Objective To investigate the effect of progesterone receptor membrane component 1(PGRMC1)mediated autophagy on the sensitivity of liver cancer cells to 125I particles irradiation.Methods Hepatoma cell lines Huh7 and LM3 were exposed to different doses(0,2,4,6 and 8 Gy)of 125I particles,and cell autophagy was observed by transmission electron microscopy(TEM).Then,autophagy inhibitor chloroquine(CQ),agonist rapamycin(Rapa),and PGRMC1 inhibitor AG-205 were used respectively to verify that PGRMC1-mediated autophagy plays a key role in the sensitivity of hepatocellular carcinoma cells to 125I particle irradiation.Cell proliferation,colony formation and apoptosis were detected by CCK-8 assay,clonal formation test and flow cytometry,respectively.The expression levels of PGRMC1,microtubule-associated protein light chain 3-Ⅰ(LC3-Ⅰ),LC3-Ⅱ and p62 were detected by Western blotting.Results Different doses of 125I particles irradiation significantly decreased the proliferation and clonogenesis of Huh7 and LM3 cells(P＜0.05),and increased the apoptotic cells(P＜0.01),in a dose-dependent manner.Compared with the 0 Gy group,the ratio of LC3-Ⅱ/LC3-Ⅰ in Huh7 and LM3 cells was obviously increased,and the expression of p62 was significantly down-regulated in the 6 Gy group.The proliferation capacity and clonal formation ability of Huh7 and LM3 cells were decreased significantly,and their apoptotic cells were increased notably in the 6 Gy+CQ group than the 6 Gy group,while the above results were on the contrary in the 6 Gy+Rapa group.The 6 Gy+AG205 group had notably decreased LC3-Ⅱ/LC3-Ⅰ ratio in the Huh7 and LM3 cells,up-regulated p62 expression,reduced cell proliferation capacity and clone formation ability,and enhanced cell apoptosis when compared with the 6 Gy group,and the above results of the 6 Gy+PGRMC1 group were opposite.Conclusion Increment of PGRMC1 induced by 125I irradiation can promote autophagy,increase the proliferation and clonogenesis,and reduce the apoptosis in hepatocellular carcinoma cells.

To investigate the expression and clinical significance of GATA-3 and H3K27me3 in Tibetan patients with bladder urothelial carcinoma (BUC).

Objective:To observe any effect of bilateral high-frequency repetitive transcranial magnetic stimulation (rTMS) of the cerebellum on the swallowing of stroke survivors with dysphagia.Methods:Thirty-eight patients with post-stroke dysphagia were randomly divided into a cerebellar stimulation group of 20 and a sham group of 18. In addition to drug therapy and physical rehabilitation training, the cerebellar stimulation group received 500 pulses of rTMS of the cerebellum daily at 10Hz and 120% of the resting movement threshold lasting 1s at 9s intervals. The sham stimulation group was treated with sham rTMS (with the angle between the stimulation coil and the scalp at 90°). Twenty minutes later, both groups were given 30 minutes of routine swallowing training daily by the same speech therapist. The treatment was administered 5 times a week for 3 weeks. Before the treatment and afterward, both groups′ swallowing was evaluated y videofluoroscopic swallowing study (VFSS), using a functional dysphagia scale (FDS) and using the Rosenbek penetration aspiration scale (PAS). Oral transport time, swallowing response time, pharyngeal transport time, laryngeal vestibular closure time and upper esophageal sphincter opening duration were recorded, and the changes in swallowing function and swallowing time parameters before and after the treatment were compared between the two groups.Results:Before the stimulation there were no significant differences between the two groups. Afterward, the average PAS and FDS scores of both groups had improved significantly, but with significantly greater improvement in the cerebellar stimulation group than in the sham group. Average oral transit time and swallow response time had shortened significantly, but with significantly shorter time, on average, in the cerebellar stimulation group.Conclusion:Bilateral high-frequency rTMS of the cerebellum can improve the swallowing of persons with dysphagia, and shorten their oral transit time and swallow response time.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1^Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1^Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Objective:To observe the clinical effectiveness of manual therapy based on posture decoding for patients with lower crossed syndrome (LCS).Methods:Thirty-six LCS patients were randomly divided into an observation group and a control group, each of 18. The observation group received manual therapy based on posture decoding, while the control group was treated with proprioceptive neuromuscular facilitation (PNF), both in 20min sessions, once a week for 4 weeks. Before the experiment, after one, two and four weeks of treatment and followed-up 4 and 8 weeks later, both groups were evaluated using a visual analogue scale (VAS), the Oswestry Disability Index (ODI) and finger-floor distance (FFD). Anterior pelvic tilt angles (ASIS-PSISs), sacral slopes (SS), lumbar curve index (LCI) and surface EMG flexion-relaxation ratios (FRRs) were also recorded from both groups before and after the treatment.Results:After one and four weeks of the treatment, the average VAS, ODI, and FFD had decreased significantly in both groups, with all significantly lower in the observation group, on average. At the final follow-up, the average VAS and ODI scores of both groups were significantly lower than before the treatment, with those of the observation group significantly lower than the control group′s averages. After 4 weeks of treatment significant differences were observed also in the group′s average ASIS-PSISs, SSs and LCIs compared with before the treatment. And right after the treatment the left and right surface electromyography FRRs of the observation group were significantly higher than those of the control group.Conclusion:Manual therapy based on posture decoding can significantly improve the pelvis forward angle and lumbar motion of LCS patients, relieving back pain and relaxing back muscles.

