Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

Kidney-Yang deficiency syndrome is a common geriatric disease that underlies chronic conditions such as diabetic nephropathy, chronic kidney disease, and osteoporosis. As age progresses, the kidney-Yang deficiency syndrome showcases increasingly pronounced manifestations, emerging as a key factor in the comorbidities experienced by elderly patients and affecting their quality of life and overall health status. Traditional Chinese medicine(TCM) has been extensively utilized in the treatment of kidney-Yang deficiency syndrome, with Epimedii Folium, Cinnamomi Cortex, and Lycii Fructus widely used in clinical settings. Despite the complexity of the molecular mechanisms involved in treating kidney-Yang deficiency syndrome, the potential therapeutic value of TCM remains compelling. Delving into the mechanisms of TCM treatment of kidney-Yang deficiency syndrome by regulating the neuro-endocrine-immune system can provide a scientific basis for targeted treatments of this syndrome and lay a foundation for the modernization of TCM. The pathophysiology of kidney-Yang deficiency syndrome involves multiple systems, including the interaction of the neuro-endocrine-immune system, the decline in renal function, the intensification of oxidative stress responses, and energy metabolism disorders. Understanding these mechanisms and their interrelationships can help untangle the etiology of kidney-Yang deficiency syndrome, aiding clinicians in making more precise diagnoses and treatments. Furthermore, the research on the specific applications of TCM in research on these pathological mechanisms can enhance the international recognition and status of TCM, enabling it to exert a greater global influence.
Humans ; Yang Deficiency/physiopathology* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Kidney Diseases/physiopathology* ; Neurosecretory Systems/physiopathology* ; Animals ; Kidney/physiopathology* ; Endocrine System/physiopathology* ; Immune System/physiopathology*

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 investigate the dosimetric characteristics of intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT) in typical head and neck malignant tumors.Methods:Three types of typical head and neck tumors (nasopharyngeal carcinoma, parotid gland carcinoma, laryngeal carcinoma) treated at Shandong Cancer Hospital and Institute from December 2023 to December 2024 were taken as research subjects. IMPT and VMAT radiotherapy plans were created according to clinical prescription requirements of target and organs at risk limits respectively. The conformity index (CI), homogeneity index (HI) and gradient index (GI) for target coverage of two radiotherapy plans were evaluated for 3 patients, as well as the dosimetric indicators of organs at risk.Results:The CI of IMPT for nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma were 0.70, 0.72 and 0.67, respectively. The HI were 0.11, 0.08 and 0.08, respectively. The GI were 3.08, 2.49 and 3.75, respectively. The CI of VMAT plans were 0.77, 0.82 and 0.91, respectively. The HI were 0.12, 0.10 and 0.04, respectively. The GI were 3.67, 2.63 and 3.45, respectively. The results showed that CI of IMPT plan was slightly lower than that of VMAT plan, and HI of IMPT plan was comparable to that of VMAT plan, the GI of the IMPT plan for patients with nasopharyngeal carcinoma and parotid gland carcinoma was lower than that of the VMAT plan, and the GI of the IMPT plan for patient with laryngeal carcinoma was higher than that of the VMAT plan, and all were within the clinically acceptable range. The IMPT plan has demonstrated significant dose advantages in the treatment of nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma. For patient with nasopharyngeal carcinoma, the IMPT plan reduced the D max of the left and right crystals by 54.1% and 50.4%, respectively, compared to VMAT plan, and reduced the D mean of the oral and laryngeal tissues by 40.5% and 49.6%, respectively. For patient with parotid gland carcinoma, IMPT plan reduced the D max of the brainstem and spinal cord by 66.2% and 40.5%, respectively, compared to VMAT plan. For patient with laryngeal carcinoma, IMPT reduced spinal cord D max by 77.0%, while thyroid cartilage D mean increased by 8.0% compared to VMAT plan. For the additional dose in the patients' body, taking the absolute volumes occupied by the prescribed dose areas of 10%, 30%, and 50% in the patients' body as examples, IMPT plan of nasopharyngeal carcinoma patient decreased by 29.7%, 29.6%, and 34.9% compared to VMAT plan, respectively. IMPT plan of parotid gland carcinoma patient decreased by 61.0%, 39.7%, and 17.4% compared to VMAT plan, respectively. IMPT plan of laryngeal carcinoma patient decreased by 63.9%, 31.7%, and 4.1% compared to VMAT plan, respectively. Conclusions:Compared with VMAT plan, IMPT plan can effectively reduce the irradiation dose of most organs at risk near the target of head and neck tumors, but the dose of string organs close to the target area may be higher, which needs attention.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

