Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

The long-term efficacy and complications of implantable diaphragm pacer (IDP) in a child with cervical spinal cord injury (CSCI) in the Department of Spinal and Neural Functional Reconstruction, China Rehabilitation Research Center in September 2022 were retrospective analyzed.A male child had quadriplegia without an obvious cause at the age of 12 years, and he was then lived completely with the assistance of mechanical ventilation.At the age of 14 years, he could wean off the ventilator in unilateral diaphragmatic pacing mode.However, mechanical ventilation was re-given for months after 5 years due to pneumonia, and then the IDP was re-given with the self-felt decreased pacing effect.After hospitalization, the patient was examined with mild diaphragmatic atrophy, secondary flat chest, and mild scoliosis.After optimization of the transdiaphragmatic pacing threshold and rehabilitation, his respiratory function improved.IDP can be used in CSCI for long time, while flat chest and scoliosis that limited the expansion of the lungs should be considered.At the meantime, the increased abdominal spasm affected the abdominal compliance, leading to the decrease in the efficiency of the diaphragm.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To investigate the expression of forkhead box protein O3(FOXO3) in pancreatic cancer and its effect on the motility and proliferation of pancreatic cancer cells.Methods:The FOXO3 expression in pancreatic cancer and adjacent tissues was retrieved from LinkedOmics database. Western blotting and real-time quantitative polymerase chain reaction were used to detect FOXO3 expression in pancreatic cancer cells and human pancreatic stellate cells. PANC-1 and MIAPaCa-2 pancreatic cancer cells with low FOXO3 expression were selected to transfect FOXO3 overexpression plasmid and negative control plasmid, respectively. The motility and proliferation ability of pancreatic cancer cells were detected by colony formation assay, cell scratch assay, Transwell assay and flow cytometry.Results:In the LinkedOmics database, the relative expression of FOXO3 protein in the cancer tissues of 64 patients with pancreatic cancer was significantly lower than that in the adjacent tissues ( t=8.36, P<0.001). The number of clones in PANC-1 cell line was (30.0±6.6) after overexpressed FOXO3, which was lower than that in negative control cells (92.7±6.7), and the difference was statistically significant ( t=11.54, P<0.001). After overexpressed FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the scratch repair rate was significantly decreased compared with the control group. In Transwell experiment, the number of cells in FOXO3 overexpressed group in PANC-1 cell lines was (21.0±6.6), which was lower than that of negative control groups (55.7±8.5), and the difference was statistically significant ( t=5.59, P=0.005). The results of MIAPaCa-2 cell line were consistent with that of PANC-1 cell line. After overexpressing of FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the proportion of cells in the G0/G1 phase decreased, while the proportion in the S phase increased. Conclusion:The expression of FOXO3 was decreased in pancreatic cancer. Overexpression of FOXO3 could significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells and induce cell cycle arrest, which is a potential target for the treatment of pancreatic cancer.

Photoperiod plays an important role in transformation from vegetative growth to reproductive growth in plants. CONSTANS (CO), as a unique gene in the photoperiod pathway, responds to changes of day length to initiate flowering in the plant. In this study, the expression level of FaCONSTANS (FaCO) gene under long-day, short-day, continuous light and continuous darkness conditions was analyzed by real-time quantitative PCR. We constructed the over-expression vector p1300-FaCO and infected into Arabidopsis thaliana by Agrobacterium-mediated method. We constructed the silencing vector p1300-FaCO-RNAi and infected into Festuca arundinacea by Agrobacterium-mediated method. The expression of FaCO gene was regulated by photoperiod. The over-expression of FaCO promoted flowering in wild type of Arabidopsis thaliana under long day condition and rescued the late flowering phenotype in co-2 mutant of Arabidopsis thaliana. Silencing FaCO gene in Festuca arundinacea by RNAi showed late-flowering phenotype or always kept in the vegetative growth stage. Our understanding the function of FaCO in flowering regulation will help further understand biological function of this gene in Festuca arundinacea.
Arabidopsis/metabolism* ; Arabidopsis Proteins/genetics* ; Festuca/metabolism* ; Flowers/genetics* ; Gene Expression Regulation, Plant ; Photoperiod

