Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Atoh1 gene encodes a helix-loop-helix transcription factor which is involved in the generation and differentiation of mammalian auditory hair cells and supporting cells, and regulation of the proliferation of cochlear cells, therefore plays an important role in the pathogenesis and recovery of sensorineural deafness. This study reviews the progress of the Atoh1 gene in hair cell regeneration, with the aim of providing a reference for the study of hair cell regeneration gene therapy for sensorineural deafness.
Animals ; Humans ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Hair Cells, Auditory/physiology* ; Transcription Factors ; Hearing Loss, Sensorineural ; Cell Differentiation ; Deafness ; Regeneration/genetics* ; Mammals

Objective:To investigate the application value of carbon nanoparticle tracer in lymph node dissection for Siewert type Ⅱ and Ⅲ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 147 patients with Siewert type Ⅱ and Ⅲ AEG who were admitted to Shengli Petroleum Central Hospital from June 2015 to July 2020 were collected. There were 109 males and 38 females, aged (65±9)years. All the patients underwent laparoscopic-assisted radical resection of AEG via esophageal hiatus. Of 147 patients, 61 cases not injected with carbon nanoparticle tracer preoperatively were allocated into control group and 86 cases injected with carbon nanoparticle tracer preoperatively were allocated into experimental group. Observation indicators: (1) surgical and postoperative situations; (2) influencing factors analysis of No.10 lymph nodes metastasis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. Univariate analysis was conducted by statistic methods based on data type, and multivariate analysis was conducted by the Logistic step-wise regression model. Results:(1) Surgical and postoperative situations. Patients of the experimental group and control group completed laparoscopic-assisted radical resection of AEG via esophageal hiatus successfully. There was no significant difference in the operation time, volume of intraoperative blood loss, the total number of lymph node dissection, the number of the first station, the second station and positive lymph nodes between the two groups ( P>0.05). For the experimental group, the black staining rate of lymph nodes was 57.937%(1 365/2 356), the black staining rate of the first station and second station lymph nodes was 77.989%(1 024/1 313) and 43.691%(232/531), the black staining rate of Siewert type Ⅱ and Ⅲ AEG patients was 56.855%(423/744) and 58.437%(942/1 612), respectively. The lymph node metastasis rate was 19.091%(815/4 269) of 147 patients, 18.573%(242/1 303)of Siewert type Ⅱ AEG patients and 19.319%(573/2 966) of Siewert type Ⅲ AEG patients. For Siewert type Ⅱ AEG patients, the metastasis rate of No.1, 2, 3, 4sa, 4sb, 7, 8a, 11p lymph nodes was more than 10%, the metastasis rate of No.4d, 5, 6, 9, 10, 11d, 12a lymph nodes was lower than 10%. For Siewert type Ⅲ AEG patients, the metastasis rate of No.1, 2, 3, 4sa, 4sb, 7, 8a, 10, 11p and lower mediastinal lymph nodes was more than 10%, the metastasis rate of No.4d, 5, 6, 9 11d, 12a and lower mediastinal lymph nodes was lower than 10%. There was no significant difference in the Clavien Dindo classification of postoperative complications between the two groups ( P>0.05). (2) Influencing factors analysis of No.10 lymph nodes metastasis. Results of multivariate analysis showed that tumor T staging and degree of tumor differention was an independent influencing factor for No.10 lymph nodes metastasis ( P<0.05). Conclusions:For Siewert type Ⅱ and Ⅲ AEG patients, the application of carbon nano-partide tracer can not increase the number of lymph node dissection. The second station lymph node dissection should be paid attention for Siewert type Ⅱ AEG. Tumor T staging and degree of tumor differentiation are independent influencing factors for No.10 lymph nodes metastasis.

Objective:To evaluate the usability of gamification coronary heart disease health management platform based on WeChat, so as to provide support for self-management of coronary heart disease patients.Methods:From November to December 2022, 10 patients with coronary heart disease who were treated at Dongzhimen Hospital of Beijing University of Chinese Medicine were selected using convenience sampling. The research subjects registered for the health management platform by scanning the QR code and underwent a 2-month trial experience. Two months later, researchers collected data from the platform and used a combination of questionnaire surveys and qualitative interviews to investigate the user's experience and feedback of the research subjects, in order to evaluate the usability of the platform.Results:Within two months, the health management platform had 226 visits, an average visit time of 26 minutes, and an availability questionnaire score of (71.8±2.8). The research subjects had an acceptable attitude towards the usability of this platform, had a good overall user experience, and had also provided improvement suggestions for the platform while they gained beneficial experiences.Conclusions:The gamification coronary heart disease health management platform based on WeChat has good usability, providing a feasible means for the health management of heart disease patients, and also providing reference for other chronic disease health management projects involving lifestyle changes and incentives.

