Objective: To investigate the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF) on histone H3 lysine 18 lactylation (H3K18la) in the hippocampus of rats with diabetes mellitus complicated with depression (DD) and predict the regulatory genes of H3K18la. Methods: Male Sprague-Dawley rats were divided into control, model, and positive drug (metformin [0.18 g/kg] and fluoxetine [1.8 mg/kg]) groups, and the three groups were treated with high, medium, and low ZGJTJYF doses (20.52, 10.26, and 5.13 g/kg, respectively), with 10 rats per group. After treatment, the forced swimming and water maze tests were performed to assess depressive-like behaviors and cognitive function. An enzyme-linked immunosorbent assay was used to measure blood insulin, glycosylated hemoglobin, lactate levels, and lactate content in the hippocampus. Western blotting was used to detect H3K18la expression in the hippocampus. Cleavage Under Targets and lagmentation(CUT&Tag) experiments targeted hippocampal H3K18la epigenetic modification regions to analyze the transcription factors bound by H3K18la. Kyoto Encyclopedia of Genes and Genomes and Protein-Protein Interaction networks were constructed to identify key pathways and target genes regulated by H3K18la. Results: Compared with the normal group, the model group rats showed prolonged immobility time in the forced swim test, increased escape latency in the water maze experiment, decreased target quadrant distance ratio (P<0.01), increased serum lactate content, and decreased lactate content in hippocampal homogenate (P<0.01), as well as decreased H3K18la protein expression in the hippocampus (P<0.01). Compared with the model group, ZGJTJYF reduced the immobility time in the forced swim test and the escape latency in the water maze test (P<0.01), while the distance ratio in the target quadrant increased (P<0.01) in model rats. Lowered fasting blood glucose, insulin, and glycosylated hemoglobin levels (P<0.05, P<0.01) were also observed. ZGJTJYF also increased the lactate content and H3K18la protein expression in hippocampal homogenate (P<0.05, P<0.01). The DNA sequences bound by H3K18la were predominantly enriched at the transcription start sites. ZGJTJYF modulated H3K18la-associated pathways, including cell adhesion junctions, tumor growth factor-beta (TGF-β) signaling, stem cell pluripotency regulation, mitogen-activated protein kinase(MAPK) signaling pathway, and insulin resistance, leading to the identification of 12 target genes. Conclusion ZGJTJYF enhances hippocampal lactate levels and H3K18la modification in DD rats, which may regulate neural cell interactions, neurogenic stem cell function, TGF-β signaling, MAPK signaling, and insulin resistance pathways.

Lung cancer is the leading cause of cancer-related deaths worldwide,with metastasis being the primary cause of mortality in lung cancer patients,and its prevention and control efficacy remain limited.In recent years,immunothera-py has emerged as a promising direction for overcoming the bottleneck of metastasis.Macrophages,as essential components of innate immunity,participate in the entire process of tumor initiation and progression.Tumor-associated macrophages(TAMs)represent the most abundant immune population in the tumor microenvironment(TME),displaying both anti-tumor M1-like and pro-tumor M2-like phenotypes.The latter promotes tumor invasion and metastasis,angiogenesis,lymphangiogenesis,immune suppression,and reactivation of dormant disseminated tumor cells(DTCs),thereby facilitating tumor metastasis.In recent years,traditional Chinese medicine(TCM)has shown significant efficacy in inhibiting tumor metastasis and has been extensively validated.It exerts anti-tumor effects by reducing the recruitment of TAMs,inhibiting M2-like polarization,and modulating cytokines and proteins in the TME.This paper reviews the relationship between TAMs and lung cancer metastasis,elucidates the targets and mechanisms of TCM in regulating TAMs to prevent and treat lung cancer metastasis,aiming to pro-vide insights into lung cancer prevention and treatment.

