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 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.

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 assess the effects of low-dose esketamine on the median effective dose(ED50)of ciprofol for anesthesia induction in painless gastrointestinal endoscopy.Methods Fifty-nine pa-tients underwent elective painless gastrointestinal endoscopy,26 males and 33 females,aged 18-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,were divided into two groups by random number table method:esketamine combined with ciprofol group(group EC,n = 29)and ciprofol group(group C,n = 30).Group EC received intravenous injection of esketamine 0.3 mg/kg and group C received the same amount of normal saline 2 minutes before administration of ciprofol.The initial anesthesia induction dose of ciprofol was 0.4 mg/kg.If a positive reaction occurs during the examination,the next patient will receive an increase dose of propofol 0.04 mg/kg,otherwise will decrease by propofol 0.04 mg/kg.The positive reaction was defined that the patient's BIS can not be decreased to 60 2 minutes after anesthesia induction,or the cough or body movement reaction occur at level 2 or above when entering the mirror.The dosage of ciprofol,recovery time,discharge time,the occurrence of intraoperative and postoperative adverse reactions were recorded.The ED50,95%effective dose(ED95)and 95%confidence interval(CI)of the two groups were calculated by Probit probability regression analysis.Results Compared with group C,the dosage of ciprofol,the incidence of hypotension and frequency of administration of vasoactive drugs during the exami-nation process in group EC were significantly reduced(P＜0.05).The ED50 of ciprofol for anesthesia in-duction in painless gastrointestinal endoscopy in group EC was 0.21 mg/kg(95%CI 0.12-0.25 mg/kg)and the ED95 was 0.32 mg/kg(95%CI 0.26-0.39 mg/kg).The ED50 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group C was 0.37 mg/kg(95%CI 0.32-0.40 mg/kg)and the ED95 was 0.48 mg/kg(95%CI 0.43-0.54 mg/kg).The ED50 and ED95 of ciprofol for anesthesia induction in painless gastrointestinal endoscopy in group EC was significantly lower than that in group C(P＜0.05).There was no significant difference in other frequency of adverse events between the two groups.Conclusion Esketamine 0.3 mg/kg can reduce the ED50 of ciprofol in painless gastrointestinal endoscopy and reduce the dosage of ciprofol during the examination process,which is safe for painless gastrointestinal endoscopy with stable intraoperative circulation.

Objective·To investigate the potential causal relationship between type l diabetes and colorectal cancer by using Mendelian randomization(MR).Methods·Two-sample bidirectional MR was used to investigate the causal relationship between type 1 diabetes and colorectal cancer.All research data were collected from the IEU Open GWAS Project database.The dataset of type l diabetes included 9 266 cases and 15 574 controls,with correlation analysis in 12 783 129 single nucleotide polymorphisms(SNPs);the dataset of colorectal cancer included 5 657 cases and 372 016 controls,with correlation analysis in 29 999 696 SNPs.The instrumental variables SNPs were screened.The results derived from the inverse-variance weighted(IVW)method were used as the main indicator of effect.The results derived from other four methods,namely MR-Egger regression,weighted median,simple mode,and weighted mode,were used as reference.Sensitivity was analyzed with the leave-one-out method.Heterogeneity was analyzed with Cochran's Q test by using both IVW and MR-Egger methods.Pleiotropy was analyzed with MR-pleiotropy function,and Steiger test was used for directional research.The colocation analysis was used to find out whether the causal relationship between type 1 diabetes and colorectal cancer was caused by the same SNP.The genetic correlation between 2 diseases was analyzed by using the linkage disequilibrium score regression(LDSC).All tests were analyzed by using R language software(version 4.3.1).Results·After being screened,a total of 33 instrumental variables(SNPs)were used.The heterogeneity test results showed that there was heterogeneity among the SNPs(IVW and MR-Egger:P＜0.05),so the effect evaluation was based on the results of the random effect model.MR analysis showed that type 1 diabetes had a significant causal effect on colorectal cancer(P＜0.05)by using IVW,MR-Egger,weighted median and weighted mode.Sensitivity analysis showed that the results were stable.Pleiotropy was not detected in pleiotropy test(P＞0.05).Steiger test showed that the effect of type l diabetes on colorectal cancer was not interfered with by the reverse effect.Reverse MR analysis showed no causal effect of colorectal cancer on type l diabetes(P＞0.05).The results of colocalization analysis showed that the probability of H4 hypothesis was 45.7％,and the causal relationship between the 2 diseases was not caused by the same SNP in the gene sequences.LDSC analysis demonstrated that there was no genetic correlation between the two diseases.Conclusion·Type 1 diabetes may promote colorectal cancer,but colorectal cancer has no effect on type 1 diabetes.

