ObjectiveTo explore the effect of modified Ditan Decoction （涤痰汤） on chronic intermittent hypoxia cognitive function and the potential function mechanism. MethodsTwenty-four Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， and a modified Ditan Decoction group， with eight rats in each group. Rats in the modified Ditan Decoction group were administered the decoction by gavage at 14.8 ml/（kg·d）， while the normal group and the model group received the same dose of normal saline. Thirty minutes after daily gavage， the rats in all three groups were placed in an intermittent hypoxia chamber. The oxygen concentration for the model group and the modified Ditan Decoction group was adjusted daily for 8 hours using a computer program to establish the model， while the normal group was exposed to the same airflow rate of ambient air. The intervention was continued for 12 weeks to establish a chronic intermittent hypoxia rat model. The Y-maze test was used to evaluate spatial working memory in the rats. Resting-state functional magnetic resonance imaging （rs-fMRI） was performed to detect whole-brain regional homogeneity （ReHo） and seed-based functional connectivity （FC）. Brain regions showing significant differences in rs-fMRI were selected for further analysis. Immunofluorescence was used to detect β-amyloid （Aβ） deposition and the number of ionized calcium-binding adapter molecule 1 （IBA1）-positive microglial cells. Immunohistochemistry was employed to assess the expression of synaptophysin （SYP）， the excitatory synapse marker vesicular glutamate transporter 1 （Vglut1）， and the inhibitory synapse marker vesicular γ-aminobutyric acid transporter （VGAT）. ResultsCompared with the normal group， the model group showed a reduced spontaneous alternation rate in the Y-maze test. The smoothed Z-score standardized regional homogeneity （SzReHo） value in the left entorhinal cortex significantly increased， and the FC value from this seed point to the left basal forebrain significantly reduced. Additionally， the model group exhibited significantly higher Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， decreased expression of SYP， Vglut1， and VGAT， along with an increased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. Compared to the model group， the modified Ditan Decoction group demonstrated an increased spontaneous alternation rate， a significantly reduced SzReHo value in the left entorhinal cortex， and a significantly increased FC value from this region to the left basal forebrain. Furthermore， this group showed significantly lower Aβ fluorescence intensity and Iba1 positivity in the left entorhinal cortex， increased levels of SYP， Vglut1， and VGAT， and a decreased Vglut1/VGAT ratio （P＜0.05 or P＜0.01）. ConclusionModified Ditan Decoction can reconstruct the projection from the left basal forebrain to the entorhinal cortex in chronic intermittent hypoxia， thereby reducing Aβ aggregation and excessive microglial activation in the left entorhinal cortex. This process improves the excitation/inhibition imbalance caused by synaptic remodeling， ultimately enhancing cognitive function in rats of chronic intermittent hypoxia.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Purpose To investigate the expression and po-tential clinical value of heat shock protein 90α(Hsp90α)in co-lon adenocarcinoma.Methods The expression level of Hsp90αin colon adenocarcinoma and its relationship with clinicopatho-logical features,prognosis and immune cell infiltration were ana-lyzed by bioinformatics and immunohistochemistry.The prolifer-ation ability of colon cancer cells before and after Hsp90AA1 knockout was detected by CCK-8 cell proliferation assay and plate cloning assay.Results The bioinformatics tools showed that Hsp90AA1 was abnormally higher in colon cancer tissues than adjacent tissues,and the higher the expression level,the worse the prognosis of patients.The expression of Hsp90AA1 was positively correlated with the infiltration levels of CD4+T cells(Th2),CD8+T cells,myeloid inhibitory cells,Tregs cells,neutrophils,macrophages,M1 macrophages and M2 macropha-ges.Immunohistochemical results showed that the expression of Hsp90α in colon cancer tissues was significantly higher than in its adjacent tissues.The expression of Hsp90α was related to age(P＜0.05),not related to gender,tumor size,location,clini-cal classification,differentiation degree,tumor node metastasis,lympho-vascular invasion,perineural invasion(P＞0.05).The high expression of Hsp90α was an independent risk factor for the prognosis of colon cancer patients.The results of cell experi-ments showed that Hsp90AA1 knockout inhibited the growth and proliferation of colon cancer cells.Conclusion Hsp90α is highly expressed in colon adenocarcinoma,which may be a po-tential molecular marker for poor prognosis of colon adenocarci-noma.

