Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

OBJECTIVE To investigate the impact of perilla alcohol on pulmonary vascular remod-eling in hypoxia-induced pulmonary hypertension(HPH)rats and to assess its regulatory effects on the angiotensin-converting enzyme 2(ACE2)-angiotensin(1-7)[Ang(1-7)]-mas proto-oncogene receptor(Mas)and ACE-angiotensinⅡ(AngⅡ)-angiotensin type 1 receptor(AT1R)axes.METHODS An HPH rat model was established by keeping them in a hypobaric chamber that simulated an altitude of 5 000 m for 28 d.Male SD rats were randomly divided into the control group,hypoxia group,hypoxia+sildenafil group(ig administration of 30 mg·kg-1),and hypoxia+perillyl alcohol groups(ig administration of 25,50 and 100 mg·kg-1 respectively).After 28 d,the levels of glutamic-oxaloacetic transaminase(GOT),glutamic-pyruvic transaminase(GPT),and blood urea nitrogen(BUN)in rat serum were measured to evaluate the toxic effects of perillyl alcohol on rat organs.Mean pulmonary artery pressure(mPAP)was measured via right ventricular catheterization.HE staining was used to observe the patho morphological changes of pulmonary vessels in HPH rats and measure the percentages of the vascularwall area[WA(%)],wall thickness[WT(%)],lumen area[LA(%)].The right ventricular hypertrophy level and α-smooth muscle actin(α-SMA)expression level were detected by immunohistochemistry and immunofluorescence.Western blotting was used to detect the protein expression levels of α-SMA,ACE,AT1R,AngⅡ,ACE2 and Mas in lung tissues of rats.Enzyme-linked immunosorbent assay(ELISA)was employed to mea-sure the content of Ang(1-7)in lung tissues.RESULTS Compared with the control group,the serum levels of GOT,GPT and BUN in the hypoxia group rats were significantly increased,but were signifi-cantly decreased by perillyl alcohol and sildenafil intervention.Compared with the control group,mPAP,WA(%),WT(%),right ventricular inner diameter(RVID),right ventricular free wall thickness(RVFWT)and fibrosis levels were significantly increased in the hypoxia group,while LA(%)was signifi-cantly decreased.Besides,the protein expression levels of α-SMA,ACE,AT1R and AngⅡ in lung tissues were significantly elevated while those of ACE2 and Mas,as well as Ang(1-7)content were signifi-cantly decreased in hypoxia group compared to the control group.Following intervention with perillyl alcohol and sildenafil,the protein expression levels of ACE and AngⅡin lung tissues of HPH rats were significantly decreased compared to the model group while those of ACE2 and Mas receptor,along with the content of Ang(1-7),were significantly increased.Perillyl alcohol significantly reduced the protein expression level of AT1R while sildenafil had no significant effect.CONCLUSION Perillyl alcohol can lower mPAP levels by improving pulmonary vascular remodeling and reducing pulmonary vascular fibrosis in HPH rats.The mechanism may be related to the regulatory effects on the ACE-AngⅡ-AT1R and ACE2-Ang(1-7)-Mas axes.