Objective:To establish a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of voliconazole (VRC), posaconazole (PCZ), and linazolam (LNZ) in human serum.Methods:This study is a methodological validation by LC-MS/MS. The blood concentration results of VRC, PCZ, and LNZ in our hospital′s anti-infection patients were collected. Voriconazole, Posaconazole, and Linezolid were accurately weighed and prepared. Linezolid-[2H3] was used as the internal standard. After gradient elution on the ACE PFP column, the residuals were analyzed by LC-MS/MS in the positive electrospray ionization mode and multiple reaction monitor (MRM) mode. The method′s linearity, precision, lower limit of detection, and recovery rate were validated according to standard guidelines.Results:The linear correlation coefficient ( r) of the standard curve was above 0.99 ( r>0.99). The linear range of VRC and PCZ were 0.10 mg/L~10.00 mg/L, and the lower limit of detection were 0.01 mg/L. The linear range of LNZ was 0.50 mg/L~50.00 mg/L, and the lower limit of detection was 0.05 mg/L. The recoveries of VRC, PCZ and LNZ were 90.96%-103.18%, 91.84%-99.17%, and 97.04%-100.41%, respectively. Intra-and inter-batch precision (% CV) for VRC were less than 8.30%. Intra-and inter-batch precision (% CV) for PCZ was less than 9.78%. Intra-and inter-batch precision (% CV) for LNZ was less than 7.14%. Drug concentrations in 155 cases of VRC, 44 cases of PCZ, and 59 cases of LNZ were detected. Conclusion:We have established an LC-MS/MS method for the rapid, accurate, highly specific determination of VRC, PCZ, and LNZ concentrations in human serum. This method is suitable for analyzing large clinical sample sets.

Objective:To investigate the efficacy of Qingruxiao granules combined with tamoxifen in the treatment of breast hyperplasia and its effect on serum hypoxia-inducible factor-alpha (HIF-α), angiopoietin-2 (Ang-2) and prolactin (PRL) levels. Methods:Ninety-eight patients with breast hyperplasia admitted to Xi'an No.3 Hospital from June 2020 to January 2022 were retrospectively included in this study. They were divided into control and observation groups ( n = 49/group) according to different treatments. The control group was treated with tamoxifen alone. The observation group was treated with Qingruxiao granules combined with tamoxifen. Clinical efficacy, symptom score, ultrasound parameters (glandular layer thickness, longest diameter of mass, maximum diameter of hypoechoic area, inner diameter of lactating tube), endocrine hormone levels (estradiol, progesterone, and prolactin), HIF-α, and Ang-2 pre- and post-treatment, as well as the incidence of adverse reactions were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group [93.88% (4/49) vs. 77.55%, χ2 = 5.33, P < 0.05). After treatment, breast mass score, breast pain, systemic accompanying symptom, and nipple discharge in the observation group were (1.34 ± 0.29) points, (1.02 ± 0.36) points, (0.68 ± 0.17) points, (0.97 ± 0.15) points, respectively, which were significantly lower than (1.57 ± 0.23) points, (1.45 ± 0.41) points, (0.95 ± 0.26) points, and (1.28 ± 0.26) points, respectively, in the control group ( t = 4.35, 5.52, 6.08, 7.23, all P < 0.001). The glandular layer thickness, the longest diameter of mass, the maximum diameter of hypoechoic area, and the inner diameter of lactating duct in the observation group were (9.45 ± 1.67) mm, (11.46 ± 3.68) mm, (14.37 ± 4.22) mm, and (1.23 ± 0.39) mm, respectively, which were significantly lower than (11.26 ± 2.51) mm, (16.33 ± 4.01) mm, (19.87 ± 5.01) mm, (1.54 ± 0.48) mm in the control group ( t = 4.20, 2.26, 5.88, 3.51, all P < 0.001). Serum estradiol and prolactin levels in the observation group were (122.35 ± 29.76) ng/L and (205.64 ± 36.42) IU/L, respectively, which were significantly lower than (139.76 ± 30.48) ng/L and (251.49 ± 41.87) IU/L in the control group ( t = 2.86, 5.78, both P < 0.05). Serum progesterone level in the observation group was (9.22 ± 1.57) μg/L, which was significantly higher than (7.18 ± 1.21) μg/L in the control group ( t = -7.20, P < 0.05). Serum HIF-α and Ang-2 levels in the observation group were (0.15 ± 0.05) ng/L and (0.98 ± 0.11) ng/L, respectively, which were significantly lower than (0.24 ± 0.07) ng/L and (1.49 ± 0.22) ng/L in the control group ( t = 7.32, 14.51, both P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Qingruxiao granules combined with tamoxifen can effectively improve clinical symptoms, reduce tumor size, regulate endocrine hormone levels, decrease the expression of angiogenic factors in patients with breast hyperplasia, and is highly safe.