Objective: To investigate the regulatory effect and mechanism of specific antagonist of acid-sensitive ion channel 3 (APETx2) on visceral sensitivity in mice with post-infectious irritable bowel syndrome (PI-IBS) ． Methods: The PI-IBS model was established by National Institutes of Health (NIH) mice infected with Trichinella spiralis．Gastrointestinal transport function was assessed by measuring the time to first black stool and the number of fecal pellets collected for 6 hours ; abdominal wall withdrawal reflex (AWR) was used to assess visceral sensitivity ; the expression of calcitonin gene-related peptide ( CGRP) in the colon tissue was detected by immunohistochemistry ; the expression of brain-derived neurotrophic factor (BDNF) and CGRP mRNA in the colon tissues was detected by quantitative real time polymerase chain reaction ( qRT-PCR) ． The expression levels of acid sensing ion channel 3 (ASIC3) ，CGRP，and transient receptor potential vanilloid 1 (TRPV1) protein in brain tissue were detected by Western blot analysis. Results: Compared with the control group，the PI-IBS group significantly reduced the time of first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the protein expression of CGRP in colon tissue，BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased．Compared with the control group，the PI-IBS group significantly reduced the time to first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased ; compared with the PI-IBS group，the first time of black stool clearance in the APETx2 group was significantly prolonged，the number of fecal particles and AWR score within 6 hours were significantly reduced，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA was significantly reduced，the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue was significantly reduced，and the difference was statistically significant (P＜0. 05) ． Conclusion APETx2 can alleviate visceral sensitivity and regulate gastrointestinal motility in PI-IBS mice by downregulating the expression of BDNF，CGRP，ASIC3 and TRPV1．APETx2 may provide a new therapeutic option for the treatment of IBS.