To investigate the transcriptionally regulatory mechanism of the senp8 promoter in yellow cat-fish(Pelteobagrus fulvidraco);this study used P.fulvidraco as the research subject.Dual-luciferase re-porter assay and electrophoretic mobility shift assay were employed to analyze the functional activity of the promoter;coupled with in vivo experiments.The results indicated that the 2 045 bp senp8 promoter se-quence contained key transcription factor binding sites such as SP1;TATA-Box;CCAAT-Box;SREBP1;PPARα;and PPARγ.The binding sites of SREBP1(-901/-910 bp);PPARα(-1 291/-1 308 bp);and PPARγ(-1 292/-1 306 bp)in the senp8 promoter positively regulate its activity;and oleic acid or palmitic acid promote this binding.Furthermore;high-fat feeding promoted the expression of the senp8 gene and its protein in the liver of P.fulvidraco;oleic acid or palmitic acid treatment significantly en-hanced the activity of the senp8 promoter;and this enhancement could be achieved through the regulatory effects of SREBP1;PPARα;and PPARγ response elements.Additionally;high-fat feeding influenced the mRNA and protein expression levels of genes related to deSUMOylation modification in the liver of P.fulvidraco.This study provides new insights into the relationship between deSUMOylation modification and the regulation of lipid metabolism in the vertebrates.

Objective To study whether electroacupuncture(EA)attenuates traumatic brain injury(TBI)by down-regulating glutamate carboxypeptidase Ⅱ(GCPII)gene expression in rats.Methods Rats were divided into Sham group(n=10),TBI group(n=11),TBI+EA group(n=11),TBI+EA+GCPII-NC group(n=11)and TBI+EA+GCPII-OE group(n=11).Sham group rats underwent sham surgery,while other groups rats underwent TBI modeling using an electronic brain injury instrument.The rats in Sham group and TBI group were fed normally,and the rats in other groups were treated with electroacupuncture for 14 days.On the basis of electroacupuncture treatment,rats in TBI+EA+GCPII-NC group and TBI+EA+GCPII-OE group were injected with GCPII-NC and GCPII-OE,respectively.After treatment,the cognitive function of rats was evaluated by neurological function score and Morris water labyrinth task.HE and TUNEL staining were performed on brain tissue.The water content,glutamate(Glu)content,calcium(Ca2+)concentration,superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in brain tissue of rats in each group were measured.The mRNA or protein expression of GCPII,Bax,Bcl2 and cleaved caspase-3 in brain tissue were detected by qRT-PCR or Western blot.Results Compared with Sham group,the expression of mRNA and protein of GCPII in TBI group increased,the neurological function score and escape latency increased,the number of crossing the platform decreased,the water content increased,the cortex showed obvious damage,the content of Glu increased,the concentration of calcium increased,the levels of SOD,CAT and GSH-Px decreased,the level of MDA increased,the positive rate of TUNEL increased,the expression of Bax and cleaved caspase-3 protein increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Compared with TBI group,the expression level of mRNA and protein of GCPII in TBI+EA group decreased,the neurological function score and escape latency decreased,the number of crossing platform increased,the water content decreased,the morphology of cortex improved obviously,the content of Glu decreased,the concentration of calcium decreased,the level of SOD,CAT and GSH-Px increased,the level of MDA decreased,the positive rate of TUNEL decreased,the expression level of Bax and cleaved caspase-3 protein decreased,and the expression level of Bcl2 protein increased significantly(P<0.05).Compared with TBI+EA group and TBI+EA+GCPII-NC group,the expression level of mRNA and protein of GCPII in TBI+EA+GCPII-OE group increased,neurological function score and escape latency increased,the number of crossing platform decreased,water content increased,cortical injury aggravated,Glu content increased,calcium concentration increased,SOD,CAT and GSH-Px levels decreased,MDA level increased,TUNEL positive rate increased,Bax and cleaved caspase-3 protein expression increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Conclusion By down-regulating the expression of GCPII gene,electroacupuncture reduced the content of glutamate in the brain tissue of TBI rats,thereby inhibiting calcium overload,oxidative stress and neuronal apoptosis in the brain tissue,and thereby improving cognitive function and alleviating brain injury.

