ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To investigate the impact of donor human leukocyte antigen (HLA) -Bw4 expression on natural killer (NK) cell reconstitution and transplant outcomes in recipients undergoing haploidentical hematopoietic stem cell transplantation (HSCT) from maternal or related donors without ex vivo T-cell depletion.Methods:This study prospectively enrolled 32 patients who received T-replete haploidentical HSCT from maternal or collateral donors (cohort 1) to evaluate the facilitating effect of donor HLA-Bw4 expression on NK cell reconstitution. Furthermore, a retrospective analysis was conducted on 278 patients who underwent T-replete haploidentical HSCT from maternal or collateral donors (cohort 2) to analyze the impact of donor HLA-Bw4 expression on HSCT outcomes. Thus, a comparison was made between the effects of donor HLA-Bw4 expression on HSCT outcomes in patients receiving or not receiving post-transplant cyclophosphamide (PT-Cy) conditioning.Results:Donors expressing HLA-Bw4 alleles facilitated NK cell reconstitution and functional recovery, which remained unaffected by PT-Cy. Donors with HLA-Bw4 expression were associated with reduced transplant-related mortality (TRM), particularly mortality related to infections. The use of PT-Cy did not impact the ability of donor HLA-Bw4 to decrease TRM.Conclusion:In haploidentical HSCT from maternal or related donors without ex vivo T-cell depletion, the presence of donor HLA-Bw4 expression promotes rapid NK cell reconstitution and functional recovery and is significantly associated with lower TRM, especially infection-related mortality. These findings underscore the clinical significance of donor HLA-Bw4 expression in patients who underwent HSCT. Hence, the consideration of donor HLA-Bw4 in recipient selection and HSCT strategies holds important clinical implications.

Objective:To study the prevalence and association factors of depressive and anxiety disorders in the hypertensive population.Methods:Using the database obtained from the 2013 China Chronic Disease and Risk Factor Surveillance and the 2013-2015 China Mental Health Survey,4 861 hypertensive residents were used as study subjects.And using the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)as diagnostic criterion for depressive and anxiety disorders,the 12-month prevalence was calculated.Multifactorial lo-gistic regression models were used to explore the association factors of hypertension comorbid depressive and anxie-ty disorders.Results:The 12-month prevalence rates of depressive disorders and anxiety disorders were 4.1％and 5.0％in 4 861 hypertensive residents.Chinese Han[OR(95％CI):2.00(1.01-3.93)],lack of sleep[OR(95％CI):1.82(1.34-2.48)],having myocardial infarction[OR(95％CI):2.35(1.18～4.67)]and stroke in the past year[OR(95％CI):2.10(1.19-3.72)],and chronic obstructive pulmonary disease[OR(95％CI):2.11(1.11-4.05)]were risk factors of hypertension comorbid depressive disorder.Hypertensive people with controlled blood pressure[OR(95％CI):2.01(1.30-3.13)]had a higher risk of co-morbid depressive disorder than those with blood pressure above the normal range on this measurement.Chinese Han[OR(95％CI):2.51(1.32-4.80)],Southwest China[OR(95％CI):1.64(1.02-2.63)],and lack of sleep[OR(95％CI):1.45(1.09-1.93)]were risk factors of hypertension comorbid anxiety disorder.Former but current non-smoking[OR(95％CI):0.48(0.23-0.99)]was a protective factor of hypertension comorbid anxiety disorder.Conclusion:The 12-month prevalence of anxiety disorder was higher than that of depressive disorder in this hypertensive population.Both Han and sleep deprived hypertensive people had a higher risk of comorbid depressive and anxiety disorders.

[Objective]To evaluate the clinical outcomes of combining electroacupuncture with rectal function training for treating post-stroke constipation(PSC).[Methods]A total of sixty patients of PSC were enrolled in the study at the Rehabilitation Department of Northern Jiangsu People's Hospital from December 2021 to March 2023.They were randomly assigned using a random number table method to enter the treatment group(29 cases,with 1 case dropped out)or the control group(29 cases,with 1 case dropped out).The control group received comprehensive and individualized rectal function training,and the treatment group received electroacupuncture therapy on the basis of the control group,all of which were treated for 4 weeks.The study involved assessing the Cleveland Clinic Score(CCS),pelvic floor surface electromyography,and therapeutic outcomes before and after treatment.[Results]No statistically significant difference was observed between the two groups prior to treatment(P>0.05).Following 4 weeks of treatment,both groups experienced a significant decrease in CCS scores(P<0.001),with the treatment group displaying a lower CCS score compared with the control group(P<0.01).After treatment,the electromyographic values significantly increased in both groups during the rapid contraction,tension contraction,and endurance contraction stages(P<0.001),and the electromyographic values of the above stages in the treatment group were higher than those in the control group(P<0.05).The total effective rate of the treatment group(93.10%)was higher than that of the control group(72.41%),and the difference was statistically significant(P<0.05).[Conclusion]Electroacupuncture combined with rectal function training in the treatment of PSC can improve the defecation frequency and accompanying symptoms of patients,improve the muscle strength of pelvic floor fast and slow muscles and the endurance of slow muscles,and improve the therapeutic effect.