Objective To establish a method to simultaneously determinate cobalt, nickel, arsenic, molybdenum, silver, cadmium and lead in blood and urine using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). Methods The blood samples were diluted 20 times with a mixed solution of nitric acid (0.10% V/V) and Triton X-100 (0.02% V/V). The urine samples were diluted 10 times with nitric acid (1.00% V/V). Yttrium-89, rhodium-103, and lutetium-175 were used as internal standards to decrease matrix interference, and either On-Mass mode or Mass-Shift mode was used to decrease mass spectrometry interference, with detection by ICP-MS/MS. Results The linear ranges of the seven elements were 0.100-10.000 μg/L, with the correlation coefficient >0.999 9. The detection limits for the seven elements in the blood and urine were 0.003-0.021 and 0.003-0.031 μg/L, respectively, and the minimum quantification limits were 0.009-0.064 and 0.009-0.094 μg/L, respectively. The recovery rates were 96.64%-102.90% and 96.34%-104.50% for the blood and urine, respectively. The within-run relative standard deviations (RSDs) were 0.32%-2.33% and 0.25%-2.31%, and the between-run RSDs were 1.07%-3.81% and 1.30%-3.62% for blood and urine, respectively. The samples were stable at 4 ℃ for at least 14 days. Conclusion ICP-MS/MS is a simple, sensitive, and accurate method for rapid detection of seven heavy metal elements in the blood and urine of occupational hazard-exposed workers.

Objective:To explore whether the degree of skeletal muscle atrophy in obese individuals under the influence of colorectal cancer is more severe than that in non-obese individuals.Methods:The clinical data of patients who underwent radical resection of colorectal cancer in our department from Jul 2020 to Dec 2021 was collected. Sixty-four obese patients were included and 64 non-obese patients were matched according to propensity score. At the same time, 51 obese patients were collected from non-tumor patients and matched with 51 non-obese patients. The psoas muscle index (PMI) of included patients was analyzed and compared.Results:The PMI of patients with colorectal cancer was significantly lower than that of corresponding non-tumor patients, regardless of gender and body weight (both P<0.05). The PMI of obese patients with colorectal cancer was significantly lower than that of non-obese patients ( P<0.05). Conclusions:The impact of colorectal cancer on skeletal muscle atrophy in obese individuals is greater than that in normal weight individuals. Therefore, the skeletal muscle status of obese patients with colorectal cancer should be evaluated more comprehensively.