ObjectiveTo explore and verify the key pathway of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression by means of gene set enrichment analysis （GSEA） and short time-series expression miner （STEM）. MethodSD rats were randomly divided into six groups， including a normal group， a model group， high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription， and a positive drug group. The model of diabetes with depression was established by high-fat feeding， streptozotocin （STZ） injection， and chronic mild unpredictable stress. The high， medium， and low dose groups of Zuogui Jiangtang Jieyu prescription were orally administered at 20.52， 10.26， and 5.13 g·kg^-1 respectively. The positive drug group was orally administered 0.18 g·kg^-1 metformin and 1.8 g·kg^-1 fluoxetine. The rats in the normal group and model group were administered with an equal volume of distilled water. After 28 days， the animals were tested for depressive-like behaviors and cognitive function using the forced swimming test and Morris water maze. Fasting blood glucose was measured using blood glucose test strips. Cholesterol and triglyceride levels were measured using enzyme-linked immunosorbent assay （ELISA）. Three hippocampus samples were randomly selected from the normal group， the model group， the high dose group of Zuogui Jiangtang Jieyu prescription for high-throughput transcriptome sequencing. Differential gene analysis， GSEA analysis， and STEM analysis were used to screen the key pathways and target genes of Zuogui Jiangtang Jieyu prescription in the treatment of diabetes with depression. Key target genes were validated using real-time fluorescence quantitative PCR （Real-time PCR）. The expression of the signal protein mediated by the target genes was detected by Western blot. ResultCompared with the results in the normal group， the fasting blood glucose， cholesterol， and triglyceride levels in the model group were significantly increased （P<0.01）. Moreover， the immobility time in the forced swimming test was significantly increased， while the time to climb the platform was significantly prolonged， and the search distance in the target quadrant was significantly reduced in the Morris water maze test （P<0.05，P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly reduced the levels of blood glucose， cholesterol， and triglycerides in rats with diabetes with depression （P<0.05，P<0.01）， reduced the immobility time in the forced swimming test， shortened the stage time in the Morris water maze test， and increased the search distance ratio in the target area （P<0.05，P<0.01）. Transcriptome sequencing differential analysis showed that the normal group had 1 366 differentially expressed genes compared to the model group， while the model group had 1 149 differentially expressed genes compared to the high dose group of Zuogui Jiangtang Jieyu prescription， with 581 intersecting genes. The GSEA results showed that there were 9 sets of differentially expressed genes between the normal group and the model group， and 43 sets of differentially expressed genes between the model group and the high dose group of Zuogui Jiangtang Jieyu prescription， with 7 intersecting gene sets. STEM analysis showed that according to the analysis order of the normal group， model group， and high dose group of Zuogui Jiangtang Jieyu prescription， two significantly different trend clustering groups were obtained. One key gene set for axonal guidance， as well as key target signal elements Sema3c， Sema7a， Robo3， Epha8， and Epha7， were identified through synthesizing the three analysis results. Real-time PCR validated that compared with the results in the normal group， the mRNA expression of Robo3， Sema7a， and Epha7 in the hippocampus of the model rats was significantly reduced （P<0.05， P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the mRNA expression of Robo3， Sema7a， and Epha7 （P<0.05， P<0.01）. Western blot results showed that compared with the results in the normal group， the Sema7a， ITGB1， and FAK protein expression in the hippocampus of the model group was significantly reduced （P<0.01）. Compared with the model group， the high dose of Zuogui Jiangtang Jieyu prescription significantly increased the protein expression of Sema7a， ITGB1， and FAK in the hippocampus （P<0.05，P<0.01）. ConclusionZuogui Jiangtang Jieyu prescription may treat diabetes with depression by regulating axonal guidance based on the Sema7a/ITGB1 signaling pathway.

OBJECTIVE: To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression. METHODS: Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (n=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting. RESULTS: The diabetic rats with depression showed significantly increased levels of blood glucose and leptin (P < 0.01) and prolonged immobility time in forced swimming test (P < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test (P < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased (P < 0.01) while hippocampal Gli-3 expression was increased significantly (P < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose (P < 0.01) and leptin level (P < 0.05) and improved their performance in behavioral tests (P < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus (P < 0.01) and reduced hippocampal expression of Gli-3 (P < 0.05) in the rat models. CONCLUSION ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.
Animals ; Rats ; Blood Glucose ; Bromodeoxyuridine ; Cell Self Renewal ; Cyclin D1 ; Dentate Gyrus ; Depression ; Diabetes Mellitus, Experimental ; Hippocampus ; Leptin ; Nestin ; Rats, Sprague-Dawley