Background/Aims: Metabolic syndrome is common in patients with acute pancreatitis and its components have been reported to be associated with infectious complications. In this post hoc analysis, we aimed to evaluate whether metabolic abnormalities impact the effect of immuneenhancing thymosin alpha-1 (Tα1) therapy in acute necrotizing pancreatitis (ANP) patients. Methods: All data were obtained from the database for a multicenter randomized clinical trial that evaluated the efficacy of Tα1 in ANP patients. Patients who discontinued the Tα1 treatment prematurely were excluded. The primary outcome was 90-day infected pancreatic necrosis (IPN) after randomization. Three post hoc subgroups were defined based on the presence of hyperglycemia, hypertriglyceridemia, or both at the time of randomization. In each subgroup, the correlation between Tα1 and 90-day IPN was assessed using the Cox proportional-hazards regression model. Multivariable propensity-score methods were used to control potential bias. Results: Overall, 502 participants were included in this post hoc analysis (248 received Tα1 treatment and 254 received matching placebo treatment). Among them, 271 (54.0%) had hyperglycemia, 371 (73.9%) had hypertriglyceridemia and 229 (45.6%) had both. Tα1 therapy was associated with reduced incidence of IPN among patients with hyperglycemia (18.8% vs 29.7%: hazard ratio, 0.80; 95% confidence interval, 0.37 to 0.97; p=0.03), but not in the other subgroups. Additional multivariate regression models using three propensity-score methods yielded similar results. Conclusions Among ANP patients with hyperglycemia, immune-enhancing Tα1 treatment was associated with a reduced risk of IPN (ClinicalTrials.gov, Registry number: NCT02473406).

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10⁺ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10⁺ M2 macrophage production.

[This corrects the article DOI: 10.1016/j.apsb.2022.10.016.].

Objective:To investigate the effects of remimazolam besylate and midazolam on postoperative cognitive function of patients undergoing gynecologic laparoscopic surgery under general anesthesia.Methods:From May 2019 to January 2021, 120 patients with gynecological laparoscopic surgery under general anesthesia in Haikou Maternal and Child Health Hospital were selected and divided into control group (60 cases) and observation group (60 cases) by random number table. The control group was given 0.05 mg/kg midazolam and 0.50 μg/kg sufentanil and 0.15 mg/kg vecuronium bromide were used for anesthesia induction. Patients in the observation group were given 0.3 mg/kg remimazolam besylate and 0.50 μg /kg sufentanil and 0.15 mg/kg vecuronium were used for anesthesia induction. The levels of hemodynamic indexes before anesthesia (T 0), during anesthesia (T 1), and after intubation (T 2) as well as the levels of postoperative anesthesia recovery indexes were compared between the two groups. The Visual Analogue Scale (VAS) score and Mini-Mental State Examination (MMSE) scores were recorded and compared before surgery, 24 h, 72 h after surgery. The total incidence of adverse reactions after surgery was recorded and compared between the two groups. Results:The heart rate (HR) at T 1 and T 2 in the two groups was higher than that at T 0, the oxygen saturation (SpO 2) at T 1 and T 2 was lower than that at T 0, the mean arterial pressure (MAP) at T 1 was lower than that at T 0, and the MAP at T 2 was higher than that at T 0, with statistically significant difference (all P<0.05); The HR and MAP at T 1 and T 2 in the observation group were lower than those in the control group, and SpO 2 was higher than those in the control group (all P<0.05); The recovery time of spontaneous respiration, eye opening time and extubation time in the observation group were significantly shorter than those in the control group (all P<0.05); The MMSE score at 24 h and 72 h after operation was lower than that before operation, and the VAS score at 24 h was higher than that before operation in both groups (all P<0.05); The MMSE scores in the observation group at 24 h and 72 h after operation were significantly higher than those in the control group (all P<0.05), and there was no significant difference in the VAS scores at 24 h and 72 h after operation between the two groups ( P>0.05); There was no significant difference in the total incidence of adverse reactions between the two groups (all P>0.05). Conclusions:Remimazolam besylate has little effect on cognitive function of patients undergoing gynecologic laparoscopic surgery under general anesthesia, with fast recovery and high safety, which is worthy of clinical promotion.

Objective:To analyze the comorbidity status and influencing factors of hypertension, diabetes, and dyslipidemia among middle-aged and elderly Chinese adults and to provide support for the "co-management of three diseases".Methods:Using the relevant information collected from the National Chronic Disease and Risk Factor Surveillance in China in 2018, 134 950 permanent residents aged ≥45 years were selected as the research objects. After being weighed, the prevalence and comorbidity of hypertension, diabetes, and dyslipidemia in residents with different groups were compared; a multivariate logistic regression model was used to explore the influencing factors of comorbidity of the "three diseases".Results:The prevalence of hypertension, diabetes, and dyslipidemia among middle-aged and elderly Chinese adults were 46.0% (95% CI:45.1%-47.0%), 19.5% (95% CI:18.7%-20.2%), 43.3% (95% CI:42.3%-44.4%), respectively. The comorbidity rates of hypertension and diabetes, hypertension and dyslipidemia, and diabetes and dyslipidemia were 12.3% (95% CI:11.7%-12.8%), 22.8% (95% CI:22.1%-23.4%),11.6% (95% CI:11.1%-12.0%), respectively; the comorbidity rate of hypertension, diabetes, and dyslipidemia was 7.6% (95% CI: 7.2%-8.0%). These comorbidity rates increased with age and BMI, which was more significant in the urban areas than rural areas and more outstanding in North and Northeast China ( P<0.05). The comorbidity rate of hypertension, diabetes, and higher cholesterol was 1.9% (95% CI:1.7%-2.1%). The comorbidity rate of hypertension, diabetes, and higher low-density lipoprotein was 1.6% (95% CI:1.4%-1.7%), which was higher in women than in men ( P<0.05). Multivariate logistic regression results showed that male, age, city, overweight/obesity, excessive drinking, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep duration <7 hours were risk factors for the comorbidity of the "three diseases". Conclusions:The comorbidity of hypertension, diabetes, and dyslipidemia, is common among middle-aged and elderly adults in China; comprehensive prevention and control of risk factors and "co-management of three diseases" are critical measures for health promotion in middle-aged and elderly populations.