The abnormal accumulation of neutrophil extracellular traps （NETs） can promote the initiation and progression of pancreatic cancer， which is considered a potential therapeutic target for this disease. The Miraculous Pivot·Inquiry About Statement （《灵枢·口问》） have recorded the concept of "defensive qi stagnation". Based on the recognition that the function of defensive qi is similar to the immune function of neutrophils， and combining traditional Chinese medicine theory with clinical practice， it is proposed that the abnormal accumulation of NETs may be a pathological product of "defensive qi stagnation"， with the spleen being the critical site of pathology. Further exploring the application strategy of cleaning spleen and restoring defensive qi method in pancreatic cancer treatment， it is proposed to employ three approaches such as dredging method to eliminate spleen stagnation and inhibit pancreatic cancer proliferation， cleaning method to remove spleen dampness and suppress the inflammatory micro-environment， and tonifying method to strengthen Weiqi and to improve the immune microenvironment， which aims to provide new insights for the clinical treatment of pancreatic cancer with traditional Chinese medicine.

OBJECTIVE: To investigate the clinical effect on functional dyspepsia differentiated as liver-stomach disharmony treated with acupoint application of Chinese herbal medicine and wax therapy on the basis of Professor TIAN Conghuo's theory, "regulating qi movement". METHODS: A total of 120 patients with functional dyspepsia of liver-stomach disharmony were randomly assigned to a combined therapy group (30 cases, 1 case dropped out), an acupoint application group (30 cases, 1 case dropped out), a wax therapy group (30 cases, 1 case dropped out) and a basic therapy group (30 cases, 2 cases dropped out). In the basic therapy group, omeprazole magnesium enteric-coated tablets were administered orally, 20 mg each time, once daily. Besides the treatment as the basic therapy group, the Chinese herbal acupoint application was used at Zhongwan (CV12) and Shenque (CV8) in the acupoint application group, and remained for 4 h in each intervention; and in the wax therapy group, wax therapy was delivered at the sites of Zhongwan (CV12) and Shenque (CV8) of the abdominal region and remained for 20 min in each intervention; and in the combined therapy group, the acupoint application was combined with wax therapy, administered once every other day or every two days, 3 times weekly. The duration of treatment was 4 weeks in the four groups. Before and after treatment, the score of main symptoms, the score of 36-item short-form health survey (SF-36) and the score of liver-stomach disharmony pattern were observed; and the clinical effect was evaluated in the four groups. RESULTS: After treatment, regarding main symptoms and liver-stomach disharmony pattern, the score of every item was lower than that before treatment in the 4 groups (P<0.01). The score for each dimension in SF-36 was higher than that before treatment in the combined therapy group and the acupoint application group (P<0.01, P<0.05). In the wax therapy group, the scores for physiological activities, bodily pain, general health, vitality, social activities and mental health in SF-36 were higher than those before treatment (P<0.01, P<0.05). In the basic therapy group, the scores for physiological performance, bodily pain, general health and mental health in SF-36 were higher than those before treatment (P<0.05, P<0.01). After treatment, in the combined therapy group, the score for gastric distension and discomforts was lower than those of the basic therapy group and the wax therapy group (P<0.01), and the scores for gastric fullness in the morning, pain in the upper abdominal region and burning sensation in the upper abdominal region, as well as the score for liver-stomach disharmony pattern were lower than those in the rest 3 groups (P<0.01, P<0.05). In the combined therapy group, the scores for physiological activities, physiological performance, and bodily pain were higher than those of the basic therapy group (P<0.01, P<0.05), the scores for physiological activities and bodily pain were higher when compared with those in the acupoint application group (P<0.01, P<0.05) and the scores for physiological activities and vitality were higher when compared with those in the wax therapy group (P<0.05). After treatment, the score for each item of main symptoms, the score for liver-stomach disharmony pattern in the acupoint application group, and the score for liver-stomach disharmony pattern in the wax therapy group were all lower in comparison with those in the basic therapy group (P<0.01, P<0.05). The total effective rates was 93.3% (28/30), 73.3% (22/30), 66.7% (20/30) and 50.0% (15/30) in the combined therapy group, the acupoint application group, the wax therapy group and the basic therapy group, respectively; and the total effective rate in the combined therapy group was superior to the other 3 groups (P<0.01); the total effective rates in the acupoint application group and the wax therapy group were higher than that in the basic therapy group (P<0.01). CONCLUSION The combination of acupoint application with Chinese herbal medicine and wax therapy, based on Professor TIAN Conghuo's theory of "regulating qi movement", can effectively treat functional dyspepsia, alleviate main symptoms and improve the quality of life in the patients.
