Objective To explore the inhibitory effect of Xinhui tangerine peel polysaccharides on the mouse skin fibroblasts so as to understand the underlying molecular mechanism.Methods We separated and purified the components of tangerine peel polysaccharides from Xinhui tangerine peel.C57BL/6 mouse skin fibroblasts were isolated and cultured for the cellular experimental study.We set up a blank control group(normal culture)and low-,medium-and high-dose experimental groups(50,100 and 200 μg/mL tangerine peel polysaccharides).After 24 hours of treatment,cell survival rate was assessed by CCK-8 assay.The mRNA and protein expression levels of collagen type Ⅰ(Col1a1),collagen type Ⅲ(Col1a3),TGF-β1 and ACTA2 in fibroblasts were examined by RT-qPCR and Western blotting.Smad3 was examined by Western blotting.Results The cell survival rate in the blank control group,the medium-and high-dose experimental groups was 100％,(90.54±6.74)％,and(78.90±4.24)％,respectively.The relative expression level of Col1a1 protein was 1.13±0.15,0.57±0.16,and 0.48±0.05,respectively;the relative expression level of Col3a1 protein was 0.81±0.13,0.49±0.11 and 0.50±0.03;the relative expression level of TGF-β1 protein was 1.11±0.15,0.60±0.13,and 0.33±0.11;the relative expression level of p-Smad3/Smad3 proteins was 0.96±0.05,0.75±0.06 and 0.71±0.03.The mRNA expression level of Col1a1 was 1.01±0.17,0.58±0.11,and 0.52±0.12;the mRNA expression level of Col3a1 was 1.01±0.12,0.56±0.19,and 0.65±0.14;the expression level of ACTA2 mRNA was 1.01±0.13,0.24±0.04,and 0.22±0.07;the mRNA expression level of TGF-β1 was 1.00±0.09,0.50±0.10,and 0.49±0.15.The relative expression levels of p-Smad3/Smad3 proteins were 0.86±0.06,0.66±0.06,0.55±0.13,0.43±0.09,0.35±0.06,and 0.27±0.12,respectively,after time-related treatment with high-dose tangerine peel polysaccharides.The above indicators in medium-and high-dose tangerine peel polysaccharide groups showed statistically significant differences compared to those in the blank control group(P＜0.05).Conclusion Tangerine peel polysaccharides can inhibit the cell proliferation and the synthesis of keloid-related genes on fibroblasts by inhibiting TGF-β1/Smad3 signaling pathway.

This artical starts from the perspective of"earth stagnation and wood depression"to analyze the dynamic mutual impairment process between breast cancer and mixed anxiety and depressive disorder(MADD),integrating pathological evidence of mutual causality between physical impairment and internal injury by emotional distress,to provide a theoretical framework elucidating the intrinsic unity of the microbiota-neuro-tumor interaction network in the comorbidity vicious cycle.The comorbidity of breast cancer and MADD manifests dynamic mutually aggravating impairment,with core pathogenesis according to the traditional Chinese medicine theory of"earth stagnation and wood depression":spleen earth stagnation leads to dampness-turbidity obstruction,while dysfunction of the middle jiao pivot result in abnormal liver qi conveyance and dispersion;liver depression transforming into fire further over-restricts on spleen earth.Mutual over-restriction and counter-restriction between the two causes toxic fire,phlegm and blood stasis to conglomerate into masses.The lingering disease progression causes mutual damage between body and spirit,leading to progressive consumption until physical collapse and spiritual decline,ultimately culminating in earth exhaustion and wood withering,toxins infiltrating the extraordinary vessels,and divorce of yin-yang.Gut microbiota dysbiosis induces abnormalities in the metabolic-immune-neuroendocrine network,driving emotional disorders and interacting with the tumor microenvironment to exacerbate deterioration.This mechanism not only validates the concept of"earth stagnation and wood depression-mutual physical-mental impairment",but also elucidates its role in inducing multi-system cascade failure,ultimately culminating in a pathological process marked by the emergence of severe clinical manifestations.

