Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Background: and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT. Methods: Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery. Results: A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24). Conclusion Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.

Objective: To investigate the mental health status and related factors among primary and secondary school students in western Yunnan Province, so ao to provide scientific evidences for advancing mental health education. Methods: In June 2024, a stratified cluster sampling method was employed to select 4 584 students from 18 schools across Diqing Tibetan Autonomous Prefecture, Lincang City and Baoshan City three regions in western Yunnan Province. The Mental Health Test (MHT) was used for assessment. Latent class analysis (LCA) and Logistic regression were applied for data classification and related factor analysis respectively. Results: The overall positive detection rate of MHT was 11.81%, with a mean total score of 40.50±19.25. The predominant issues were learning anxiety (58.4%), hypersensitivity tendency (31.1%), and self blame tendency (23.1%). LCA categorized students into four groups:severe psychological problems group (74.4% detection rate), learning anxiety hypersensitivity group ( 16.4 %), learning anxiety physical symptoms group (9.2%), and healthy group (0). Logistic regression revealed that compared with the healthy group, the severe problems group showed higher risks among females ( OR =3.01), junior/senior high school students ( OR =1.88/4.02), and those with authoritarian parenting ( OR =3.54); the anxiety hypersensitivity group had higher risks for females ( OR =1.87), senior high students ( OR =1.54), boarders ( OR =1.31), and authoritarian parenting recipients ( OR = 1.85 ); the anxiety physical symptoms group demonstrated increased risks among females ( OR =2.22), senior high students ( OR =2.58), and authoritarian parenting recipients ( OR =2.74), while lower risks were observed for students with parent/grandparent guardians ( OR =0.38) and non only children ( OR =0.58) (all P <0.05). Conclusions Mental health problems are prominent among students in western Yunnan, with gender, grade level, boarding status, guardian type, and parenting style being key determinants. Recommendations include strengthening mental health education, prioritizing left behind children s psychological well being and promoting healthy development.

Silent mutations within the RAS  gene have garnered increasing attention for their potential roles in tumorigenesis and therapeutic strategies. Kirsten-RAS ( KRAS ) mutations, predominantly oncogenic, are pivotal drivers in various cancers. While extensive research has elucidated the molecular mechanisms and biological consequences of active KRAS  mutations, the functional significance of silent mutations remains relatively understudied. This review synthesizes current knowledge on KRAS  silent mutations, highlighting their impact on cancer development. Silent mutations, which do not alter protein sequences but can affect RNA stability and translational efficiency, pose intriguing questions regarding their contribution to tumor biology. Understanding these mutations is crucial for comprehensively unraveling KRAS -driven oncogenesis and exploring novel therapeutic avenues. Moreover, investigations into the clinical implications of silent mutations in KRAS -mutant tumors suggest potential diagnostic and therapeutic strategies. Despite being in early stages, research on KRAS  silent mutations holds promise for uncovering novel insights that could inform personalized cancer treatments. In conclusion, this review underscores the evolving landscape of KRAS  silent mutations, advocating for further exploration to bridge fundamental biology with clinical applications in oncology.
Humans ; Mutation/genetics* ; Neoplasms/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Animals

Peptide-based therapies have attracted considerable interest in the treatment of cancer, diabetes, bacterial infections, and neurodegenerative diseases due to their promising therapeutic properties and enhanced safety profiles. This review provides a comprehensive overview of the major trends in peptide drug discovery and development, emphasizing preclinical strategies aimed at improving peptide stability, specificity, and pharmacokinetic properties. It assesses the current applications and challenges of peptide-based drugs in these diseases, illustrating the pharmaceutical areas where peptide-based drugs demonstrate significant potential. Furthermore, this review analyzes the obstacles that must be overcome in the future, aiming to provide valuable insights and references for the continued advancement of peptide-based drugs.
Humans ; Peptides/pharmacology* ; Animals ; Neoplasms/drug therapy* ; Drug Discovery ; Neurodegenerative Diseases/drug therapy* ; Diabetes Mellitus/drug therapy*

Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions,expects to provide research support for the study of traditional Chinese medicine (TCM) treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet,a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment,and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass,food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions,PASI score,the value of transdermal water loss (TEWL),and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index,changes in the histopathological morphology of liver tissue under HE staining,changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR,and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group,the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass (P<0.001),significantly lower food intake (P<0.005),and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur,mental fatigue,etc. appeared. The TWEL were significantly increased(P<0.001),and the PASI scores also significantly increased(P<0.001). HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+neutrophil subpopulation,CD11binLy6Chigh monocyte subpopulation,CD11binCD11chigh classical dendritic cell subpopulation,F4/80-CD11c+dendritic cell subpopulation was significantly increased (P<0.001). HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration,and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased (P<0.005). The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated(P<0.005,P<0.001),while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased (P<0.05,P<0.01). ABCA1 protein level in skin increased(P>0.05). Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern,which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern.