Objective:To explore the clinical efficacy of kidney transplantation(KT)from senile living-related donors aged over 70 years.Methods:Between 2017 and 2019, perioperative and follow-up data from 18 pairs of donors and recipients were retrospectively reviewed.Results:Operations of all 18 pairs of recipients and donors were conducted successfully without serious perioperative complications.No delayed graft function occurred.There was 1 episode(5.6%)of acute rejection.The mean level of serum creatinine(SCr)at Day 3 post-KT and at discharge was(155.7±63.5)and(97.6±28.7)μmol/L.The median follow-up period was 37.5 months.All 18 donors survived with normal renal function.And no proteinuria or kidney donation related hospitalization events occurred.SCr was(84.4±15.0)μmol/L at the last follow-up and there was no statistical significance as compared with SCr level at discharge( P=0.610). No recipient mortality or graft loss occurred.Levels of SCr were(92.1±18.3), (95.5±21.9)and(100.1±21.2)μmol/L at Month 12/24 and the last follow-up.No statistical difference existed in posttransplant SCr level at these follow-up timepoints( P=0.507). Posttransplant proteinuria occurred in 3 recipients(16.7%). In 8 donors, donated kidney glomerular filtration rate(GFR)was lower than 40 ml/(min·1.73m 2). No statistical difference existed in posttransplant SCr level between this group and higher GFR group( P>0.05). Conclusions:After thorough preoperative assessments, satisfactory short-term outcomes may be achieved for KT from living-related donors aged over 70 years.The long-term outcome should be further explored.

Objective:To investigate the effects of microskin transplantation with antigen-free porcine peritoneum (AFPP) as substitutive carrier for allogeneic skin graft in treating patients with extensive deep burns.Methods:Medical records of 32 patients with extensive deep burns, hospitalized in Changhai Hospital of Naval Medical University meeting the inclusion criteria were investigated from January 2014 to December 2017. Twenty patients [12 males and 8 females, aged (35.4±2.2) years]with microskin transplantation using allogeneic skin graft as microskin carrier were included in allogeneic skin graft group and 12 patients [6 males and 6 females, aged (32.1±4.8) years] with microskin transplantation using AFPP as microskin carrier were included in AFPP group. On post injury day 3-7, the vital signs of patients were stable and escharectomy and autologous microskin grafting of head were performed. The expansion ratio of microskin, the application time of albumin and antibiotics, the percentage of infectious autologous microskin grafting area, the survival rate of microskin, and dressing change times of patients in 2 groups were recorded. Data were statistically analyzed with t test. Results:The expansion ratio of microskin of patient in AFPP group was 14.8±0.6, which was close to 13.5±0.6 of allogeneic skin graft group ( t=1.531, P>0.05). The application time of albumin and antibiotics of patients in AFPP group were close to those of allogeneic skin graft group ( t=0.027, 1.121, P>0.05). The percentage of infectious autologous microskin grafting area of patients in AFPP group was (8.5±1.2)%, which was significantly lower than (18.1±0.6)% in allogeneic skin graft group in 4 weeks after surgery( t=7.593, P<0.01), the survival rate of microskin of patients in AFPP group was (82.5±1.1)%, which was significantly higher than (72.5±0.6)% in allogeneic skin graft group ( t=8.689, P<0.01). The dressing change time of patients in AFPP group was significantly less than that in allogeneic skin graft group ( t=4.743, P<0.01). Conclusions:Compared with allogeneic skin graft, microskin transplantation with AFPP as carrier can reduce wound infection, improve the survival rate of microskin graft, and reduce dressing change time, so that AFPP is a good carrier of microskin.

Objective To investigate the management and clinical effect of accessory renal artery in living-related donor renal transplantation. Methods Clinical data of 277 donors and recipients undergoing living-related donor renal transplantation were retrospectively analyzed. According to the results of preoperative CT angiography (CTA), the donor kidney was selected and the accessory renal artery of the renal graft was treated intraoperatively. Intraoperative status of the donors, and intraoperative management, postoperative complications, clinical prognosis of the recipients were summarized. Results Among 277 cases of renal transplantation, accessory renal arteries were detected in 83 donors by preoperative CTA examination with an accuracy rate of 95%. Fifty-eight donor kidneys with accessory renal arteries were obtained. Twenty-five donor kidneys with accessory renal arteries were reconstructed and anastomized by vascular repairing. Among them, 1 patient presented with anastomotic thrombosis during abdominal closure, whereas the other 24 cases were successfully anastomized with excellent blood flow. No complications, such as hemorrhage, renal graft embolism, ureteral necrosis and urinary fistula, occurred after renal transplantation. The 1-year survival rates of the recipients and renal grafts were 94% and 91%. The clinical efficacy did not significantly differ between the recipients with single renal artery and their counterparts with accessory renal artery (P > 0.05). Conclusions It can be obtained good clinical efficacy of renal transplantation by selecting a suitable donor kidney and reconstructing and anastomizing the accessory renal artery of the renal graft through vascular repair.