Objective:To evaluate the structural features, stability and postoperative effect of integrated framework, 1+ 1 framework, 2+ 1 framework, 4+ 1 framework, and Y-shaped nasal framework.Methods:A retrospective analysis was performed based on the clinical data of patients underwent in Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital, Central South University from February 2019 to November 2020. According to rhinoplasty framework, the patients were divided into integrated framework group, 1+ 1 framework group, 2+ 1 framework group, 4+ 1 framework group, and Y-shaped framework group. Based on the principle of plane photography, the stability of the nasal framework was evaluated by measuring the nasal tip projection and the nasolabial angle 1 month after surgery, and 12 months after surgery. The satisfaction of patients and the incidence of postoperative complications were collected. The difference in nasolabial angle and nasal tip projection data of postoperation 1 month and postoperative 12 months among each group were analyzed by one-way analysis vaniance or Kruskal-Waliis H test.Bonferroni test or Nemenyi test was used for pairwise comparison between groups. P< 0.05 was considered statistically significant. Results:A total of 201 patients (18 males and 183 females, aged 18-46 years, average aged 26.6±5.9 years)were included in this study and followed up for 12-21 months. There were 45 patients in the integrated framework group, 45 patients in the 1+ 1 framework group, 34 patients in the 2+ 1 framework group, 35 patients in the 4+ 1 framework group, and 42 patients in the Y-shaped framework group. Four patients with Y-shaped framework had significant nasal tip supination 12 months after surgery. Among the patients with 1+ 1 framework, 1 patient showed slight columella distortion 6 months after surgery, and 3 patients showed significant nasal tip subrotation 12 months after surgery. One patient in 2+ 1 framework group developed nasal infection 92 days after surgery. No complications were found in other groups during follow-up. In terms of nasal tip projection during postoperative follow-up, the median difference of nasal tip projection between 12 months and 1 month after surgery in 2+ 1 framework group, integrated framework group, 1+ 1 framework group, and 4+ 1 framework group, and Y-shaped framework group was -0.08 cm, -0.09 cm, -0.20 cm, -0.10 cm and -0.17 cm, respectively. The difference of nasal tip projection among the five groups was statistically significant ( P<0.01). The difference between 2+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant( P<0.05). The difference between 4+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). The difference between integrated nasal framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). The difference between Y-shaped framework group and 1+ 1 framework group was statistically significant ( P<0.05). In terms of nasolabial angle during postoperative follow-up, the median difference of nasolabial angle between 12 months and 1 month after surgery in 2+ 1 framework group, integrated framework group, 1+ 1 framework group, and 4+ 1 framework group, and Y-shaped framework group was -4.20°, -3.80°, -6.50°, -4.10° and -6.35°, respectively. The difference of nasolabial angle among the five groups was statistically significant ( P<0.01). The difference between 2+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant( P<0.05). The difference between 4+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). The difference between integrated nasal framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). Patient satisfaction evaluation, 2+ 1 framework group had the highest satisfaction(34/34, 100.00%), followed by 4+ 1 framework group (34/35, 97.14%), integrated framework group(42/45, 93.33%), Y-shaped framework group(36/42, 85.71%), 1+ 1 framework group(37/45, 82.22%). Conclusion:The changes of nasolabial angle and nasal tip projection in 2+ 1 framework, integrated framework, and 4+ 1 framework were smaller than those in Y-shaped framework and 1+ 1 framework.2+ 1 framework was convenient and had good postoperative stability and high patient satisfaction.