Objective:To observe any effect of warm acupuncture on chondrocyte apoptosis and the miR-27a-mediated PI3K/AKT/mTOR signaling pathway using a rat model of early knee osteoarthritis (KOA).Methods:Fifty Sprague-Dawley rats were randomly divided into a control group, a model group, a warm acupuncture group, an inhibitor group, and an inhibitor + warm acupuncture group (the combined group), each of 10. Three days before the modeling, both the inhibitor and combined groups were injected with miR-27a inhibitor. Papain was then injected in all groups except the control group to establish the early KOA model. After successful modeling, the combined and warm acupuncture groups were given 30 minutes of warm acupuncture at the medial and lateral Xiyan points daily for 14 days. The model and inhibitor groups were fixed for 30 minutes during those sessions. After the 2 weeks, hematoxylin-eosin staining was used to observe any pathological changes in the cartilage tissue. Terminal deoxynucleoitidyl transferase-mediated nick end labeling was used to detect chondrocyte apoptosis, and enzyme-linked immunosorbent assays were employed to observe the levels of interleukin 1β (IL-1β) and IL-6. Western blotting was used to evaluate the expression of p-PI3K, p-AKT, p-mTOR, PI3K, AKT, mTOR, LC3-II, and Beclin1 proteins in the cartilage tissue, while quantitative real-time polymerase chain reactions detected the content of miR-27a.Results:After the intervention, the morphology of the chondrocytes in the warm acupuncture group had improved significantly compared to the model group, while that of the inhibitor and combined groups was better than among the warm acupuncture group. The rate of chondrocyte apoptosis in the warm acupuncture group was significantly lower than in the model group, while the rates of the inhibitor and combined groups were lower still. There was no significant difference between the inhibitor and the combination group on average. The average expression of IL-6, IL-1β, LC3-II and Beclin1 protein and of miR-27a were significantly lower in the warm acupuncture, inhibitor and combined groups than among the model group, with those of the inhibitor and combined groups significantly lower than among the warm acupuncture group, on average. The average p-PI3K/PI3K, p-AKT/AKT and p-mTOR/mTOR levels of the warm acupuncture, inhibitor and combined groups were significantly higher than those of the model group, with those of the inhibitor and combined groups significantly higher, on average, than among the warm acupuncture group. However, there was no significant difference between the inhibitor group and the combined group in their protein expression and mRNA levels.Conclusions:Warm acupuncture may down-regulate the expression of miR-27a to promote the activation of the PI3K/AKT/mTOR signaling pathway, inhibiting excessive autophagy and apoptosis. That would relieve inflammation and damage, and delay degeneration in early KOA, at least in rats.

Inflammatory bowel disease(IBD)is a chronic and relapsing inflammatory disorder of the gastrointestinal tract that poses a significant threat to human health.The pathogenesis of IBD remains unclear and is believed to involve various factors,including genetics,immune dysregulation,and environmental triggers.Recent evidence has highlighted the role of mitochondrial damage and dysfunction in the development of IBD.This article provides a comprehensive review and overview of studies related to the role of mitochondrial damage in IBD,focusing on the effects of mitochondrial oxidative stress damage,autophagy dysfunction,kinetic disturbances,and respiratory defects.The aim is to identify potential therapeutic targets and provide new insights for the scientific prevention and treatment of IBD.

Hereditary hemochromatosis is a rare autosomal genetic disorder that can cause multi-organ dysfunction in the liver,pancreas,spleen,heart and pituitary gland,with diverse clinical manifestations,make the diagnosis difficult.In recent years,with the deepening of clinical understanding and the development of genetic diagnosis tools,the diagnostic rate of this disease has increased significantly.In this paper,we report a case of hereditary hemochromatosis type 3 involving multiple organs and complicated by severe heart failure,aiming to improve the clinicians'understanding of this disease and reduce the leakage and misdiagnosis.