This artical starts from the perspective of"earth stagnation and wood depression"to analyze the dynamic mutual impairment process between breast cancer and mixed anxiety and depressive disorder(MADD),integrating pathological evidence of mutual causality between physical impairment and internal injury by emotional distress,to provide a theoretical framework elucidating the intrinsic unity of the microbiota-neuro-tumor interaction network in the comorbidity vicious cycle.The comorbidity of breast cancer and MADD manifests dynamic mutually aggravating impairment,with core pathogenesis according to the traditional Chinese medicine theory of"earth stagnation and wood depression":spleen earth stagnation leads to dampness-turbidity obstruction,while dysfunction of the middle jiao pivot result in abnormal liver qi conveyance and dispersion;liver depression transforming into fire further over-restricts on spleen earth.Mutual over-restriction and counter-restriction between the two causes toxic fire,phlegm and blood stasis to conglomerate into masses.The lingering disease progression causes mutual damage between body and spirit,leading to progressive consumption until physical collapse and spiritual decline,ultimately culminating in earth exhaustion and wood withering,toxins infiltrating the extraordinary vessels,and divorce of yin-yang.Gut microbiota dysbiosis induces abnormalities in the metabolic-immune-neuroendocrine network,driving emotional disorders and interacting with the tumor microenvironment to exacerbate deterioration.This mechanism not only validates the concept of"earth stagnation and wood depression-mutual physical-mental impairment",but also elucidates its role in inducing multi-system cascade failure,ultimately culminating in a pathological process marked by the emergence of severe clinical manifestations.

Objective To explore the inhibitory effect of Xinhui tangerine peel polysaccharides on the mouse skin fibroblasts so as to understand the underlying molecular mechanism.Methods We separated and purified the components of tangerine peel polysaccharides from Xinhui tangerine peel.C57BL/6 mouse skin fibroblasts were isolated and cultured for the cellular experimental study.We set up a blank control group(normal culture)and low-,medium-and high-dose experimental groups(50,100 and 200 μg/mL tangerine peel polysaccharides).After 24 hours of treatment,cell survival rate was assessed by CCK-8 assay.The mRNA and protein expression levels of collagen type Ⅰ(Col1a1),collagen type Ⅲ(Col1a3),TGF-β1 and ACTA2 in fibroblasts were examined by RT-qPCR and Western blotting.Smad3 was examined by Western blotting.Results The cell survival rate in the blank control group,the medium-and high-dose experimental groups was 100％,(90.54±6.74)％,and(78.90±4.24)％,respectively.The relative expression level of Col1a1 protein was 1.13±0.15,0.57±0.16,and 0.48±0.05,respectively;the relative expression level of Col3a1 protein was 0.81±0.13,0.49±0.11 and 0.50±0.03;the relative expression level of TGF-β1 protein was 1.11±0.15,0.60±0.13,and 0.33±0.11;the relative expression level of p-Smad3/Smad3 proteins was 0.96±0.05,0.75±0.06 and 0.71±0.03.The mRNA expression level of Col1a1 was 1.01±0.17,0.58±0.11,and 0.52±0.12;the mRNA expression level of Col3a1 was 1.01±0.12,0.56±0.19,and 0.65±0.14;the expression level of ACTA2 mRNA was 1.01±0.13,0.24±0.04,and 0.22±0.07;the mRNA expression level of TGF-β1 was 1.00±0.09,0.50±0.10,and 0.49±0.15.The relative expression levels of p-Smad3/Smad3 proteins were 0.86±0.06,0.66±0.06,0.55±0.13,0.43±0.09,0.35±0.06,and 0.27±0.12,respectively,after time-related treatment with high-dose tangerine peel polysaccharides.The above indicators in medium-and high-dose tangerine peel polysaccharide groups showed statistically significant differences compared to those in the blank control group(P＜0.05).Conclusion Tangerine peel polysaccharides can inhibit the cell proliferation and the synthesis of keloid-related genes on fibroblasts by inhibiting TGF-β1/Smad3 signaling pathway.