Humans ; Acupuncture Points ; Dyspepsia/therapy* ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Adult ; Middle Aged ; Liver/drug effects* ; Combined Modality Therapy ; Stomach/drug effects* ; Young Adult ; Aged ; Waxes

Objective To investigate the effects and mechanisms of icariin on changes in fear memory in post-traumatic stress disorder(PTSD)rats.Methods Thirty male SD rats were used to construct a rat model of single prolonged stress(SPS).The model rats were randomly divided into the SPS,icariin,and icariin + K252a(tyrosine kinase receptor B inhibitor)groups(n= 10 each;another 10 normal rats were used as the control group).The icariin and icariin + K252a groups were administered 20 mg/kg icariin by gavage once per day after SPS,while the control and SPS groups were administered the same dose of normal saline.K252a cells were injected into the lateral ventricles.After 2 weeks,anxiety,depression,and fear memory disorder in rats in each group were detected by the mine experiment,ele-vated cross maze experiment,and conditional fear test.The binding activity of icariin to brain-derived neurotrophic factor(BDNF)and the BDNF and TrkB expressions in the rat amygdala were detected by immunohistochemistry.The relative expressions of BDNF and TrkB pro-teins were detected by Western blotting.The expressions of postsynaptic density protein 95(PSD95)and synaptophysin(SYN)in the rat amygdala were detected using immunofluorescence.Results Icariin showed strong binding to BDNF.Compared with the control group,the times of entering the central area and the percentage of movement distance in the central area in the SPS group and the icariin+K252a group were significantly reduced.The open arm entry(OE)and arm opening time(OT)were significantly reduced,the freezing time and defecation times were significantly increased,and the expressions of the BDNF,TrkB,PSD95,and SYN proteins were significantly reduced(P<0.05).Compared with the SPS group,the icariin group rats had significantly increased times of entering the central area and percentages of movement distance in the central area,significantly increased OE and OT,significantly reduced the time of immobilization and defecation,and significantly increased the expressions of BDNF,TrkB,PSD95,and SYN proteins(P<0.05).Conclusion Icariin effectively alleviated the fear memory impairment induced by SPS in rats.This protective effect is related to BDNF/TrkB signaling pathway activation and upregulated PSD95 and SYN expression.

