.RESULTS:Compared with SD group,the expression of Ehhadh protein was significantly decreased in the peroxi-some of renal tubular epithelium cells in HFD-fed mice(P<0.01).Overexpression of Ehhadh significantly improved renal function(P<0.01)and alleviated the morphological changes of renal tubular epithelial cells in HFD group.Moreover,it significantly inhibited the expression of inflammatory cytokines IL-1β and IL-18 and macrophage infiltration in renal tu-bule interstitium of HFD-fed mice(P<0.01).At the same time,Ehhadh overexpression inhibited HFD-induced NLRP3 inflammasome activation(P<0.01).It also attenuated lipid deposition in renal tubular epithelium cells(P<0.01)and promoted the β-oxidation of long-chain fatty acid such as cholesterol and phospholipids in peroxisomes.CONCLUSION:The Ehhadh inhibits tubulointerstitial inflammation by promoting long-chain fatty acid β-oxidation in peroxisomes and in-hibiting the activation of NLRP3 inflammasome in HFD-fed mice.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

ObjectiveTo examine the protective mechanism of wogonin in SH-SY5Y cells cultured in the conditioned media with lipopolysaccharide （LPS）-induced BV-2 microglia. MethodBV-2 microglia were divided into the blank group， LPS group， low concentration group of wogonin （4 μmol∙L^-1）， medium concentration group of wogonin （8 μmol∙L^-1）， and high concentration group of wogonin （16 μmol∙L^-1）. The LPS group was given 1 mg·L^-1 LPS， and the other three groups were treated with the corresponding concentration of wogonin for 4 h and then given 1 mg·L^-1 LPS. The conditioned media from these groups were used to cultivate SH-SY5Y cells. Cell counting kit-8 （CCK-8） was used to assess the vitality of BV-2 cells in the above groups. The contents of interleukin-6 （IL-6） and tumor necrosis factor-alpha （TNF-α） in the supernatant of BV-2 cells were determined by enzyme-linked immunosorbent assay （ELISA）. The expression of tyrosine hydroxylase （TH） and α-Synuclein （α-Syn） in SH-SY5Y cells was detected by immunohistochemical staining （IHC）. The nuclear transfer and fluorescence expression intensity of nuclear transcription factor-κB p65 （NF-κB p65） protein in SH-SY5Y cells were detected by immunofluorescence staining （IF）. Western blot was used to detect the expression of Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/NF-κB pathway-related proteins in SH-SY5Y cells. ResultThe levels of IL-6 and TNF-α in the supernatant of BV-2 cells in the LPS group were significantly higher than those in the blank group （P<0.01）. Compared with those in the LPS group， the IL-6 content of BV-2 cells in the low concentration group of wogonin was statistically significantly lower （P<0.05）， whereas the IL-6 and TNF-α contents of the medium and high concentration groups of wogonin were statistically lower （P<0.05，P<0.01）. The IL-6 and TNF-α contents in the high concentration group of wogonin decreased most significantly （P<0.01）， and the intervention effect was the best. Compared with that in the blank group， the expression of α-Syn protein in SH-SY5Y cells cultured with conditioned media in the LPS group was significantly increased， and the expression of TH protein was significantly decreased （P<0.05）. Compared with that in the LPS group， α-Syn protein expression in the medium and high concentration groups of wogonin showed a decreasing trend （P<0.05， P<0.01）. TH protein expression was increased in the low， medium， and high concentration groups of wogonin （P<0.05， P<0.01）. Compared with the blank group， NF-κB p65 protein gradually accumulated into the nucleus， and the fluorescence expression intensity was significantly enhanced （P<0.01）. Compared with the LPS group， the NF-κB p65 protein was gradually dispersed outside the nucleus， and the fluorescence expression intensity was gradually weakened in all concentration groups of wogonin. The fluorescence intensity in the high concentration group of wogonin was significantly reduced （P<0.01）. Compared with those in the blank group， the expression levels of TLR4 protein， phosphorylated（p）-NF-κB p65 protein， and MyD88 protein in the LPS group were significantly increased （P<0.05， P<0.01）. Compared with those in the LPS group， the expressions of TLR4 protein， p-NF-κB p65 protein， and MyD88 protein in the medium concentration group of wogonin were all significantly decreased （P<0.05， P<0.01）. The expressions of TLR4 protein， and MyD88 protein in the high concentration group of wogonin were significantly decreased （P<0.05， P<0.01）. ConclusionWogonin may regulate the TLR4/MyD88/NF-κB signaling pathway to inhibit the release of LPS-induced inflammatory factors in BV-2 microglia and protect SH-SY5Y cells， thereby reducing inflammation and achieving neuroprotective effects.

Background The substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. Objective To calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. Methods Using a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. Results Overall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). Conclusion Heat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.

Diabetes is a common chronic non-infectious disease. Diabetic patients not only suffer from metabolic disorders, but are also prone to immune deficiencies and are at a higher risk of being infected with human papillomavirus (HPV). Many studies at home and abroad have shown that the HPV infection rate of patients with diabetes is higher than that of non-diabetic patients. Patients with diabetes can benefit from HPV vaccination, and the tolerance is good. HPV vaccination is recommended for diabetic patients. This article reviews the research on diabetes, HPV infection, and HPV vaccine, which will provide references for HPV vaccination in diabetic patients.