ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

OBJECTIVE To investigate the mechanism by which Naozhenning granules （NZN） improve learning and memory impairment in a rat model of multiple cerebral concussion （MCC）. METHODS The MCC rat model was established using the closed controlled cortical impact method. The experiment was set up with a blank group （normal saline）， a model group （normal saline）， a piracetam group （positive control group， 0.324 g/kg）， and high-， medium-， and low-dose NZN groups （5.4， 2.7， 1.35 g/kg）， with 11 rats in each group. Drugs or normal saline were administered by gavage once daily for 28 consecutive days. General condition and body weight were monitored throughout the experiment. The sucrose preference rate and novel object recognition index were measured； Evans blue （EB） extravasation in the cerebral cortex was detected； pathological changes of cortical neurons were observed； the levels of B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the cerebral cortex were determined； and the phosphorylation levels of AMP-activated protein kinase （AMPK）， glycogen synthase kinase 3β （GSK3β）， and Tau protein were detected. RESULTS Compared with the blank group， the model group showed poor mental state， sluggish response to external stimuli， reduced food and water intake， decreased limb flexibility， and disheveled fur. Body weight， sucrose preference rate， and novel object recognition index were significantly decreased （ P ＜0.05）； EB extravasation in the cerebral cortex was significantly increased （ P ＜0.05）， with severe neuronal damage. The positive area ratio of Bax protein， IL-6 and TNF-α levels， and Tau protein phosphorylation level were all significantly increased （ P ＜0.05）， whereas the positive area ratio of Bcl-2 protein， IL-10 level， and AMPK and GSK3β protein phosphorylation levels were significantly decreased （ P ＜0.05）. Compared with the model group， all NZN dose groups showed improvements in general condition and pathological damage， with quantitative indices partially restored， and the differences in quantitative indices in high-dose NZN group were statistically significant （ P ＜0.05）. CONCLUSIONS NZN can effectively improve learning and memory impairment in MCC model rats. The mechanism may be related to activating the AMPK/GSK3β pathway， inhibiting inflammatory response， reducing Tau protein phosphorylation level， and then repairing the neuronal injury.

Objective To explore the efficacy of the on-demand intermittent total androgen blockade regimen in treating cases with positive surgical margins after radical prostatectomy for pT3 stage prostate cancer. Methods A retrospective analysis was conducted on the clinical data of 21 patients with pT3 stage prostate cancer who underwent radical prostatectomy and had positive surgical margins confirmed by pathology in our hospital during Jan. 2013 and Dec. 2020. Prostate-specific antigen(PSA)was used as the indicator of observation. For those with biochemical recurrence(PSA＞0.2 μg/L), at least 2 months of androgen deprivation therapy(ADT)combined with the maximum androgen receptor antagonist was administered for maximal androgen blockade endocrine therapy. If PSA still exceeded 0.1 μg/L after 2 months of maximal androgen blockade treatment, the maximal androgen blockade was maintained and monthly follow-up was conducted until PSA reached the discontinuation criteria. During the discontinuation period, the serum PSA and testosterone levels were checked every 4 to 6 weeks. The time of application of maximal androgen blockade and the subsequent interval of discontinuation were defined as one treatment cycle. Results Postoperative pathology confirmed that among the 21 patients, 17 were pT3a and 4 were pT3b. The PSA level 1 month after surgery was(0.23±0.45)μg/L. The follow-up lasted for 48 to 126 months, with an average of(68.86 ± 20.43)months. The interval between the first application of maximal androgen blockade and radical prostatectomy was 2 to 35 months, with an average of(12.48±8.83)months. One patient died of post-cerebral infarction complications 74 months after surgery, another progressed to hormone-resistant prostate cancer(CRPC)70 months after surgery and the treatment plan was immediately changed. Up to 90.5%(19/21)of the patients completed 5 to 12 cycles of combined endocrine therapy, with no tumor progression. Conclusion Based on the postoperative PSA level monitored, intermittent administration of the maximum androgen blockade endocrine therapy can effectively control the cancer progression of patients with positive surgical margins after radical prostatectomy, which can also reduce the adverse reactions.