Objective To understand the changing distribution and antimicrobial resistance profiles of Klebsiella strains in 52 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Antimicrobial susceptibility testing was carried out according to the unified CHINET protocol.The susceptibility results were interpreted according to the breakpoints in the Clinical & Laboratory Standards Institute(CLSI)M100 document.Results A total of 241,549 nonduplicate Klebsiella strains were isolated from 2015 to 2021,including Klebsiella pneumoniae(88.0％),Klebsiella aerogenes(5.8％),Klebsiella oxytoca(5.7％),and other Klebsiella species(0.6％).Klebsiella strains were mainly isolated from respiratory tract(48.49±5.32)％.Internal medicine(22.79±3.28)％,surgery(17.98±3.10)％,and ICU(14.03±1.39)％were the top 3 departments where Klebsiella strains were most frequently isolated.K.pneumoniae isolates showed higher resistance rate to most antimicrobial agents compared to other Klebsiella species.Klebsiella isolates maintained low resistance rates to tigecycline and polymyxin B.ESBLs-producing K.pneumoniae and K.oxytoca strains showed higher resistance rates to all the antimicrobial agents tested compared to the corresponding ESBLs-nonproducing strains.The K.pneumoniae and carbapenem-resistant K.pneumoniae(CRKP)strains isolated from ICU patients demonstrated higher resistance rates to majority of the antimicrobial agents tested than the strains isolated from non-ICU patients.The CRKP strains isolated from adult patients had higher resistance rates to most of the antimicrobial agents tested than the corresponding CRKP strains isolated from paediatric patients.Conclusions The prevalence of carbapenem-resistant strains in Klebsiella isolates increased greatly from 2015 to 2021.However,the Klebsiella isolates remained highly susceptible to tigecycline and polymyxin B.Antimicrobial resistance surveillance should still be strengthened for Klebsiella strains.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

OBJECTIVE: To evaluate the effect of general anesthesia on postoperative melatonin secretion in 4-to 6-year-old children with snoring. METHODS: Twenty children with snoring aged 4-6 years of either gender (ASA grade Ⅰ and Ⅱ) were selected for adenoidectomy.Before, during and 3 days after the operation, salivary melatonin levels of the children were measured at 11 selected time points (T1-T11).The illumination intensity and body temperature of the children were recorded at each time point of measurement.The sleep time of the children in 3 days after the operation was recorded, and postoperative pain scores (FLACC) and Riker and Rehabilitation Quality Rating Scale-15(QoR-15) scores were assessed.Sleep Apnea Life Quality Evaluation Questionnaire (OSA-18) was used to evaluate postoperative recovery of the children at 28 days after the operation.The incidence of major adverse events of the children during hospitalization was recorded. RESULTS: No significant difference was found in baseline salivary melatonin level among the 20 children before the operation.Salivary melatonin level at 7 am after the operation (T8) was significantly lowered as compared with that before the surgery (T4)( CONCLUSIONS In preschool children with snoring, general anesthesia affects but does not inhibit melatonin secretion on the first night after surgery, and minor surgeries under general anesthesia in the morning do not cause significant changes in melatonin secretion to cause disturbance of the circadian rhythm in these children.
Anesthesia, General/adverse effects* ; Bodily Secretions ; Child ; Child, Preschool ; Circadian Rhythm ; Humans ; Melatonin ; Snoring

Objective:To determine the dose-effect relationship of nalbuphine preventing injection pain of medium plus long chain triglyceride propofol in pediatric patients undergoing gastroenteroscopy.Methods:Pediatric patients, aged 3-8 yr, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, scheduled for elective gastroenteroscopy, were enrolled in the study.The doses of nalbuphine were determined by up-down sequential allocation, nalbuphine 0.2 mg/kg was injected intravenously in the first child, and 5 min later medium plus long chain triglyceride propofol 2.5 mg/kg was given intravenously.Ambesh 4-point method was used to evaluate the injection pain of propofol.When the prevention of injection pain was ineffective, the dose of nalbuphine was increased in the next patient, otherwise the dose was reduced, and the difference between the two successive doses was 0.01 mg/kg.This process was repeated until the 7th turning point occurred.The ED 50 and ED 95 of nalbuphine and 95% confidence interval (CI) preventing injection pain of propofol were calculated by Probit regression. Results:The ED 50 and ED 95 (95% CI) of nalbuphine preventing medium plus long chain triglyceride propofol injection pain were 1.57 (1.50-1.62) and 1.71 (1.64-2.05) mg/kg, respectively. Conclusion:The ED 50 and ED 95 of nalbuphine preventing injection pain of medium plus long chain triglyceride propofol are 1.57 and 1.71 mg/kg, respectively, in pediatric patients undergoing gastroenteroscopy.

The recent discovery of activator compounds binding to an allosteric site on the NAD