Objective:To evaluate the independent prognostic value of minute ventilation/carbon dioxide production slope (VE/Vco 2 slope)on heart failure after acute myocardial infarction. Methods:131 patients with acute myocardial infarction (AMI) treated in the cardiology department of China-Japan Friendship Hospital from September 2018 to September 2019 were collected and followed up 3 months after discharge. They were divided into heart failure (HF) group and non-heart failure (NHF) group. All the patients underwent cardiopulmonary exercise test (CPET) before discharge.Results:Three months after discharge, the VE/Vco 2 slope was higher in HF group than in NHF group (36.7±3.8 vs 29.7±4.0, P=0.014). The best VE/Vco 2 slope cutoff for the prediction of heart failure after 3 month was 33.05 with a sensitivity of 81.4% and a specificity of 80.6% [area under curve (AUC) was 0.844, P<0.001]. VE /Vco 2 slope level was an independent predictor of heart failure in patients with acute myocardial infarction after discharge ( OR=1.245, 95% CI: 1.021-1.366, P=0.019). Other independent indicators related to heart failure included N-terminal pro-B type natriuretic peptid (NT-proBNP) level ( OR=1.283, 95% CI: 1.019-1.399, P=0.033). Conclusions:VE/Vco 2 slope yielded strong, independent predictive value for heart failure at 3 month after discharge to AMI patients.

Objective:To investigate the effect of hourly ambient temperature exposure on emergency calls in Xuchang city and Zhengzhou city.Methods:The hourly meteorological data, air pollution data and emergency calls of Xuchang city and Zhengzhou city were collected from January 1, 2017 to October 31, 2019. A distributed lag non-linear model was used to calculate the excess relative risk ( ERR). The lag effect and cumulative effect of extreme temperature exposure on emergency calls were evaluated. Results:The relationship between hourly temperature exposure and emergency calls was a U-shaped curve. In Xuchang city and Zhengzhou city, both low and high temperatures would increase the number of hourly emergency calls. The earliest effect of low temperature occurred at a lag of 22 h and 52 h, with ERR values (95% CI) about 0.20% (0.00%, 0.39%) and 0.11% (0.00%, 0.22%), respectively. The earliest effect of high temperature occurred at a lag of 0 h with ERR values about 1.59% (1.09%, 2.09%) and 1.45% (1.22%, 1.69%), respectively. High temperature had the greatest impact on the number of emergency calls of cardiovascular disease at a lag of 4-8 h. The cumulative ERR values (95% CI) of the two cities were 8.70% (4.98%, 12.75%) and 3.89% (2.61%, 5.22%), respectively. Conclusion:High temperature exposure could increase the number of emergency calls within a few hours, while the effect of low temperature would not occur until 22 hours later.

Objective:To investigate the effect of hourly ambient temperature exposure on emergency calls in Xuchang city and Zhengzhou city.Methods:The hourly meteorological data, air pollution data and emergency calls of Xuchang city and Zhengzhou city were collected from January 1, 2017 to October 31, 2019. A distributed lag non-linear model was used to calculate the excess relative risk ( ERR). The lag effect and cumulative effect of extreme temperature exposure on emergency calls were evaluated. Results:The relationship between hourly temperature exposure and emergency calls was a U-shaped curve. In Xuchang city and Zhengzhou city, both low and high temperatures would increase the number of hourly emergency calls. The earliest effect of low temperature occurred at a lag of 22 h and 52 h, with ERR values (95% CI) about 0.20% (0.00%, 0.39%) and 0.11% (0.00%, 0.22%), respectively. The earliest effect of high temperature occurred at a lag of 0 h with ERR values about 1.59% (1.09%, 2.09%) and 1.45% (1.22%, 1.69%), respectively. High temperature had the greatest impact on the number of emergency calls of cardiovascular disease at a lag of 4-8 h. The cumulative ERR values (95% CI) of the two cities were 8.70% (4.98%, 12.75%) and 3.89% (2.61%, 5.22%), respectively. Conclusion:High temperature exposure could increase the number of emergency calls within a few hours, while the effect of low temperature would not occur until 22 hours later.

The development of gastritis is associated with an increased risk of gastric cancer. Current invasive gastritis diagnostic methods are not suitable for monitoring progress. In this work based on 78 gastritis patients and 50 healthy individuals, we observed that the variation of tongue-coating microbiota was associated with the occurrence and development of gastritis. Twenty-one microbial species were identified for differentiating tongue-coating microbiomes of gastritis and healthy individuals. Pathways such as microbial metabolism in diverse environments, biosynthesis of antibiotics and bacterial chemotaxis were up-regulated in gastritis patients. The abundance of Campylobacter concisus was found associated with the gastric precancerous cascade. Furthermore, Campylobacter concisus could be detected in tongue coating and gastric fluid in a validation cohort containing 38 gastritis patients. These observations provided biological evidence of tongue diagnosis in traditional Chinese medicine, and indicated that tongue-coating microbiome could be a potential non-invasive biomarker, which might be suitable for long-term monitoring of gastritis.

