The culture of suspended Vero cells is facing difficulties such as low cell viability and long doubling time. To investigate the main reasons for the slow growth and low viability of suspended Vero cells, this study conducted transcriptomic analysis of suspended Vero cells (Vero-XF) and adherent Vero cells (Vero-AD) to screen the differentially expressed genes (DEGs) affecting the growth of suspended cells. In addition, epidermal growth factor (EGF) was supplemented to the culture system to improve the growth of Vero-XF. The results showed that compared with the Vero-AD group, the Vero-XF group had 7 376 significant DEGs. Kyoto encyclopedia of genes and genomes enrichment analysis revealed that the DEGs were mainly enriched in the autophagy and mitophagy pathways. Eleven DEGs were selected and verified by quantitative real-time PCR, which showed up-regulated expression of ATG9B, WIPI2, LAMP2, OPTN, Rab7a, and DEPTOR and down-regulated expression of ATG4D, being consistent with the results of transcriptomic analysis. In addition, the Vero-XF group showed significantly up-regulated expression of ATG101, ATG2A, and STX17 and insignificant change in the expression of NBR1, compared with the Vero-AD group. The protein levels of LC3 and P62 in Vero-XF and Vero-AD were determined by Western blotting, which showed up-regulated expression of LC3Ⅱ/Ⅰ and down-regulated expression of P62 in Vero-XF, indicating a higher level of autophagy. Finally, the exogenous supplementation of EGF at 10, 20, and 30 μg/L in the culture system reduced the autophagy level of Vero-XF by 22.35%, 48.15%, and 71.29%, increased the specific growth rate by 15.48%, 33.33%, and 57.14%, and decreased the apoptosis rate by 2.84%, 15.46%, and 16.23%, respectively. The results of this study preliminarily reveal that the activation of autophagy is one of the reasons for the slow growth of Vero-XF, which provides reference for the subsequent culture of suspended Vero cells.
Animals ; Vero Cells ; Autophagy/genetics* ; Chlorocebus aethiops ; Epidermal Growth Factor/pharmacology* ; Gene Expression Profiling ; Transcriptome ; Cell Survival

Gastroesophageal reflux disease (GERD) is a chronic digestive system disorder triggered by multiple factors, which is clinically prevalent and affects patients' quality of life. Laparoscopic fundoplication serves as the mainstay of surgical treatment for GERD, requiring standardized preoperative examinations to assess patients' reflux status and esophageal motility for individualized selection of fundoplication techniques. Intraoperative regulation of the fundoplication tension with a bougie aims to balance the anti-reflux efficacy and the risk of postoperative dysphagia. Additionally, membranous anatomy research guided by embryonic development facilitates optimization of surgical approaches and provides a theoretical basis for surgical innovation. This article deeply discusses the status of GERD diagnosis and treatment, as well as the surgical anti-reflux mechanisms, from multiple aspects including pathogenesis, diagnosis, and surgical management. We also contemplate the existing challenges in the embryonic development and anatomy of the anti-reflux barrier.

Gastroesophageal reflux disease (GERD) is a chronic digestive system disorder triggered by multiple factors, which is clinically prevalent and affects patients' quality of life. Laparoscopic fundoplication serves as the mainstay of surgical treatment for GERD, requiring standardized preoperative examinations to assess patients' reflux status and esophageal motility for individualized selection of fundoplication techniques. Intraoperative regulation of the fundoplication tension with a bougie aims to balance the anti-reflux efficacy and the risk of postoperative dysphagia. Additionally, membranous anatomy research guided by embryonic development facilitates optimization of surgical approaches and provides a theoretical basis for surgical innovation. This article deeply discusses the status of GERD diagnosis and treatment, as well as the surgical anti-reflux mechanisms, from multiple aspects including pathogenesis, diagnosis, and surgical management. We also contemplate the existing challenges in the embryonic development and anatomy of the anti-reflux barrier.

