AIM To investigate the effects of Jisuishang Formula on neurological function and ferroptosis in a rat model of cervical spondylotic myelopathy(CSM).METHODS The CSM rat models were established and randomly assigned to the model group,the Fer-1 group(2 g/kg Ferrostatin-1 via intraperitoneal injection),the low-dose(9.7 g/kg,intragastrically),medium-dose(19.4 g/kg,intragastrically)and high-dose(38.8 g/kg,intragastrically)Jisuishang Formula groups,and the sham operation group,with 6 rats in each group.Following 4 weeks of treatment administration,BBB locomotor scores and oblique plate test result were recorded to assess their neurological function in rats.Histopathological evaluation utilized HE staining for spinal cord tissue pathology,Nissl staining for Nissl body visualization,and Prussian blue staining for iron ion deposition analysis.Protein expressions of Nrf2,SLC7A11,GPX4,HO-1,TFRC and Cox2 in spinal cord tissues was detected by immunofluorescence and Western blot,while mRNA expressions were quantified using RT-qPCR.RESULTS Compared to the sham group,the CSM model group exhibited significantly reduced BBB locomotor scores and inclined plane test performance at 1,2 and 4 weeks post-operation(P＜0.05);obvious tissue cavitation,cellular edema and Prussian blue positive iron deposition in spinal cord tissues;downregulated protein and mRNA expressions of Nrf2,SLC7A11,GPX4,HO-1(P＜0.05);and upregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).Compared to the model group,the Jisuishang Formula and Fer-1 intervention groups showed significantly improved BBB scores and inclined plane test result at 1,2 and 4 weeks post-operation(P＜0.05);reduced tissue cavitation,attenuated cellular edema and decreased Prussian blue positive iron deposition in spinal cord tissues;upregulated protein and mRNA expression of Nrf2,SLC7A11,GPX4 and HO-1 in spinal cord tissues(P＜0.05);and downregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).CONCLUSION Targeting the Nrf2/SLC7A11/GPX4 signaling pathway,Jisuishang Formula potentially suppresses ferroptosis and alleviates iron accumulation in spinal cord neurons,thereby improving neurological recovery in CSM rats.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.

AIM To investigate the effects of Jisuishang Formula on neurological function and ferroptosis in a rat model of cervical spondylotic myelopathy(CSM).METHODS The CSM rat models were established and randomly assigned to the model group,the Fer-1 group(2 g/kg Ferrostatin-1 via intraperitoneal injection),the low-dose(9.7 g/kg,intragastrically),medium-dose(19.4 g/kg,intragastrically)and high-dose(38.8 g/kg,intragastrically)Jisuishang Formula groups,and the sham operation group,with 6 rats in each group.Following 4 weeks of treatment administration,BBB locomotor scores and oblique plate test result were recorded to assess their neurological function in rats.Histopathological evaluation utilized HE staining for spinal cord tissue pathology,Nissl staining for Nissl body visualization,and Prussian blue staining for iron ion deposition analysis.Protein expressions of Nrf2,SLC7A11,GPX4,HO-1,TFRC and Cox2 in spinal cord tissues was detected by immunofluorescence and Western blot,while mRNA expressions were quantified using RT-qPCR.RESULTS Compared to the sham group,the CSM model group exhibited significantly reduced BBB locomotor scores and inclined plane test performance at 1,2 and 4 weeks post-operation(P＜0.05);obvious tissue cavitation,cellular edema and Prussian blue positive iron deposition in spinal cord tissues;downregulated protein and mRNA expressions of Nrf2,SLC7A11,GPX4,HO-1(P＜0.05);and upregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).Compared to the model group,the Jisuishang Formula and Fer-1 intervention groups showed significantly improved BBB scores and inclined plane test result at 1,2 and 4 weeks post-operation(P＜0.05);reduced tissue cavitation,attenuated cellular edema and decreased Prussian blue positive iron deposition in spinal cord tissues;upregulated protein and mRNA expression of Nrf2,SLC7A11,GPX4 and HO-1 in spinal cord tissues(P＜0.05);and downregulated protein and mRNA expressions of TFRC and Cox2(P＜0.05).CONCLUSION Targeting the Nrf2/SLC7A11/GPX4 signaling pathway,Jisuishang Formula potentially suppresses ferroptosis and alleviates iron accumulation in spinal cord neurons,thereby improving neurological recovery in CSM rats.