Objective:The Social Isolation Scale for people with type 2 diabetes mellitus (T2DM) was developed and tested for reliability and validity, which provided an effective tool for measuring the social isolation level of patients with T2DM.Methods:The initial scale was developed through literature review, qualitative interviews, and expert consultation. Convenience sampling method was used to select T2DM patients who met the inclusion and exclusion criteria for questionnaire survey. The item analysis method was used to select the items of the scale. Exploratory and confirmatory factor analyses were used to evaluate construct validity. The content validity of the scale was evaluated by the scale-level content validity index and the item-level content validity index. The criterion validity was verified by using the Lubben Social Network Scale-6 and the De Jong Gierveld Loneliness Scale. Reliability was tested through internal consistency and test-retest reliability.Results:Through literature review and qualitative interviews, 30 items of the scale were selected to form the first version scale. After two rounds of inquiries from 16 experts (expert authority coefficient = 0.897), the second version of the scale was formed. A total of 407 questionnaires were distributed in two stages using the second version scale. Among the 407 patients, there were 214 males and 193 females. Exploratory factor analysis extracted 4 common factors, with a cumulative variance contribution rate of 61.338%. The final scale was determined to include 4 dimensions and 16 items, with the dimensions being "social support network", "frequency of social participation", "satisfaction with interpersonal relationships", and "diabetes-related sense of isolation".The average content validity index at the scale level was 0.929, the content validity index at the item level was 0.830 - 1.000, and the criterion validity was - 0.647 and 0.681. The Cronbach′s α coefficient of the total scale was 0.822, and the test-retest reliability was 0.858.Conclusions:The Social Isolation Scale for people with T2DM has good reliability and validity. It is a reliable and valid tool for assessing social isolation in T2DM patients.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

OBJECTIVE To investigate the impact of perilla alcohol on pulmonary vascular remod-eling in hypoxia-induced pulmonary hypertension(HPH)rats and to assess its regulatory effects on the angiotensin-converting enzyme 2(ACE2)-angiotensin(1-7)[Ang(1-7)]-mas proto-oncogene receptor(Mas)and ACE-angiotensinⅡ(AngⅡ)-angiotensin type 1 receptor(AT1R)axes.METHODS An HPH rat model was established by keeping them in a hypobaric chamber that simulated an altitude of 5 000 m for 28 d.Male SD rats were randomly divided into the control group,hypoxia group,hypoxia+sildenafil group(ig administration of 30 mg·kg-1),and hypoxia+perillyl alcohol groups(ig administration of 25,50 and 100 mg·kg-1 respectively).After 28 d,the levels of glutamic-oxaloacetic transaminase(GOT),glutamic-pyruvic transaminase(GPT),and blood urea nitrogen(BUN)in rat serum were measured to evaluate the toxic effects of perillyl alcohol on rat organs.Mean pulmonary artery pressure(mPAP)was measured via right ventricular catheterization.HE staining was used to observe the patho morphological changes of pulmonary vessels in HPH rats and measure the percentages of the vascularwall area[WA(%)],wall thickness[WT(%)],lumen area[LA(%)].The right ventricular hypertrophy level and α-smooth muscle actin(α-SMA)expression level were detected by immunohistochemistry and immunofluorescence.Western blotting was used to detect the protein expression levels of α-SMA,ACE,AT1R,AngⅡ,ACE2 and Mas in lung tissues of rats.Enzyme-linked immunosorbent assay(ELISA)was employed to mea-sure the content of Ang(1-7)in lung tissues.RESULTS Compared with the control group,the serum levels of GOT,GPT and BUN in the hypoxia group rats were significantly increased,but were signifi-cantly decreased by perillyl alcohol and sildenafil intervention.Compared with the control group,mPAP,WA(%),WT(%),right ventricular inner diameter(RVID),right ventricular free wall thickness(RVFWT)and fibrosis levels were significantly increased in the hypoxia group,while LA(%)was signifi-cantly decreased.Besides,the protein expression levels of α-SMA,ACE,AT1R and AngⅡ in lung tissues were significantly elevated while those of ACE2 and Mas,as well as Ang(1-7)content were signifi-cantly decreased in hypoxia group compared to the control group.Following intervention with perillyl alcohol and sildenafil,the protein expression levels of ACE and AngⅡin lung tissues of HPH rats were significantly decreased compared to the model group while those of ACE2 and Mas receptor,along with the content of Ang(1-7),were significantly increased.Perillyl alcohol significantly reduced the protein expression level of AT1R while sildenafil had no significant effect.CONCLUSION Perillyl alcohol can lower mPAP levels by improving pulmonary vascular remodeling and reducing pulmonary vascular fibrosis in HPH rats.The mechanism may be related to the regulatory effects on the ACE-AngⅡ-AT1R and ACE2-Ang(1-7)-Mas axes.