Objective To investigate the clinical efficacy of multi-functional fire needling plus auricular plaster therapy for moderate to severe acne vulgaris.Methods One hundred and fifty patients with moderate to severe acne vulgaris were randomly allocated to treatment and control groups, 75 cases each. Both groups were first given bloodletting at Ear apex and Helix 4. Then the treatment group received multi-functional fire needling plus auricular plaster therapy and the control group, auricular plaster therapy alone. The symptom and sign score was recorded in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups.Results There was a statistically significant pre-/post-treatment difference in the symptom and sign score in the two groups (P<0.01). There was a statistically significant post-treatment difference in the symptom and sign score between the two groups (P<0.05). The total efficacy rate and the cure and marked efficacy rate were 98.6% and 88.7%, respectively, in the treatment group and 93.2% and 60.8%, respectively, in the control group. There was a statistically significant difference in the cure and marked efficacy rate between the two groups (P<0.05).Conclusion Multi-functional fire needling plus auricular plaster therapy is an effective way to treat moderate to severe acne vulgaris.

Objective To analyze and compare the pathological changes of lung tissue in mice infected with the novel H7N9 influenza virus and 2009 pandemic H1N1 influenza virus, respectively, and to preliminarily study the mecha-nisms of acute lung injury induced by those virus infection .Methods SPF 6-week old BALB/c mice ( body weight 18-20 g, male∶female=1∶1) (n=3 in each subgroup) were intranasally infected with H7N9 virus and H1N1 virus, respec-tively.The behavior and survival time of mice after virus infection were observed and the survival rates were analyzed .The heart, liver, spleen, lung, kidney, intestines, and brain were collected at indicated time points for histopathological exami-nation using H&E staining .The distribution of virus antigen was detected by immunohistochemistry .The neutrophil infiltra-tion was also observed .The correlation of lung injury with virus replication and host immune responses was analyzed .Re-sults The lung and spleen injury of mice infected with H 7N9 virus was slighter and their survival rate (100%) was high-er than those of mice infected with H1N1 virus.The damages of the lung and spleen in H1N1virus-infected mice were more severe than that in H7N9 virus-infected mice, and all the 10 mice in this group died within 9 days after virus inoculation . The distributions of both the virus antigens were mainly in the bronchial epithelial cells , a few stromal cells and alveolar ep-ithelial cells .The levels of virus replication in the two groups were not significantly different .There were more intense neu-trophil infiltration in the lung and inflammatory response in the H 1N1 virus-infected mice than those in the H7N9 virus-in-fected mice .Conclusions There are some differences of the pathological characteristics and extent of lung injury in the mice infected with H7N9 virus and H1N1 virus, respectively.The virus replication is a precipitating factor but not the deci-sive factor of the lung injury , and there is a close relationship between the host immune responses and acute lung injury .

Objective To survey the current status of community pharmacy care, analyze the needs of both community residents and medical staff for community pharmacy care, and provide references for improving the quality of communi-ty pharmacy care and policy making. Methods The form of questionnaire was taken for community residents and com-munity pharmacists from community health service centers, a random survey was conducted to collect information for statistical analysis. Results Sixty-six point eight percent of community residents selected community health service center as the main choice for obtaining drugs. The residents' home-stored drugs were mainly for cold/fever, abdominal pain/diarrhea, common chronic diseases, external wounds treating and antibacterial. Only 16.8%of community residents stored the drugs according to instructions, 70.6% would use antibacterial drug by themselves under various circum-stances, 82.8% thought there were errors in drug usage, over 98.0% of community pharmacists recognized the impor-tance of pharmaceutical care and the needs for further development. 89.1% of them were eager to improve their own capability of serving and have the needs of collaboration with large hospitals. Conclusion Improper drug usage and storage are common among community residents. Their expectations for pharmaceutical service are increasing. And community pharmacists expected to improve their own pharmacy service capability.