Objective:To investigate the expression of IKBKE and NF-κB in pancreatic cancer, and to explore the effect of IKBKE on pancreatic cancer proliferation and migration.Methods:Immunohistochemistry staining was used to study the expression of IKBKE and NF-κB in tissues of 61 pancreatic cancer patients admitted to the Second Hospital of Tianjin Medical University from January 2012 to January 2017 and 13 normal pancreatic tissues. The correlations between those expression to clinicopathological features were analyzed. Lentivirus mediated RNAi was transfected into pancreatic cancer cells to block IKBKE. Western blot was performed to test the silencing effeciency; CCK-8 and plate clone and scratch assays were used to investigate the proliferation and migration of pancreatic cancer.Results:Immunohistochemical staining showed that 60 (98.4%) of IKBKE staining were weakly positive, positive, and strongly positive in pancreatic cancer tissues, which were significantly higher than normal pancreatic tissues(76.9% cases were weakly positive and the rest were negative), and the differences were statistically significant ( P<0.05). All cases of NF-κB exhibited weakly positive expression and above in pancreatic cancer tissues, which was markedly higher than normal tissues (30.8% cases were weak positive and the rest were negative staining), statistically significant ( P<0.05). Survival analysis showed that patients with high level of IKBKE showed a shorter overall survival ( P<0.05). CCK-8, plate cloning and scratch assays showed that the proliferation and migration of were significantly decreased in IKBKE knocking down group ( P<0.05). Conclusions:IKBKE and NF-κB are highly expressed in pancreatic cancer, and IKBKE is correlated with NF-κB in pancreatic cancer. Blocking of IKBKE could distinctly inhibit the proliferation and migration of pancreatic cancer.

Objective:To discuss the efficacy and safety of ultrasound-guided rectus sheath block (RSB) combined with subcostal transversus abdominis plane block(TAPB) in peritoneal dialysis catheter implantation in patients with end-stage renal disease.Methods:A total of sixty patients (scheduled for elective peritoneal dialysis catheter placement from June 2018 to March 2019 in Wuhan First Hospital were randomly divided into two groups: local anesthesia group(group LA, 30 patients) and ultrasound-guided RSB combined with subcostal TAPB (group NB, 30 patients). Group LA: local infiltration anesthesia was performed with 1% lidocaine and 0.5% ropivacaine 20ml; group NB: RSB, 1% lidocaine and 0.5% ropivacaine 15 ml were injected into the lateral rectus sheath, and TAPB, 1% lidocaine and 0.5% ropivacaine 20 ml were injected into the transversus abdominis plane. Mean arterial blood pressure (MAP) and heart rate (HR) were recorded at the point of entering the operating room (T 0), after anaesthesia (T 1), at the beginning of operation (T 2), twenty minutes after the beginning of operation (T 3), and at the end of the operation (T 4). The duration of operation, the times of additional local anesthetia during the surgery, the score of visual analogue scale (VAS) during and 24 h after the surgery, the rate of alteration to general anesthesia and the occurrence of adverse reactions were recorded. Results:In group LA, compared with T 0, MAP and HR at T 2 and T 3 increased significantly: (93.1 ± 9.7), (99.8 ± 11.6) times/min vs. (78.4 ± 10.5) times/min and (105.1 ± 13.7), (110.5 ± 14.4) mmHg (1 mmHg = 0.133 kPa) vs. (92.1 ± 12.8) mmHg, P<0.05. In group NB, there were no differences among T 0-T 4. At T 2 and T 3, MAP and HR in group LA were higher than those in group NB ( P<0.05). Compared with that in group LA, the duration of operation time decreased significantly in group NB ( P<0.05). The times of additional local anesthetia during the surgery in group LA were more than those in group NB ( P<0.05). Compared with those in group LA, the VAS scores during and 24 h after the surgery in group NB were significantly lower: (3.25 ± 0.65) scores vs. (5.85 ± 0.76) scores, (1.46 ± 0.57) scores vs. (2.37 ± 0.45) scores, P<0.05. There were no significant differences in the rate of alteration to general anesthesia between the two groups: 3.33% (1/30) vs. 0, P>0.05. There was no adverse reaction in these two groups. Conclusions:Ultrasound-guided rectus sheath block combined with subcostal transversus abdominis plane block is safe and effective in peritoneal dialysis catheter implantation. The effect of intraoperative anesthesia is definite, with little influence on hemodynamics. The postoperative analgesia effect is good, without obvious anaesthesia-related adverse events.