Objective:The Social Isolation Scale for people with type 2 diabetes mellitus (T2DM) was developed and tested for reliability and validity, which provided an effective tool for measuring the social isolation level of patients with T2DM.Methods:The initial scale was developed through literature review, qualitative interviews, and expert consultation. Convenience sampling method was used to select T2DM patients who met the inclusion and exclusion criteria for questionnaire survey. The item analysis method was used to select the items of the scale. Exploratory and confirmatory factor analyses were used to evaluate construct validity. The content validity of the scale was evaluated by the scale-level content validity index and the item-level content validity index. The criterion validity was verified by using the Lubben Social Network Scale-6 and the De Jong Gierveld Loneliness Scale. Reliability was tested through internal consistency and test-retest reliability.Results:Through literature review and qualitative interviews, 30 items of the scale were selected to form the first version scale. After two rounds of inquiries from 16 experts (expert authority coefficient = 0.897), the second version of the scale was formed. A total of 407 questionnaires were distributed in two stages using the second version scale. Among the 407 patients, there were 214 males and 193 females. Exploratory factor analysis extracted 4 common factors, with a cumulative variance contribution rate of 61.338%. The final scale was determined to include 4 dimensions and 16 items, with the dimensions being "social support network", "frequency of social participation", "satisfaction with interpersonal relationships", and "diabetes-related sense of isolation".The average content validity index at the scale level was 0.929, the content validity index at the item level was 0.830 - 1.000, and the criterion validity was - 0.647 and 0.681. The Cronbach′s α coefficient of the total scale was 0.822, and the test-retest reliability was 0.858.Conclusions:The Social Isolation Scale for people with T2DM has good reliability and validity. It is a reliable and valid tool for assessing social isolation in T2DM patients.

Ischemic stroke is an acute cerebro-vascular disease with high disability and mortality,is the most common cause of death in China.De-spite years of research,there are still no biomark-ers for stroke,and the molecular mechanisms re-main largely unknown.In the past decade,single-cell sequencing technology,as a rapidly developing emerging technology,can conduct high-throughput sequencing of multiple omics including genome,transcriptome,epigenome and proteome at the level of a single cell,providing a new way to discov-er biomarkers and analyze pathological mecha-nisms.In this paper,the progress of single-cell multi-omics sequencing technology and its applica-tion in the discovery of biomarkers,pathological mechanisms and drug development of ischemic stroke are introduced in detail,in order to provide valuable reference for precision medicine of isch-emic stroke.

Objective:To investigate the correlation between psychological resilience and the risk of all-cause mortality in disabled older individuals.Methods:A total of 8, 089 disabled older adults were selected from the Chinese Longitudinal Healthy Longevity Survey(1998-2018)after screening with the Katz index.Psychological resilience was assessed at baseline using a seven-item self-rating scale.Participants were followed up until 2018, with survival data being recorded.Restricted cubic spline regression and Cox proportional hazard models were employed to analyze the association between psychological resilience and all-cause mortality, as well as to explore the potential interaction between psychological resilience and levels of disability.Results:After adjusting for potential confounding factors, a linearly negative relationship was found between levels of psychological resilience and mortality risk( P-nonlinear 0.781).Stratified analyses by degree of disability revealed that for older adults with mild disability, a 1 standard deviation increase in psychological resilience was associated with a 12% decrease in mortality risk( HR=0.88, 95% CI: 0.83-0.94).However, no significant association was observed between psychological resilience and mortality risk in severely disabled participants.A significant interaction was noted between resilience levels and degree of disability( P-interaction=0.026). Conclusions:This study offers observational evidence supporting the importance of maintaining psychological resilience in reducing mortality risk among disabled older individuals, particularly those with mild disability.The findings highlight the potential benefits of psychological interventions for older adults with varying levels of functional decline.