Objective To assess the effectiveness and safety of prone positioning in the treatment of neonatal respiratory distress syndrome(NRDS)using invasive respiratory support.Methods A prospective study was conducted from June 2020 to September 2023 at Suining County People's Hospital,involving 77 preterm infants with gestational ages less than 35 weeks requiring invasive respiratory support for NRDS.The infants were randomly divided into a supine group(37 infants)and a prone group(40 infants).Infants in the prone group were ventilated in the prone position for 6 hours followed by 2 hours in the supine position,continuing in this cycle until weaning from the ventilator.The effectiveness and safety of the two approaches were compared.Results At 6 hours after enrollment,the prone group showed lower arterial blood carbon dioxide levels,inspired oxygen concentration,oxygenation index,rates of tracheal intubation bacterial colonization,and Neonatal Pain,Agitation and Sedation Scale scores compared to the supine group(P<0.05).There were no significant differences between the groups in terms of pH,arterial oxygen pressure,positive end-expiratory pressure,duration of mechanical ventilation,accidental extubation,ventilator-associated pneumonia,air leak syndrome,skin pressure sores,feeding intolerance,and grades II-IV intraventricular hemorrhage(P>0.05).Conclusions Compared to supine positioning,prone ventilation effectively improves oxygenation,increases comfort,and reduces tracheal intubation bacterial colonization in neonates requiring mechanical ventilation for NRDS,without significantly increasing adverse reactions.

Objective: To evaluate the success rate of His-Purkinje system pacing (HPSP) in patients with various sites of atrioventricular block (AVB) and provide clinical evidence for the selection of HPSP in patients with AVB. Methods: This is a retrospective case analysis. 637 patients with AVB who underwent permanent cardiac pacemaker implantation and requiring high proportion of ventricular pacing from March 2016 to September 2021 in the Department of Cardiology, General Hospital of Northern Theater Command were enrolled. The site of AVB was determined by electrophysiological examination. His bundle pacing (HBP) was performed in the first 130 patients (20.4%) who were classified as the HBP group and HPSP included HBP and/or left bundle branch pacing (LBBP) was performed in later 507 patients (79.6%) and these patients were classified as the HPSP group. The basic clinical information such as age and sex of the two groups was compared, and the success rates of HBP or HPSP in patients with different sites of AVB and QRS intervals were analyzed. Results: The age of HBP group was (66.4±15.9) years with 75 males (57.7%). The age of HPSP group was (66.8±13.6) years with 288 (56.8%) males. Among 637 patients, 63.0% (401/637) had atrioventricular node block; 22.9% (146/637) had intra-His block; 14.1% (90/637) had distal or inferior His bundle block. Totally, the success rate of HPSP was higher than that of HBP [93.9% (476/507) vs. 86.9% (113/130), P<0.05]. In each group of patients with various AVB sites, the success rate of HPSP was higher than that of HBP respectively and both success rates of HBP and HPSP showed a declining trend with the distant AVB site. The success rate of HBP in patients with atrioventricular node block and intra-His block was higher than that in patients with distal or inferior His bundle block [95.2% (79/83) vs. 47.1% (8/17), P<0.001; 86.7% (26/30) vs. 47.1% (8/17), P=0.010]. The success rate of HPSP was higher than that of HBP in patients with distal or inferior His bundle block [87.7% (64/73) vs 47.1% (8/17), P=0.001]. In patients with QRS<120 ms, 94.9% (520/548) of AVB sites were in atrioventricular node or intra-His, and HBP had a similar high success rate with HPSP [95.6% (109/114) vs. 96.3% (418/434), P=0.943] in these patients. In patients with QRS ≥ 120 ms, 69.7% (62/89) of AVB sites were at distal or inferior His bundle, and the success rate of HBP was only 25.0% (4/16), while the success rate of HPSP was as high as 79.5% (58/73), P<0.001. Conclusions: In patients with QRS<120 ms and atrioventricular node block or intra-His block, success rates of HBP and HPSP are similarly high and HBP might be considered as the first choice. In patients with QRS ≥ 120 ms and AVB site at distal or inferior His bundle, the success rate of HPSP is higher than that of HBP, suggesting LBBP should be considered as the first-line treatment option.
Aged ; Aged, 80 and over ; Atrioventricular Block/therapy* ; Bundle of His/physiology* ; Cardiac Pacing, Artificial ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.
End Stage Liver Disease ; Follow-Up Studies ; Humans ; Liver Cirrhosis/drug therapy* ; Middle Aged ; Peripheral Blood Stem Cells ; Severity of Illness Index ; Treatment Outcome