Objective:To investigate the etiology, prognosis and clinical characteristics of abnormal serum amylase and lipase in children.Methods:This study was a retrospective study.A total of 7 813 children older than 28 days who had their serum amylase and lipase detected in Hunan Children′s Hospital from August 2017 to August 2020 were included as the study subjects.Children with acute and chronic pancreatitis were excluded.The age, gender, impatient department, imaging exams, discharge outcomes, main diagnosis, diagnostic ICD10 code, and the highest values of serum amylase and lipase during hospitalization were collected through the medical record system.According to the levels of serum amylase and lipase, the children were divided into 3 groups.Patients in group A had normal serum amylase and serum lipase levels.The serum amylase or lipase levels of patients in group B was 1 to 3 times higher than that of group A. The serum amylase or lipase levels in group C was 3 times higher than that of group A. Group B and group C had abnormal pancreatic enzyme levels.According to the prognosis, patients were divided into the survival group and the death group.The relationship of the occurrence of abnormal serum amylase and lipase levels with the age, sex, disease type and prognosis of children was analyzed.Results:The ratio of abnormal trypsin in male and female was 11.5% and 12.9%, respectively.The number of children with abnormal pancreatic enzyme levels in the 28 day -1 year old group, >1-3 years old group, >3-6 years old group, >6 -12 years old group and > 12 year old group were 37 cases (4.6%), 185 cases (15.4%), 199 cases (10.5%), 431 cases (13.9%), and 94 cases (11.7%), respectively.The mortality rate was 1.6% (112/6 867 cases) in group A, 5.2% (32/617 cases) in group B, and 7.6% (25/329 cases) in group C. The mortality risk of group B and C was both higher than that of group A. Compared with group A, the OR (95% CI) of group B and group C was 3.30 (2.21-4.93) and 4.96 (3.17-7.77), respectively.In group C, the top five diseases were parotitis (26.4%), cholangiectasis (11.6%), choledochal cysts (8.5%), gastroenteritis (4.5%) and sepsis (3.3%). Conclusions:Pancreatic enzyme abnormalities in children are associated with adverse prognosis.Pancreatic enzyme abnormalities are more prone to occur in children aged >1-3 with mumps, digestive diseases and congenital digestive system structural deformities.In addition, children with sepsis are also easy to present pancreatic enzyme abnormalities.Clinical attention should be paid to the possibility of secondary pancreatic damage in children with sepsis.

Objective:To investigate the status of post-traumatic growth and its afffecting factors in middle-aged and young patients with type 2 diabetes, in order to carry out clinical intervention for reference.Methods:A general data questionnaire, Posttraumatic Growth Inventory, Perceived Social Support Scale, and Connor-Davidson Resilience Scale were used to survey 222 middle-aged and young patients with type 2 diabetes hospitalized from December 2020 to March 2021 in Shandong First Medical University Affiliated Center Hospital, Shandong Provincial Qianfoshan Hospital, Liaocheng People′s Hospital.Results:The total score of Posttraumatic Growth Inventory, Perceived Social Support Scale, and Connor-Davidson Resilience Scale was (45.20 ± 12.90), (42.73 ± 10.16),(51.41 ± 10.60) points in middle-aged and young patients with type 2 diabetes. Regression showed that treatment mode, medical payment mode, social support, and psychological resilience were the main influencing factors of post-traumatic growth levels in middle-aged and young patients with type 2 diabetes ( P<0.05), which could explain 42.3% of the variation. Conclusions:Middle-aged and young patients with type 2 diabetes have grown at low level. Medical staff should concentrate on the positive psychology of patients and improve their level of social support and resilience to promote the production of post-traumatic growth.

Objective:To identify a novel bombesin bioactive peptide from the skin secretion of Hylarana Latouchii, and to explore its effect on insulin secretion in islet cells.Methods:The skin secretion from Hylarana Latouchii was extracted by electrical stimulation, and the single chain of bombesin peptide was cloned and sequenced. The peptide QUB2995 was synthesized via solid-phase synthesis, then purified using reversed-phase high performance liquid chromatography (HPLC). Matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF) was applied to validate. QPCR and ELISA were used to probe the effect of QUB2995 on insulin secretion in MIN6 and INS-1 cells.Results:A novel bombesin peptide named QUB2995 (GAFGDFLKGAAKA GALKILSIAQCKLSGTC) was found in the skin secretion of Hylarana Latouchii through molecular cloning. The bioactive peptide could significantly promote the proliferation and insulin secretion from mouse islet MIN6 cells and rat islet INS-1 cells. The effect reached a climax at the concentration of 10 -5 mol/L. Conclusion:A novel bombesin bioactive peptide named QUB2995 was found from Hylarana Latouchii. It could significantly promote insulin secretion in MIN6 cells of mouse islets and INS-1 cells of rat islets, indicating its potential in the treatment of diabetes.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.