Objective:To explore the effect of identifying pelvic lymph nodes by different injection of indocyanine green (ICG) during fluorescent laparoscopic radical cystectomy.Methods:The data of 54 male bladder cancer patients admitted to the First Hospital of Shanxi Medical University from September 2021 to September 2022 were analyzed. Preoperative cystoscopic biopsy all revealed a pathological diagnosis of urothelial carcinoma. All patients underwent fluorescent laparoscopic radical cystectomy plus pelvic lymph node dissection.They were divided into 3 groups according to the annotated route: 6 in the medial malleolus injection group, 68(61, 73) years; 4 in the perineal injection group, 67(59, 74) years; 44 in the medial malleolus and perineum, 64(45, 78) in the combined injection group. Under general anesthesia, patients were placed in the supine position with 0.3 to 0.5 ml of subcutaneous ICG solution (2.5 mg/ml) injected from 1.0 to 1.5 h before surgery. In the medial malleolus injection group, 0.3 to 0.5 ml (0.75 mg/place) was injected at 2 cm above the medial malleolus and 0.3 to 0.5 ml (0.75 mg/place) at two symmetrical sites above the anus. Intraoperatively, 4K fluorescent laparoscopy was used to observe the color development of the injection site and lymphatic vessels in vitro, and then to observe the development of pelvic lymph nodes in vivo.Results:In 3 groups, inguinal lymph nodes were developed about 30 min after ICG injection, and 1 h later, the longest (4.5±0.3) h. The external iliac and common iliac lymph nodes, the obturatorius lymph nodes in the perineal injection group, and the inguinal, obturatorius, external iliac, internal, anterior sacral, and common iliac lymph nodes in the medial malleolar and perineal injection group. In this study, in 54 cases, the postoperative pathological examination confirmed that the removed fluorescently labeled tissue was lymph node tissue, and the lymph node detection rate was 100%. The postoperative stage was pT 2, 14, 32 pT 3 and 8 pT 4; 4 pNx, 44 pN 0, 5 pN 1and 1 pN 2. In the medial malleolar injection group, 2 patients staged pT 2, 3 stage pT 3, 1 stage pT 4; 1stage pNx stage, 4 stage pN 0 and 1 stage pN 1 stage. In the perineal injection group, 4 patients had postoperative pathological stage pT 3N 0; in the medial malleolar and perineal injection group, 12 pT 2, 25 and 7 pT 3; 3 pNx, 36 pN 0, 4 pN 1 and 1pN 2. Conclusions:ICG injection through the perineum and subcutaneous labeling of pelvic lymph nodes, and the simple malleolus or perineal injection can not completely develop the pelvic lymph nodes. The combined injection could fully develop the pelvic lymph nodes, which may accurately guide the operator to locate, identify and remove pelvic lymph nodes.

Objective To explore the effect and mechanism of esculin on hepatocyte steatosis by inhibiting protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2A(eIF2A)/activating transcription factor 4(ATF4)signaling pathway.Methods Human normal liver cell line HL-7702 was used to induce a fatty degeneration model of hepatocytes in vitro with 0.5mmol/L free fatty acid(FFA)(oleic acid∶palmitic acid=2∶1)and treated with 50μmol/L,200μmol/L esculin for 24h.After the cell samples were broken by ultrasound,the supernatant was collected and the contents of alanine transaminase(ALT),aspartate transaminase(AST),malondialdehyde(MDA),glutathione(GSH)and triacylglycerol(TG)were detected.Using Nile red fat fluorescence staining to detect intracellular lipid droplets;Quantitative reverse transcriptase-mediated polymerase chain reaction(qRT-PCR)was used to detect the transcription levels of genes related to intracellular lipid metabolism processes.Western blot(WB)was used to detect the protein expression levels of pro apoptotic factors Caspase-3 and Bax,as well as PERK/eIF2A/ATF4 signaling pathway related proteins and phosphorylation levels in cells.Results The results confirmed that treatments of 50μmol/L and 200μmol/L of esculin significantly decreased the levels of FFA induced MDA,ALT and AST in hepatocytes(P＜0.05),and significantly increased the levels of intracellular GSH(P＜0.05).WB results showed that esculin treatment could significantly reduce the protein expression levels of Caspase-3 and Bax(P＜0.01).The results of Nile red staining and TG content detection confirmed that esculin treatment could significantly reduce the accumulation of intracellular lipid droplets and TG content(P＜0.05).The results of qRT-PCR showed that the expression levels of PPARγ,FASN,Srebf1,Dgat2,Mvk and Acaca in hepatocytes were significantly decreased after esculin treatment(P＜0.05).In terms of mechanism,the phosphorylation levels of PERK,eIF2A and ATF4 in hepatocytes were significantly reduced by esculin treatment(P＜0.05).Conclusion Esculin could improve lipid accumulation in hepatocytes by regulating the PERK/eIF2A/ATF4 signalling pathway,which plays a positive role in maintaining the healthy state of hepatocytes.