Genipin (Gen) is an important antioxidant that plays a crucial role in the process of intracellular resistance to oxidative stress. In order to study the effect of genipin on MIN6 cells injured by high glucose, the CCK-8 method was used to detect the cell survival rate. The cell viability of the high-glucose injury group decreased (P <0. 05). But after genipin acted on the cells injured by high glucose, the cell viability increased (P <0. 05). The mouse insulin detection kit and ATP content detection kit found that the insulin release in the high glucose injury group decreased (P < 0. 001) and the ATP content decreased (P <0. 001). After genipin was given, the insulin release increased (P <0. 01), ATP content increased (P <0. 01). The fluorescent probe DCFH-DA detected the intracellular reactive oxygen species (ROS) level and found that the ROS content in the high glucose-injury group was significantly increased (P <0. 01). After genipin was administered, ROS content decreased (P < 0. 05). Glutathione(GSH) / oxidized glutathione (GSSG), intracellular malondialdehyde (MDA), superoxide dismutase(SOD) and catalase (CAT) and lactate dehydrogenase (LDH) activity in the cell supernatant revealed that the GSH / GSSH ratio, SOD and CAT levels in the high glucose injury group decreased (P <0. 05), and the intracellular MDA and LDH levels were significant increased (P<0. 001) .After administration of genipin, the GSH / GSSH ratio, SOD and CAT levels increased (P <0. 01), MDA and LDH levels were significantly reduced (P <0. 01). Mitochondrial membrane potential (MMP) levels decreased in the highglucose injury group (P <0. 01). After genipin acted on the cells injured by high glucose, the MMP level increased (P < 0. 05). Western blot detected uncoupling protein 2 (UCP2), antioxidative proteinsglutathione reductase (GR) and glutaredoxin 1 (Grx1) contents. The results showed that UCP2 contents in the high glucose injury group increased (P <0. 01) and the content of oxidized protein decreased (P < 0. 01). After genipin was administered, the expression of UCP2 decreased (P < 0. 05), and the expression of antioxidative protein increased (P < 0. 05). Experiments suggest that genipin has anantioxidant protective effect on MIN6 cells damaged by high glucose and maintains the function of MIN6cells to promote insulin secretion. This experiment provides experimental data for the antioxidation of genipin on MIN6 cells injured by high glucose, and also provides new ideas for the follow-up study of genipin in the treatment and prevention of diabetes.

Alcohol liver disease (ALD) has become a global threat to human health. It is associated with a wide range of liver diseases including alcohol fatty liver, steatosis, fibrosis and cirrhosis, and finally leads to liver cancer and even death. Centranthera grandiflora is a traditional Chinese medicinal herb commonly used to treat ALD, but no research about its mechanism is available. This study evaluated the hepatoprotective effect and mechanism of C. grandiflora against alcohol-induced liver injury in mice. We found that the ethanol extracts of C. grandiflora (CgW) alleviated the alcohol-induced liver injury, enhanced the levels of antioxidant enzymes, and reduced the amount of lipid peroxides. CgW also affected cell apoptosis by inhibiting the activity of Bax, cleaved-caspase 3 and cleaved-caspase 9, and increasing the activity of Bcl-2. In conclusion, the results showed that CgW can effectively improve ALD through alleviating oxidative stress and inhibiting cell apoptosis for the first time. This study suggested that C. grandiflora is a promising herbal medicine for ALD treatment.
Animals ; Apoptosis ; Chemical and Drug Induced Liver Injury, Chronic ; Ethanol ; Humans ; Liver ; Liver Diseases, Alcoholic ; Mice ; Oxidative Stress

Morinda officinalis oligosaccharides (MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin (5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan; meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation, and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide, as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.