Objective To investigate the clinical manifestations,pathological diagnosis,treatment meth-od and prognosis of primary gastric adenosquamous carcinoma.Methods The clinical data of 20 patients with primary gastric adenosquamous carcinoma receiving the treatment in this hospital from January 1,2013 to No-vember 30,2022 were retrospectively analyzed,and their clinicopathological characteristics and prognosis were analyzed.Results Among the 20 patients,14 cases were male and 6 cases were female,with a median age of 59(36,74)years old.Upper abdominal discomfort,pain and weight loss were the main clinical symptoms.Ser-um carbohydrate antigen 19-9(CA19-9)levels were elevated in some patients.The image examination indica-ted the gastric occupation.Among 20 cases,the tumors were most common in the lower third of the stomach(14 cases),followed by the upper third(1 case)and the middle third(5 cases).The most common tumors were in the lower one-third(14 cases)of the stomach,followed by the middle one-third(5 cases)and upper one-third(1 case).In histomorphology,the gastric tumor cells contained two components,adenocarcinoma and squamous cell carcinoma,and squamous cell carcinoma accounted for more than 25％of tumor cells.Immuno-histochemistry showed that the partial tumor cells of adenocarcinoma expressed CK8/18 and partial tumor cells of squamous cell carcinoma expressed p40.All 20 cases performed the surgical treatment.Only 6 cases survived and the others died of tumor recurrence or metastasis.The adenosquamous carcinoma proportion and Ki-67 were correlated with the prognosis in the patients with gastric adenosquamous carcinoma(P＜0.05).The survival curve constructed by the Kaplan-Meier method showed that when the proportion of squamous carcinoma was more than 35％,the prognosis of the patients was good.Conclusion Primary gastric adenosquamous carcinoma,mainly composed of adenocarcinoma,may be correlated with a higher risk of metastasis.

Objective To analyze the correlation between the prevalence of chronic non-communicable diseases (NCDs) and fall incidence among the elderly in urban and rural areas in Chongqing, and to provide evidence for targeted intervention. Methods In 2019, a questionnaire survey was conducted among the elderly aged 65 and over in four districts and counties using multistage stratified cluster random sampling. The difference of NCDs prevalence and fall incidence was compared by Chi-square test. The correlation between NCDs and fall incidence was analyzed by multivariate logistic regression. Results A total of 806 and 801 elderly people aged 65 and above in urban and rural areas，respectively, were investigated The fall incidence among the elderly in rural areas (12.98%) was higher than that in urban areas (7.94%) (χ2=10.916, P=0.001). The multivariable logistic regression analysis showed that the prevalence of heart disease (OR=2.988, 95%CI:1.544-5.785), osteoporosis (OR=2.696, 95%CI:1.527-4.760) and vestibular dysfunction or deafness (OR=3.180, 95%CI:1.142-8.861) was associated with fall incidence among urban elderly people. Factors including need for care (OR=2.315，95%CI：1.130-4.744), diabetes (OR=3.067，95%CI:1.634-5.756), osteoporosis (OR=1.972, 95%CI:1.210-3.214), and arthritis (OR=2.975, 95%CI:1.901-4.657) were associated with fall incidence among rural elderly people. Conclusion The fall incidence among the elderly in rural areas is higher than that in urban areas in Chongqing. The prevalence of NCD is high among the elderly. Timely treatment of NCDs should be provided to reduce fall incidence among the elderly.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Objective:To study the risk factors of complications after bowel resection for acute mesenteric ischemic disease.Methods:Retrospective case-control study was used to analyze the case data of 68 patients diagnosed with acute mesenteric ischemic disease (AMI) with bowel resection at the First Medical Center of the PLA General Hospital from January 2010 to January 2020, including 43 males and 25 females. The patients were divided into complication group ( n=21) and the non-complication group ( n=47) according to whether they had complications after surgery. The risk factors associated with the development of postoperative complications were analyzed by multivariate Logistic stepwise regression method to determine the risk factors with clinical significance. Measurement data with normal distribution were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups. Chi-square test was used for comparison between count data groups. Results:Univariate analysis showed that age >60 years, Marshall score≥2, type of resected bowel, pathology suggestive of irreversible transmural necrosis, length of ICU stay >6 d, length of mechanical ventilation >2 d, American Society of Anesthesiologists (ASA) classification, and preoperative procalcitonin≥2 ng/mL were the risk factors affecting the development of complications after bowel resection for acute mesenteric ischemic disease risk factors ( P<0.05). Multivariate Logistic regression analysis showed that age>60 years ( HR=12.364, 95% CI: 1.135-134.662, P=0.039) and preoperative procalcitonin ≥2 ng/mL ( HR=14.144, 95% CI: 1.280-156.303, P=0.031) were independent risk factors for the development of postoperative complications after AMI parallel bowel resection. Conclusion:The rate of complications after combined bowel resection for AMI is high. When patients are combined with age>60 years and preoperative procalcitonin≥2 ng/mL, preoperative prevention of postoperative complications should be emphasized to improve the prognosis of patients.