Objective Analyze the temporal trend of ischemic stroke(IS)mortality among the residents of Tengzhou City of Shandong Province during the period of hypertension control from 2013 to 2021.Methods On January 1,2013,Tengzhou City,Shandong Province,began its hypertension control program.The IS mortality rate was calculated using the mortality data from January 1,2013 to December 31,2021,and analyzed for its time trend among residents with different characteristics.The registered population was derived from the Public Security Bureau of Tengzhou City,Shandong Province,and the age and sex standardized mortality rate was calculated using the data of China's 7th population census in 2020.The Chi-square test was used to compare the differences in mortality rate,and Cochran-Armitage trend test was used to compare the time trend and age trend of mortality rate.Results The overall crude and standardized mortality rates of IS in Tengzhou showed a temporal trend from 2013 to 2021(Z values were 12.647,7.305,respectively;all P＜0.001),and decreased by 23.77％and 30.99％(Z values were-7.393,-9.975,respectively;all P＜0.001)respectively in 2021 compared with 2019.The crude mortality rate of IS in male increased by 13.27％in 2019 compared with 2017,while the crude and standardized mortality rate in female decreased by 16.39％and 19.49％in 2018 compared with 2017,respectively,with statistical significance(x2 values were 7.160,9.789,and 15.109,respectively;all P＜0.05).Except the crude mortality rates in 2013 and 2015,the crude mortality rates and standardized mortality rates for males in other years were all higher than those for females,with statistically significant differences(x2 values:25.816-124.040,all P＜0.001).The crude mortality rate for IS increased with age in all years(Z values:42.604-61.025,all P＜0.001).The proportion of IS deaths among those aged≥65 was 85.85％.The overall crude mortality rates of the age group of male 45-54 years old showed a temporal trend from 2013 to 2021(Z=3.035,P＜0.01),while females in the same age group did not show a temporal trend(P＞0.05).The IS mortality rate in urban areas decreased from 62.61 per 100 000 in 2013 to 54.00 per 100 000 in 2021(Z=-2.097,P＜0.05).The rural areas increased by 213.15％in 2019 compared with 2013 and decreased by 22.75％in 2021 compared with 2019(Z values were 19.074,-6.390,respectively;all P＜0.001).Conclusions The IS mortality rate in Tengzhou City showed a decreasing trend in urban areas from 2013 to 2021,and a decreasing trend in rural areas after 2019.Compared to females,there is a trend of younger mortality among males in the age range of 45-54.Males and rural IS patients should be given special attention.

Objective:To analyze the trends of coronary heart disease mortality in Tengzhou city of Shandong province from 2013 to 2021.Methods:The data of coronary heart disease (ICD-10: I20-I25) from January 2013 to December 2021 were obtained from the Chronic Disease Surveillance Information System-Coronary Heart Disease Management Module of Shandong province; the population data were provided by Tengzhou Public Security Bureau. The 95% confidence interval ( CI) of the rate was calculated using the binomial exact method. The age-standardized mortality rate (ASMR) was calculated based on 2020 National Population Census. The trends of mortality rate were analyzed using the Cochran-Armitage trend test. Results:During 2013 to 2021, there were 20 667 coronary heart disease deaths in Tengzhou city, with an average of 2 296 cases per year. The male-to-female ratio was 1.09∶1, and 80.98% (16 736/20 667) of the death cases were aged 65 years or older. The crude mortality rate and ASMR of coronary heart disease were 131.84/10 5 and 168.22/10 5 in 2013, respectively. The crude mortality rate increased by 13.67% from 2013 to 2021 ( P<0.001) with an average annual increase of 1.59%; while the ASMR decreased by 18.65% from 2013 to 2021 ( P<0.05) with an average annual decease of 2.34%. The crude mortality rate of coronary heart disease in men and women showed an upward trend, with the difference in the increase for women being statistically significant ( P<0.01); while the ASMR both in men and women showed a downward trend ( P<0.001). The crude death rates from 2013 to 2021 in age groups of 65 or older for men and women decreased by 22.40% and 19.73%, respectively (both P<0.001); while the crude death rate for age groups of 44 or younger in men showed an upward trend ( P<0.05). The crude death rate among urban residents decreased by 5.22% from 2013 to 2021 with an annual decrease of 0.67% ( P>0.05); while the crude death rate among rural residents increased by 19.29% with an annual increase of 2.18% ( P<0.001). The overall crude death rate among urban residents was higher than that among rural residents (all P<0.05). Conclusions:From 2013 to 2021, the crude mortality rate of coronary heart disease in Tengzhou city of Shandong province shows an increasing trend while the age-standardized mortality rate shows a decreasing trend. The crude mortality rate of coronary heart disease in people aged 65 and above shows a decreasing trend. In addition, the change trends are different between women and men, and between urban and rural areas.

Objective:To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy.Methods:100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ2 test and Fisher's exact test were used to compare categorical variables. Results:HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks ( n = 54) during subsequent treatment compared to those who did not ( n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients ( P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy ( r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion:HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.