Objective To evaluate the relationship between the mechanism underlying inhibition of inflammatory responses induced by α7 nicotinic acetylcholine receptor(α7nAChR)agonist postcondition?ing alone or in combination with remote limb ischemic postconditioning during myocardial ischemia?reperfu?sion(I∕R)and glycogen synthase kinase?3β(GSK?3β)in rats. Methods Eighty adult male Sprague?Dawley rats, aged 8 weeks, weighing 290-320 g, were divided into 4 groups(n=20 each)using a ran?dom number table: I∕R group, α7nAChR agonist postconditioning group(group P), remote limb ische?mic postconditioning group(group L)and α7nAChR agonist postconditioning plus remote limb ischemic postconditioning group(group P+L). Myocardial I∕R was induced by 30 min occlusion of the left anterior descending branch of coronary artery followed by 120 min reperfusion. Specific α7nAChR agonist PNU282987 2 mg∕kg was intravenously injected immediately before reperfusion in group P. In group L, limb ischemia was induced by tourniquet occlusion of bilateral hind paws for 10 min starting from 20 min of myocardial ischemia, and the tourniquet was released at the beginning of reperfusion. Combination of inter?vention measures previously described in P and L groups was performed in group P+L. Venous blood sam?ples were taken at 120 min of reperfusion for determination of serum troponin I(TnI)and creatine kinase?MB(CK?MB)concentrations, myocardial infarct size(IS)and expression of phosphorylated GSK?3β [p?GSK?3β(Ser536)], NF?κBp65 and phosphorylated nuclear factor?κBp65(p?NF?κBp65)in myocar?dial tissues(by Western blot). Results Compared with group I∕R, myocardial IS and serum cTnI and CK?MB concentrations were significantly decreased, the expression of p?GSK?3β(Ser9)in ischemic area was up?regulated, and the expression of p?NF?κBp65 in ischemic area was down?regulated in P, L and P+L groups(P<0.05). Compared with group L, myocardial IS and serum cTnI and CK?MB concentrations were significantly decreased, the expression of p?GSK?3β(Ser9)in ischemic area was up?regulated, and the expression of p?NF?κBp65 in ischemic area was down?regulated in group P+L(P<0.05). Conclusion The mechanism by which α7nAChR agonist postconditioning alone or in combination with remote limb is?chemic postconditioning inhibits inflammatory responses during myocardial I∕R may be related to inhibiting GSK?3β activity in rats.

Objective To evaluate the role of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)or Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT-3)signaling pathways in reduction of myocardial ischemia-reperfusion(I/R)injury by combination of limb ischemic and morphine postconditioning in rats.Methods Eighty SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 280-320 g,were used in the study.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.The rats were divided into 8 groups(n=10 each)using a random number table:I/R group,limb ischemic postconditioning group(LIP group),morphine postconditioning group(group MP),combination of limb ischemic and morphine postconditioning group(LIP+MP group)and signaling pathway blocker groups(I/Rb group,LIPb group,MPb group,LIP+MPb group).In I/R,LIP,MP and LIP+MP groups,the animals were sacrificed at the end of reperfusion,and myocardial specimens in ischemic and non-ischemic regions were obtained for determination of phosphorylated STAT-3(p-STAT-3),STAT-3,phosphorylated Akt(p-Akt)and Akt expression(by Western blot)and STAT-3 and Akt mRNA expression(by polymerase chain reaction).In I/Rb,LIPb,MPb and LIP+MPb groups,PI3K/Akt signaling pathway blocker LY294002 0.3 mg/kg was intravenously injected in 5 rats of each group,and JAK/STAT-3 signaling pathway blocker AG490 5 mg/kg was intravenously injected in the other 5 rats of each group.The animals were sacrificed at the end of reperfusion,and myocardial specimens in the ischemic region were obtained for determination of myocardial infarct size.Results Compared with I/R group,the p-STAT-3/STAT-3 ratio in LIP,MP and LIP+MP groups and p-Akt/Akt ratio in LIP+MP group were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).Compared with LIP and MP groups,the p-STAT-3/STAT-3 and p-Akt/Akt ratios were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).There was no significant difference in myocardial infarct size between the four groups when PI3K inhibitor LY294002 was applied(P>0.05).When JAK2 inhibitor AG490 was applied,the myocardial infarct size was significantly smaller in LIP+MPb group than in I/Rb,LIPb and MPb groups(P<0.05),and there was no significant difference in myocardial infarct size between I/Rb,LIPb and MPb groups(P>0.05).Conclusion Combination of limb ischemic and morphine postconditioning can enhance the activation of PI3K/Akt or JAK/STAT-3 signaling pathways,and the cardioprotection is dependent on the integrity of the PI3K/Akt signaling pathway and partially dependent on the integrity of the JAK/STAT-3 signaling pathway when applied in combination in rats.