Objective To study the clinical value of retroperitoneoscope-assisted intraperitoneal approach in the treatment of large renal tumors.Methods A total of 89 patients with large renal tumors (d ＞7 cm) were involved from January 2014 to December 2017.Among them,32 cases were treated by retroperitoneoscope-assisted intraperitoneal approach (group A),including 18 males and 14 females,aged (63.5±7.5)years,with 20 cases on the left and 12 on the right,and mean tumor diameter of (7.9 ± 0.6).Thirty cases were treated by laparoscopy (group B),including 17 males and 13 females,aged (64.5 ±7.3)years,with 16 cases on the left and 14 cases on the right,and the average tumor diameter of (7.6 ±0.7) cm.Twenty-seven cases underwent open surgery (C group),including 15 males and 12 females,aged (64.9 ±5.7) years,with 13 cases on the left side and 14 cases on the right,and the average tumor diameter of (7.9 ±0.6) cm.There was no statistically significant difference among the three groups in term of demographics (P ＞ 0.05).The clinical data was collected and statistical analysis was made for comparison among the three groups,including operation time,blood loss,surgical complications,postoperative intestinal recovery and postoperative hospital stay.All the patients were with single renal tumor,and no other major comorbidities were found.Results All of the 89 surgeries were successful.Hypercapnia was found in 2 cases (6.3％) in Group A,and recoverd 15 minutes after stopping pneumoperitoneum and anesthesia.The operation time was 120-200 minutes with an average of (155.0 ± 22.1) minutes.The average amount of bleeding was (141.6 ± 33.8) ml.Bowel recovered 3 (3-5) days after operation.The patients were hospitalized for 7 (7-9) days.In group B,hypercapnia was found in 2 patients (6.7％) and recoverd after stopping pneumoperitoneum and anesthesia.The time of operation was (184.2 ± 20.6) min,the amount of bleeding was (191.5 ± 46.2) ml,the bowel recovered 4 (4-6) days after operation,and the postoperative hospitalization duration was 7.5 (6-9) days.The operation time of group C was (54.0 ± 16.6) min,blood loss was (309.6 ± 50.2) ml,postoperative intestinal recovery was 5 (4-6)days,and the postoperative hospitalization time was 8 (7-12)days.Group A had less operation time than Group B(P ＜0.05),and no difference with Group C(P ＞0.05).Group A had advantages in term of blood loss and postoperative intestinal recovery time compared with B and C (P ＜ 0.05).Groups A and B had no difference in term of surgical complications and postoperative hospital stay (P ＞ 0.05),but both of the two groups had obvious advantages over group C (P ＜ 0.05).Conclusions Retroperitoneoscopeassisted intraperitoneal approach is the synergetic application of two endoscopic approaches,which is superior to any single operation for the treatment of large renal tumor,such as less bleeding,shorter operation time,faster postoperative recovery,and so on.This method not only reduces the difficulty of operation,provides an alternative for laparoscopic treatment of large renal tumors,but also has a good application for complex renal tumors complicated with renal vein and inferior vena cava tumor thrombus.

AIM:To investigate the roles of ClC-3 chloride channels in the regulation of cell cycle and the re-lationship between ClC-3 chloride channels and the cell cycle regulators , such as cyclin D1, cyclin-dependent kinase (CDK)4, CDK6, P21 and P27 in the HeLa cells.METHODS:ClC-3 genes were silenced by the siRNA technique in the HeLa cells.The transfection efficiency of ClC-3 siRNA was detected by real-time PCR.The cell cycle distribution was ana-lyzed by the flow cytometry .The protein expression of ClC-3, P21, P27, CDK4, CDK6 and cyclin D1 was determined by Western blot .RESULTS:ClC-3 was knocked down by ClC-3 siRNA in the HeLa cells .Transfection of the cells with ClC-3 siRNA arrested the cells at G0/G1 phases, decreased the expression of cyclin D1, CDK4 and CDK6, and increased the expression of P21 and P27.CONCLUSION:ClC-3 plays an important role in the cell cycle of HeLa cells through the G 1-S transition point.ClC-3 may regulate the cell cycle progression by up-regulation of cyclin D1, CDK4 and CDK6 expression and/or by down-regulation of P21 and P27 expression.

Objective To survey the attitudes and acceptance level of upper limb function reconstruction in patients with cervical spinal cord injury and analyze the related factors. Methods From October, 2013 to June, 2014, a total of 104 patients with cervical spinal cord injury were surveyed with self-designed questionnaire. Results There were 81 valid questionnaires, in which 3 patients (3.7%) heard of upper-extremity reconstructive surgery. The patients longed for upper limb function improvement most. After they had a understanding of the surgery, their willingness improved (P<0.01). No significant difference was found in the satisfaction degree and operation willingness between different hand function groups (P>0.05). The patients focused on the operation cost, the operation risk, recovery time after operation and the satisfaction of assistive devices, however, they were not correlated with the willingness of upper limb function reconstruction (P>0.05). Conclusion There is a clear gap between strong desire for functional improvement of upper limb and surgery awareness. It is important to communicate upper limb among patients with cervical spinal cord injury.