ObjectiveTo investigate the metabolic mechanisms of Limosilactobacillus reuteri （L. reuteri） in alleviating chemotherapy-induced intestinal mucosal injury （CIMI）. MethodsC57BL/6 mice were randomly divided into the Control group， Model group， and L. reuteri treatment group （n=8 per group）. Mice in the L. reuteri group were intragastrically administered L. reuteri （1 × 10⁹ CFU/mL） for 10 consecutive days. From day 5， mice in the Model and L. reuteri groups were intraperitoneally injected with 5-FU （65 mg/kg） for 6 consecutive days to establish a CIMI model. Body weight changes， colon length， and related indicators were recorded. Intestinal histopathological injury was assessed by HE staining with measurement of villus height and crypt depth. The expression levels of zonula occludens-1 （ZO-1）， Occludin， Claudin-4， Muc1， and Muc2 in ileal tissues were determined by RT-qPCR and immunohistochemistry to evaluate intestinal barrier function. In addition， untargeted metabolomics was performed on cecal contents from each group to analyze metabolic profiles and enrichment of differential metabolic pathways. ResultsL. reuteri intervention significantly alleviated body weight loss （P<0.001） and colon shortening （P<0.05） in CIMI mice， effectively reducing ileal tissue pathological damage， and upregulating the expression of ZO-1， Occludin， Claudin4， Muc1， and Muc2 （P<0.05）. Untargeted metabolomics analysis showed that L. reuteri treatment reversed the abnormal metabolic profile in the cecal contents of CIMI mice， bringing it closer to normal. Various differential metabolites， such as acylcarnitines and polyunsaturated fatty acids， might play an important role in L. reuteri-mediated alleviation of CIMI. These differential metabolites were primarily enriched in key pathways such as linoleic acid metabolism， tryptophan metabolism， and unsaturated fatty acid biosynthesis. ConclusionThis study reveals that L. reuteri improves intestinal barrier function and alleviates CIMI by regulating the intestinal metabolic profile， particularly lipid and amino acid metabolism. It provides a novel potential strategy for the prevention and treatment of CIMI.

ObjectiveTo explore the ameliorative effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid （4-PBA） on bile acid metabolism disorders induced by bacterial lipopolysaccharide （LPS） in late-pregnant mice， and to clarify the regulatory mechanism of endoplasmic reticulum stress （ERS） in intrahepatic cholestasis of pregnancy （ICP）. MethodsTwenty-four pregnant mice were divided into control group， LPS group， 4-PBA group， and LPS+4-PBA group. On the 16th day of pregnancy， the LPS group received intraperitoneal injection of LPS （200 μg/kg） and the 4-PBA group received injection of 4-PBA （150 mg/kg）. In the LPS+4-PBA group， 4-PBA was intraperitoneally injected first， followed by LPS administration 1 h later. Serum total bile acid （TBA）， liver injury markers， bile acid profiles， and the expression of key genes and proteins were detected 6 h after LPS treatment. ResultsLPS exposure increased serum TBA levels in pregnant mice（P<0.05）， activated ERS markers and inflammatory factors， and downregulated bile acid transporters and the expression of the rate limiting enzyme CYP7A1（all P<0.05）. 4-PBA intervention effectively inhibited ERS， reduced TBA levels（P<0.05）， and upregulated Ntcp， Bsep， Mdr3， and Mrp3 gene expression（all P<0.05）. ConclusionERS plays an important role in LPS interference with the homeostasis of bile acid metabolism during pregnancy. Inhibiting ERS can improve bile stasis by regulating bile acid transporters， providing a theoretical basis for targeted therapy of ICP.

Community- and home-based integrated elderly care and medical services represents the development direction of the integrated elderly care and medical services model. Achieving balanced development of both service supply and demand， and enhancing the overall governance effectiveness of services， are essential for the aging society governance. Taking XJ comprehensive elderly care service center in J district， N city as an example， this paper found the main reasons for the service supply-demand contradiction in urban community- and home-based integrated elderly care and medical services by adopting case studies and in-depth interview methods， including insufficient social awareness of the services and low scientific level of policies； low trust of service demanders and insufficient willingness to pay autonomously； and insufficient initiative of service providers and prominent administrative governance characteristics. Through the deduction of emotional governance theory， it was believed that under the consensus of high collaboration and synergy between the government and all sectors of society， emotional interaction among multiple participating subjects can be strengthened by the organic combination of the three levels of spiritual governance， emotional governance， and emotional labor， so as to build an efficient emotional governance system of community- and home-based integrated elderly care and medical services.

ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg^-1） and high-dose CRZG （1.638 g·kg^-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg^-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ_1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ_1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ_1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.