Foregut surgery has emerged as a new discipline in recent years,gaining attention at home and abroad.It mainly focuses on benign diseases of the stomach and esophagus,covering conditions such as gastroesophageal reflux disease,achalasia,and bariatric metabolic surgery.However,in some countries,foregut surgery also includes malignant diseases,such as esophageal and gastric cancers.Robotic surgery,one of the most advanced techniques available,is increasingly applied in clinical practice.The unique ergonomic design of robotic surgical systems allows surgeons to control the instruments with greater precision and finesse,thereby minimizing damage to surrounding vital tissues and organs.Robotic surgery is gradually becoming a major focal point in the field of anterior foregut surgery.However,its curr-ent limitations in China include high equipment and maintenance costs,as well as strict requirements for operator qualifications and operating room conditions.As robotic technology continues to develop and improve,it is expected that robot-assisted surgery will play an increasingly important role in foregut surgery,helping doctors improve the quality of surgery and provide better treatment outcomes for patients.

Objective:To investigate the changes in plasma ghrelin and influencing factors of weight loss effects after laparoscopic sleeve gastrectomy combined with fundoplication surgery (LSGFD).Methods:The retrospective cohort study was conducted. The clinical data of 115 obesity patients who were admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from April to June 2023 were collected. There were 37 males and 78 females, aged (37±9)years. Of 115 pati-ents, 93 cases undergoing laparoscopic sleeve gastrectomy (LSG) were divided into the LSG group, and 22 cases undergoing LSGFD were divided into the LSGFD group. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for com-parison between groups. Count data were described as absolute numbers, and the chi-square test was used for comparison between groups. Repeated measurement data were analyzed using the repeated ANOVA, and their variances were tested using a spherical test. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Changes in preoperative and postoperative plasma ghrelin in two groups of patients. The plasma ghrelin of patients at preopera-tive and postoperative 6 months changed from (16±14)×10 2 ng/L to (10±4)×10 2 ng/L in the LSG group and changed from (12±11)×10 2 ng/L to (11±3)×10 2 ng/L in the LSGFD group. There was no significant difference in the time effect, inter group effect, and interaction effect of changes in plasma ghrelin between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=2.199, Fgroup=0.001, Finteraction=0.793, P>0.05). There was a significant difference in plasma ghrelin in the LSG group before and after surgery at 6 months ( t=4.148, P<0.05), and there was no significant difference in plasma ghrelin in the LSGFD group before and after surgery at 6 months ( t=0.622, P>0.05). (2) Changes in preoperative and postoperative weight loss and metabolic related indicators in two groups of patients. ① There was a significant difference in the time effect of changes in body mass between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=242.285, P<0.05), and there was no significant difference in the inter group effect and interaction effect of changes in body mass between the LSG group and the LSGFD group before and after surgery at 6 months ( Fgroup=1.163, Finteraction=0.606, P>0.05). There were significant differences in body mass in the LSG group or the LSGFD group before and after surgery at 6 months ( t=23.597, 14.680, P<0.05). ② There was a significant difference in the time effect of changes in body mass index (BMI) between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=382.431, P<0.05), and there was no significant difference in the inter group effect and interaction effect of changes in BMI between the LSG group and the LSGFD group before and after surgery at 6 months ( Fgroup=1.619, Finteraction=1.085, P>0.05). There were significant differences in BMI in the LSG group or the LSGFD group before and after surgery at 6 months ( t=25.645, 16.628, P<0.05). ③ There was a significant difference in the time effect of changes in excess weight loss (%EWL) between the LSG group and the LSGFD group after surgery at 1 to 6 months ( Ftime=666.136, P<0.05), and there was no significant difference in the inter group effect and interaction effect of changes in %EWL between the LSG group and the LSGFD group after surgery at 1 to 6 months ( Fgroup=0.127, Finteraction=0.498, P>0.05). ④ There was no significant difference in the time effect, inter group effect, and interaction effect of changes in fasting blood glucose between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=1.573, Fgroup=1.872, Finteraction=0.948, P>0.05). There was a significant difference in fasting blood glucose in the LSG group before and after surgery at 6 months ( t=2.675, P<0.05), and there was no significant difference in fasting blood glucose in the LSGFD group before and after surgery at 6 months ( t=1.074, P>0.05). ⑤ There were significant differences in the inter group effect and interaction effect of changes in triglyceride between the LSG group and the LSGFD group before and after surgery at 6 months ( Fgroup=8.419, Finteraction=3.180, P<0.05), and there was no significant diffe-rence in the time effect of changes in triglyceride between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=1.398, P>0.05). Results of individual effect shown that there was no significant difference in triglyceride in the LSG group or the LSGFD group before and after surgery at 3 months ( F=2.956, 3.248, P>0.05), and there were significant differences in trigly-ceride in the LSG group or the LSGFD group after surgery at 1 month and 6 months ( F=14.152, 3.477, P<0.05). There was a significant difference in triglyceride in the LSG group before and after surgery at 6 months ( t=3.164, P<0.05), and there was no significant difference in triglyceride in the LSGFG group before and after surgery at 6 months ( t=0.023, P>0.05). ⑥ There were significant differences in the time effect and inter group effect of changes in total cholesterol between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=3.662, Fgroup=7.591, P<0.05), and there was no significant difference in the interaction effect of changes in total cholesterol between the LSG group and the LSGFD group before and after surgery at 6 months ( Finteraction=0.626, P>0.05). There was a significant difference in cholesterol in the LSG group before and after surgery at 6 months ( t=3.253, P<0.05), and there was no significant difference in total cholesterol in the LSGFG group before and after surgery at 6 months ( t=1.567, P>0.05). ⑦ There were significant differences in the time effect and inter group effect of changes in uric acid between the LSG group and the LSGFD group before and after surgery at 6 months ( Ftime=15.306, Fgroup=4.244, P<0.05), and there was no significant difference in the interaction effect of changes in uric acid between the LSG group and the LSGFD group before and after surgery at 6 months ( Finteraction=0.968, P>0.05). There were significant differ-ences in uric acid in the LSG group or the LSGFG group before and after surgery at 6 months ( t=6.152, 3.660, P<0.05). (3) Analysis of influencing factors on postoperative weight loss effects. Results of multivariate analysis showed that preoperative BMI, postoperative 6 months plasma ghrelin were independent protective factors for postoperative weight loss effects ( odds ratio=0.881, 0.673, 95% confidence interval as 0.817-0.950, 0.577-0.787, P<0.05). Conclusions:The decrease in plasma ghrelin in patients after LSGFD is not as obvious as that in patients after LSG, but it can achieve the same weight loss and metabolic improvement effects as after LSG. The lower preoperative BMI and postoperative 6 months plasma ghrelin are independent protective factors for postoperative weight loss effects.