Objective : To investigate the role of hepatic long-chain non-coding RNA (lncRNA) H19 in key genes associated with glucose metabolism disorder induced by p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE). Methods: Human embryonic liver CCC-HEL-1 cells were divided into the DMSO group, 0.1 μmol/L p,p′-DDE group, 1 μmol/L p,p′-DDE group, 10 μmol/L p,p′-DDE group, small interference RNA (siRNA)+DMSO group and siRNA+10 μmol/L p,p′-DDE group. The promoter region methylation, mRNA expression and protein expression of hepatocyte nuclear factor 4α (HNF4α), forkhead box transcription factor O1 (FoxO1) and insulin-like growth factor (IGF2) were detected in CCC-HEL-1 cells using the bisulfite method, real-time fluorescence quantitative PCR (qPCR) assay and BCA assay, respectively. The changes in H19 mRNA expression, the methylation of associated genes in the promoter region and transcriptional expression were compared in CCC-HEL-1 among groups. Results: Exposure to p,p′-DDE alone at different doses resulted in an increase in H19 expression, and the H19 mRNA expression was higher in the 10 μmol/L p,p′-DDE group than in the DMSO group [(1.31±0.25) vs. (1.02±0.22); P<0.05]. Lower methylation of the HNF4α gene in the pro moter region [(38.59±32.77)% vs. (61.43±24.64)%; P<0.05] and higher HNF4α mRNA expression [(1.33±0.26) vs. (1.03±0.28); P<0.05] were detected in the 10 μmol/L p,p′-DDE group than in the DMSO group, while no significant differences were detected between the two groups in terms of the methylation of FoxO1 and IGF2 genes in the promoter region, FoxO1 and IGF2 mRNA and protein expression (P>0.05). Following siRNA-induced H19 knockdown, higher methylation of the HNF4α gene in the promoter region [(71.33±22.23)% vs. (38.59±32.78)%; P<0.05], lower HNF4α mRNA expression [(0.71±0.17) vs. (1.33±0.26); P<0.05], higher methylation of FoxO1 gene in the promoter region [(47.73±34.24)% vs. (25.09±25.35)%; P<0.05] and higher IGF2 mRNA [(1.39±0.25) vs. (0.80±0.20); P<0.05] were found in the siRNA+DMSO group than in the 10 μmol/L p,p′-DDE group, and higher IGF2 protein expression was detected in the siRNA+DMSO group than in the DMSO group [(1.03±0.11) vs. (0.74±0.12); P<0.05]. Conclusion Hepatic H19 may alter HNF4α, FoxO1 and IGF2 transcription and expression through mediating the methylation of genes in the promoter region, thereby playing a role in p,p′-DDE-induced glucose metabolism disorders.

Chemically defined medium is widely used for culturing mouse embryonic stem cells (mESCs), in which N2B27 works as a substitution for serum, and GSK3β and MEK inhibitors (2i) help to promote ground-state pluripotency. However, recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs. Here, we demonstrated the deficient bone morphogenetic protein (BMP) signal in the chemically defined condition is one of the main causes for the impaired pluripotency. Mechanistically, activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream targets Ube2s and Chmp4b. More importantly, BMP4 promotes a distinct in vivo developmental potential and a long-term pluripotency preservation. Besides, the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression. Taken together, our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
Animals ; Bone Morphogenetic Protein 4/metabolism* ; Cell Differentiation ; Chromosomal Instability ; Endosomal Sorting Complexes Required for Transport ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Mouse Embryonic Stem Cells/cytology* ; Pluripotent Stem Cells/cytology* ; Signal Transduction ; Ubiquitin-Conjugating Enzymes