The relationship between gut microbiota and depressive disorder has become a research focus in recent years. Within the microbiota-gut-brain axis, the gut microbiota influences the onset and progression of depressive disorder primarily through the tryptophan metabolic pathway. Tryptophan, an essential amino acid in humans, is subject to dual regulation by intestinal microorganisms, which modulate its metabolic balance via inflammatory stimulation and microbial metabolite production. In depression, excessive activation of the kynurenine branch of tryptophan metabolism leads to the accumulation of proinflammatory and neurotoxic metabolites, thereby exacerbating neuroinflammation in the brain. Intervention studies indicate that the antidepressant-like effects of probiotics and traditional Chinese medicine are associated with remodeling of the gut microbiota, restoration of tryptophan metabolic balance, and alleviation of neuroinflammation. Furthermore, targeted inhibition of kynurenine 3-monooxygenase can mitigate neuroinflammation by regulating microglial activity, thus improving depressive-like behaviors. In summary, the metabolite-inflammation axis represents a central node in the interaction regulation between tryptophan metabolism and the microbiota-gut-brain axis. This provides a theoretical foundation for developing novel therapeutic strategies targeting depression through modulation of gut microbiota-mediated tryptophan metabolism.
Tryptophan/metabolism* ; Gastrointestinal Microbiome/physiology* ; Humans ; Depressive Disorder/microbiology* ; Probiotics/therapeutic use* ; Brain/metabolism* ; Kynurenine/metabolism* ; Metabolic Networks and Pathways ; Animals ; Medicine, Chinese Traditional

Objective To explore strategies for further subdivision of DRG in gastrointestinal surgery cases,providing references to enhance the differentiation of DRG subgroups.Methods A total of 5 108 gastrointestinal surgery cases were selected from a tertiary grade A hospital and a tertiary hospital in Hubei Province,spanning from January 2019 to June 30,2023,and another secondary hospital's data from 2020 and 2021.It employs single factor analysis and multiple linear regression analysis to identify factors influencing case costs.Additionally,the opinions of nine clinicans were gathered regarding factors affecting resource consumption in gastrointestinal surgery cases.The four selected case groups were further subdivided considers the peak characteristics of disease costs.It compares subdivided groups with the DRG Payment Subgroups Scheme(Version 2.0).Results Groups GB1,GB2,GC1,and GC2 were subdivided into 7,4,7,and 6 DRG groups,respectively.The coefficient of variation of each subdivided DRG were reduced,homogeneity was increased,and inter-group differentiation was increased.The results were consistent with the DRG Payment Subgroups Scheme(Version 2.0).Conclusion Based on DRG grouping,the DRG groups can be further subdivided according to the peak characteristics presented by case costs.This subdivision strategy is helpful to provide new ideas for case grouping of Medicare payment.

Objective:To develop a method of employing flow cytometry to directly detect the γ-H2AX expression levels in peripheral blood lymphocytes of mice through fixation and lysis and to evaluate the feasibility of applying this method to research on the radiation-related biological effects and the efficacy evaluation of radioprotective drugs.Methods:A total of 41 male C57BL/6J mice were used. First, 21 mice were randomly divided into 7 groups according to different radiation doses (0, 1, 2, 4, 6, 8, and 10 Gy) with 3 mice in each group. Blood samples were collected from the tail vein of mice at 1, 4, 8, and 24 h after irradiation and immediately fixed with formaldehyde. Red blood cells (RBC) were lysed with Triton X-100, and γ-H2AX was labeled with specific antibodies. DRAQ5 dye was used to further exclude debris and anucleate cells. The mean fluorescence intensity of γ-H2AX in lymphocyte populations was directly analyzed by flow cytometry through forward and side scatter, and dose-effect curves after irradiation were established. Then, the other 20 mice were divided into radiation alone groups and radiation combined with WR-2721 administration groups at 4 and 6 Gy, respectively, with 5 mice in each group. Blood samples were collected from the tail vein of mice at 1, 4, 8, and 24 h after irradiation to detect the average fluorescence intensity of γ-H2AX in lymphocytes, which was used to evaluate the degree of DNA damage in mice and the therapeutic effect of WR-2721.Results:The expression of γ-H2AX in peripheral blood lymphocytes of mice significantly increased with the increase of radiation doses, and reached a peak at 1-2 h and then decreased. The dose-effect relationship was significant ( R2 = 0.9914). At 24 h after 4 and 6 Gy irradiation, compared with the radiation alone groups, the average fluorescence intensity of γ-H2AX in the radiation combined with WR-2721 administration groups was lower (144.8 ± 8.0 and 109.5 ± 9.7, vs. 178.0 ± 18.5 and 136.6 ± 5.4), with statistically significant difference ( t = 3.78, 5.48, P < 0.05). The average fluorescence intensity of γ-H2AX at 24 h after irradiation was consistent with the lowest values of the three blood cell lines at 7 or 14 d after irradiation. Conclusions:The application of flow cytometry with a fixation/dissolution protocol to directly detect the mean fluorescence intensity of γ-H2AX in peripheral blood lymphocytes of mice has significant application value in radiation biology effect research, radiation protection drug screening, and efficacy evaluation.