Objective To study whether electroacupuncture(EA)attenuates traumatic brain injury(TBI)by down-regulating glutamate carboxypeptidase Ⅱ(GCPII)gene expression in rats.Methods Rats were divided into Sham group(n=10),TBI group(n=11),TBI+EA group(n=11),TBI+EA+GCPII-NC group(n=11)and TBI+EA+GCPII-OE group(n=11).Sham group rats underwent sham surgery,while other groups rats underwent TBI modeling using an electronic brain injury instrument.The rats in Sham group and TBI group were fed normally,and the rats in other groups were treated with electroacupuncture for 14 days.On the basis of electroacupuncture treatment,rats in TBI+EA+GCPII-NC group and TBI+EA+GCPII-OE group were injected with GCPII-NC and GCPII-OE,respectively.After treatment,the cognitive function of rats was evaluated by neurological function score and Morris water labyrinth task.HE and TUNEL staining were performed on brain tissue.The water content,glutamate(Glu)content,calcium(Ca2+)concentration,superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in brain tissue of rats in each group were measured.The mRNA or protein expression of GCPII,Bax,Bcl2 and cleaved caspase-3 in brain tissue were detected by qRT-PCR or Western blot.Results Compared with Sham group,the expression of mRNA and protein of GCPII in TBI group increased,the neurological function score and escape latency increased,the number of crossing the platform decreased,the water content increased,the cortex showed obvious damage,the content of Glu increased,the concentration of calcium increased,the levels of SOD,CAT and GSH-Px decreased,the level of MDA increased,the positive rate of TUNEL increased,the expression of Bax and cleaved caspase-3 protein increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Compared with TBI group,the expression level of mRNA and protein of GCPII in TBI+EA group decreased,the neurological function score and escape latency decreased,the number of crossing platform increased,the water content decreased,the morphology of cortex improved obviously,the content of Glu decreased,the concentration of calcium decreased,the level of SOD,CAT and GSH-Px increased,the level of MDA decreased,the positive rate of TUNEL decreased,the expression level of Bax and cleaved caspase-3 protein decreased,and the expression level of Bcl2 protein increased significantly(P<0.05).Compared with TBI+EA group and TBI+EA+GCPII-NC group,the expression level of mRNA and protein of GCPII in TBI+EA+GCPII-OE group increased,neurological function score and escape latency increased,the number of crossing platform decreased,water content increased,cortical injury aggravated,Glu content increased,calcium concentration increased,SOD,CAT and GSH-Px levels decreased,MDA level increased,TUNEL positive rate increased,Bax and cleaved caspase-3 protein expression increased,and the expression of Bcl2 protein decreased significantly(P<0.05).Conclusion By down-regulating the expression of GCPII gene,electroacupuncture reduced the content of glutamate in the brain tissue of TBI rats,thereby inhibiting calcium overload,oxidative stress and neuronal apoptosis in the brain tissue,and thereby improving cognitive function and alleviating brain injury.