Objective:To evaluate the structural features, stability and postoperative effect of integrated framework, 1+ 1 framework, 2+ 1 framework, 4+ 1 framework, and Y-shaped nasal framework.Methods:A retrospective analysis was performed based on the clinical data of patients underwent in Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital, Central South University from February 2019 to November 2020. According to rhinoplasty framework, the patients were divided into integrated framework group, 1+ 1 framework group, 2+ 1 framework group, 4+ 1 framework group, and Y-shaped framework group. Based on the principle of plane photography, the stability of the nasal framework was evaluated by measuring the nasal tip projection and the nasolabial angle 1 month after surgery, and 12 months after surgery. The satisfaction of patients and the incidence of postoperative complications were collected. The difference in nasolabial angle and nasal tip projection data of postoperation 1 month and postoperative 12 months among each group were analyzed by one-way analysis vaniance or Kruskal-Waliis H test.Bonferroni test or Nemenyi test was used for pairwise comparison between groups. P< 0.05 was considered statistically significant. Results:A total of 201 patients (18 males and 183 females, aged 18-46 years, average aged 26.6±5.9 years)were included in this study and followed up for 12-21 months. There were 45 patients in the integrated framework group, 45 patients in the 1+ 1 framework group, 34 patients in the 2+ 1 framework group, 35 patients in the 4+ 1 framework group, and 42 patients in the Y-shaped framework group. Four patients with Y-shaped framework had significant nasal tip supination 12 months after surgery. Among the patients with 1+ 1 framework, 1 patient showed slight columella distortion 6 months after surgery, and 3 patients showed significant nasal tip subrotation 12 months after surgery. One patient in 2+ 1 framework group developed nasal infection 92 days after surgery. No complications were found in other groups during follow-up. In terms of nasal tip projection during postoperative follow-up, the median difference of nasal tip projection between 12 months and 1 month after surgery in 2+ 1 framework group, integrated framework group, 1+ 1 framework group, and 4+ 1 framework group, and Y-shaped framework group was -0.08 cm, -0.09 cm, -0.20 cm, -0.10 cm and -0.17 cm, respectively. The difference of nasal tip projection among the five groups was statistically significant ( P<0.01). The difference between 2+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant( P<0.05). The difference between 4+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). The difference between integrated nasal framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). The difference between Y-shaped framework group and 1+ 1 framework group was statistically significant ( P<0.05). In terms of nasolabial angle during postoperative follow-up, the median difference of nasolabial angle between 12 months and 1 month after surgery in 2+ 1 framework group, integrated framework group, 1+ 1 framework group, and 4+ 1 framework group, and Y-shaped framework group was -4.20°, -3.80°, -6.50°, -4.10° and -6.35°, respectively. The difference of nasolabial angle among the five groups was statistically significant ( P<0.01). The difference between 2+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant( P<0.05). The difference between 4+ 1 framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). The difference between integrated nasal framework group and 1+ 1 framework group or Y-shaped framework group was statistically significant ( P<0.05). Patient satisfaction evaluation, 2+ 1 framework group had the highest satisfaction(34/34, 100.00%), followed by 4+ 1 framework group (34/35, 97.14%), integrated framework group(42/45, 93.33%), Y-shaped framework group(36/42, 85.71%), 1+ 1 framework group(37/45, 82.22%). Conclusion:The changes of nasolabial angle and nasal tip projection in 2+ 1 framework, integrated framework, and 4+ 1 framework were smaller than those in Y-shaped framework and 1+ 1 framework.2+ 1 framework was convenient and had good postoperative stability and high patient satisfaction.

【Objective】 To investigate the association of normal weight obesity （NWO） with carotid atherosclerosis （CAS） and peripheral arterial stiffness （PAS） in persons received physical examination. 【Methods】 A total of 1 894 people with normal BMI （18.5-23.9 kg/m²） were consecutively enrolled for this study. All these people had completed body fat measurement， carotid artery ultrasound examination and peripheral arterial stiffness detection. Then they were divided into control group， CAS group， PAS group， and CAS + PAS group according to the test results mentioned above. Clinical data were compared between different groups to assess the baseline situation. Besides， Multivariate Logistic regression analysis was performed to determine independent risk factors for atherosclerosis. 【Results】 The proportion of NWO in CAS group， PAS group， and CAS + PAS group was significantly higher than that in normal group （P<0.05）. Univariate analysis results showed that NWO was correlated with greater risks of both CAS and PAS （P<0.05）. However， multiple factors analysis suggested that NWO was not associated with PAS， but with CAS （OR=1.286， 95% CI： 1.032-1.603， P<0.05）. 【Conclusion】 NWO is closely related to the occurrence of CAS and may be an independent risk factor for CAS. Attention should be paid to the body fat mass of the NWO population. Early intervention is needed to prevent the occurrence of CAS in these people.