Hiatal hernia (HH) is a common benign disease in the digestive system, where the stomach or other internal organs bulges and displaces into posterior mediastinum through the esophageal hiatus on the diaphragm, often accompanied by symptoms such as heartburn, acid reflux, and chest pain. Patients with symptoms that are unresponsive to medical treatment require surgical intervention for relief. In recent years, robotic-assisted surgery (RAS) has rapidly advanced, offering precise manipulation, three-dimensional visualization, and a flexible wrist-turning robotic arm, capable of filtering out hand tremors. These advantages have led to the increasing use of RAS in HH repair procedures. This article provides a summary and analysis of RAS for the treatment of HH.

Protease activating receptor (PAR) is a member of G protein-coupled receptor family, which includes four subtypes, namely PAR1, PAR2, PAR3 and PAR4. Except PAR2 trypsin receptor, other subunits belong to thrombin receptor. These receptors exist widely in various tissues of the body, especially in the digestive system to play a certain biological effect. In recent ten years, studies have shown that PAR1 and PAR2 play a key role in immune inflammatory response, which has aroused people′s attention. At present, it is of clinical value to study the development of gastroesophageal reflux disease (GERD) by exploring the unique activation mode of PAR2 in the pathological processes of esophageal mucosal damage, pain transmission, immune inflammatory response, stress and so on. This review aims to elucidate the molecular mechanism of PAR2 in gastroesophageal inflammation.

Protease activating receptor (PAR) is a member of G protein-coupled receptor family, which includes four subtypes, namely PAR1, PAR2, PAR3 and PAR4. Except PAR2 trypsin receptor, other subunits belong to thrombin receptor. These receptors exist widely in various tissues of the body, especially in the digestive system to play a certain biological effect. In recent ten years, studies have shown that PAR1 and PAR2 play a key role in immune inflammatory response, which has aroused people′s attention. At present, it is of clinical value to study the development of gastroesophageal reflux disease (GERD) by exploring the unique activation mode of PAR2 in the pathological processes of esophageal mucosal damage, pain transmission, immune inflammatory response, stress and so on. This review aims to elucidate the molecular mechanism of PAR2 in gastroesophageal inflammation.

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15^CKO) or Tbc1d15 knockin (Tbc1d15^CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.