Objective:To investigate the effect of remote ischemic conditioning (RIC) on cerebral perfusion and functional outcome in patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to the Department of Neurology, the Second Affiliated Hospital of Xuzhou Medical University from November 2023 to July 2024 were included prospectively. They were randomly divided into RIC group and control group within 48 hours of onset. The control group received treatment according to the current treatment guidelines, while the RIC group received RIC based on this. At admission, three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) perfusion imaging technology was used to measure the cerebral blood flow and calculate low perfusion regions volume with corrected cerebral blood flow (cCBF) <20 and <30 ml/(100 g·min), respectively; and then 3D-pCASL perfusion imaging was performed again on the 10 th day of admission. The main outcome measure was the functional outcome evaluated using the modified Rankin Scale at 90 days after onset. 0-1 were defined as excellent outcome, 0-2 were defined as good outcome, and >2 was defined as poor outcome. Secondary outcome measures included the National Institutes of Health Stroke Scale (NIHSS) score at 14 days after onset and their changes from baseline, cerebral perfusion parameters and their changes, early neurological deterioration (END), hemorrhagic transformation (HT), and adverse reactions of RIC. Results:A total of 48 patients completed the test and follow-up, of which 32 patients (66.7%) were male, aged 67.60±7.37 years. The median baseline NIHSS score was 3 (interquartile range, 2-5). Etiological classification: 15 patients (31.3%) were large artery atherosclerosis, 28 (58.3%) were small vessel occlusion and 5 (10.4%) were other causes. Thirty-one patients (64.6%) were anterior circulation stroke. Among the 48 patients, there were 28 in the RIC group and 20 in the control group. The time from onset to RIC in the RIC group was 21.89±16.17 hours. There was no significant difference in demographic and baseline data between the RIC group and the control group (all P>0.05). The proportion of patients with excellent outcome (78.6% vs. 50.0%; P=0.038) and good outcome (89.3% vs. 60.0%; P=0.042) in the RIC group at 90 days were significantly higher than those in the control group. The NIHSS score and changes at 14 days were also significantly better than those in the control group (all P<0.05). In addition, the volume of low perfusion region with cCBF <20 and <30 ml/ (100 g·min) in the RIC group after treatment decreased compared to the baseline, while the control group slightly enlarged, and the difference between the two groups was statistically significant ( P<0.05). There was no significant difference in the incidence of END and HT between the RIC group and the control group (all P>0.05). Multivariate logistic regression analysis showed that RIC was an independent protective factor for good outcome (odds ratio 9.182, 95% confidence interval 1.579-53.401; P=0.014) and excellent outcome (odds ratio 9.982, 95% confidence interval 1.257-79.230; P=0.030) at 90 days. There were no serious adverse reactions observed in the RIC group. Conclusion:RIC can reduce the volume of low perfusion region in patients with AIS, improve neurological function and clinical outcome, and has no serious adverse reactions.

Objective To study and verify the function of de novo interferon regulatory factor(IRF8)frameshift mutation detected in an etiology screening of the cohort of children with recurrent pneumonia at the molecular level.Methods The recombinant overexpression plasmids with wildtype or mutated IRF8 genes were constructed to transiently transfect HEK293T cells,or packed into lentivirus to infect two kinds of immune cell lines.Q-PCR,Western blot,immunofluorescence and other experimental assays were performed to explore the differences of expression and the regulatory effect on downstream genes associated with inflammation.Results The recombinant vectors with wildtype or mutated IRF8 genes were constructed successfully,and the efficiency of transfection by plasmids and infection by packed lentivirus was remarkable as well.Compared with wildtype,the molecular weight of IRF8 variant was slightly increased,while the expression level presents in opposition,even if on transcription level.Moreover,the localization of IRF8 variant was detected in abundance in nucleus rather than cytoplasm,and its inhibition effect was enhanced on the downstream ISRE element in comparison with the wildtype IRF8 protein.Conclusion The de novo frameshift mutation was presumed as gain-of-function(GOF)mutation.