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1.
Protein & Cell ; (12): 47-64, 2022.
Article in English | WPRIM | ID: wpr-922492

ABSTRACT

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.

2.
International Journal of Surgery ; (12): 715-720, 2021.
Article in Chinese | WPRIM | ID: wpr-907511

ABSTRACT

Acute abdomen is often a general term for abdominal diseases with acute abdominal pain as the main manifestation. Common clinical acute abdomen includes acute appendicitis, acute cholecystitis, acute cholangitis, acute pancreatitis, gastrointestinal perforation, intestinal obstruction and other diseases, its characteristics are great changes, rapid progress, high misdiagnosis rate, high postoperative complication rate and high mortality rate, accurate diagnosis and early treatment can obtain a good prognosis. With our in-depth understanding of the occurrence and development of acute abdomen diseases and the development of evidence-based medicine, minimally invasive technology plays a pivotal role in the diagnosis and treatment of common acute abdomen. Laparoscopy on diagnosis can clarify disease diagnosis to a large extent. For those who cannot undergo surgery, decompression and drainage under endoscopy provides a diversified plan for treatment decisions. In addition, minimally invasive techniques are also used in etiological treatment and complications. Disease, prevention of recurrence in all aspects, Minimally invasive technology is beneficial to the etiological treatment of biliary pancreatitis, appendicitis and cholangitis, and endoscopic technology is more consistent with the minimally invasive concept in the treatment of complications.

3.
Acta Pharmaceutica Sinica ; (12): 445-455, 2021.
Article in Chinese | WPRIM | ID: wpr-873769

ABSTRACT

With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.

4.
Protein & Cell ; (12): 394-410, 2021.
Article in English | WPRIM | ID: wpr-880913

ABSTRACT

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

5.
Chinese Journal of Surgery ; (12): 114-118, 2020.
Article in Chinese | WPRIM | ID: wpr-787667

ABSTRACT

To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen's pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD). Clinical data of 116 consecutive patients who underwent LPD using Chen's pancreaticojejunostomy technique in Hunan Provincial People's Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen's pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes). The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2%(13/116) of cases had postoperative pancreatic fistula (POPF), including 10.3% (12/116) of biochemical fistula and 0.9%(1/116) of grade B POPF, no grade C POPF occurred; 10.3%(12/116) had gastrojejunal anastomotic bleeding; 3.4%(4/116) had hepaticojejunal anastomotic fistula; 3.4%(4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1%(14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7%(2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Chen's pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

6.
Article in Chinese | WPRIM | ID: wpr-856396

ABSTRACT

Objective: To investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice. Methods: Eighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups ( n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR). Results: All nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group ( P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group ( P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups ( P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant ( P<0.05). Conclusion: The level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.

7.
International Journal of Surgery ; (12): 82-86,封4, 2020.
Article in Chinese | WPRIM | ID: wpr-863277

ABSTRACT

Objective To explore the safety and feasibility of laparoscopic liver resection in the treatment of intrahepatic cholangiocarcinoma (ICC).Methods The retrospective study was adopted.The clinical data of 58 patients with ICC who underwent laparoscopic liver resection in the Department of Hepatobiliary Minimally Invasive Surgery of the First Affiliated Hospital of Hu'nan Normal University were collected From January 2016 to December 2018.Among them,34 patients were males and 24 were females,aged from 34 to 71 years with a median age of 54 years.Observation indicators:(1) Surgical treatment:surgical methods,operation time,intraoperative blood loss,intraoperative blood transfusion rate,intraoperative hepatic portal blocking time,conversion rate,postoperative complications,postoperative hospital stay.(2) Postoperative pathological conditions.(3) Followup.Follow-up visits were conducted using an outpatient clinic and telephone to understand patient survival after surgery.The follow-up period was until June 2019.Measurement data with normal distribution were expressed as (Mean ± SD),count data was expressed as frequency and percentage.Results A total of 58 patients were included in this study,of which 48 patients underwent laparoscopic radical surgical resection of intrahepatic cholangiocarcinoma and 10 patients underwent laparoscopic conversion to laparotomy.(1) Surgical treatment:laparoscopic resection of the left liver (segments Ⅱ,Ⅲ and Ⅳ),laparoscopic resection of the right liver (segments Ⅴ,Ⅵ,Ⅶ and Ⅷ),laparoscopic resection of the right posterior lobe (segments WⅥ and Ⅶ),laparoscopic extended resection of the right posterior lobe,laparoscopic resection of the middle lobe (Ⅳ,Ⅴ and Ⅷ),laparoscopic resection of the Ⅴ and Ⅵ,laparoscopic resection of the left liver (segments Ⅱ,Ⅲ and Ⅳ)combined with the caudate lobe (segments Ⅰ and Ⅸ),laparoscopic extended left hemihepatectomy,laparoscopic resection of the Ⅵ,laparoscopic resection of the Ⅶ and Ⅷ,laparoscopic resection of the left lateral lobe (segments Ⅱ and Ⅲ) and laparoscopic resection of the right hepatic mass;operation time:(320.38 ± 107.68) min;intraoperative blood loss:(262.34 ± 76.06);intraoperative blood loss:0 (0/58);Intraoperative hepatic portal occlusion time:(48 ± 15) min,the conversion rate was 17.2% (10/58);the incidence of postoperative biliary fistula was 6.8% (4/58),and the patient was discharged after conservative treatment and unobstructed drainage (T-tube vacuum suction);the postoperative gastrointestinal recovery time was (1.84 ± 0.57) d;no other serious complications occurred.Postoperative hospital stay:(9.34 ± 3.39) d;there were no deaths and unplanned surgeries during the perioperative period.(2) Pathological conditions:32 cases received lymph node dissection during the operation,and 26 cases showed cholangiocarcinoma without lymph node dissection;pathological examination showed that the pathological reports of all tumor margins were negative,and 4 cases showed lymph node dissection and positive lymph node metastasis.(3) Follow-up results:of the 58 patients with ICC,49 were followed up for 6 to 36 months.The tumor survival time was (4 to 36) months.28 patients survived without tumor.17 patients had intrahepatic metastasis with multiple lymph node metastasis.4 patients were treated with microwave ablation after intrahepatic metastasis was found.9 patients were lost to follow-up.Conclusion Laparoscopic treatment of intrahepatic cholangiocarcinoma is safe and feasible in experienced centers.

8.
International Journal of Surgery ; (12): 82-86,f4, 2020.
Article in Chinese | WPRIM | ID: wpr-799705

ABSTRACT

Objective@#To explore the safety and feasibility of laparoscopic liver resection in the treatment of intrahepatic cholangiocarcinoma (ICC).@*Methods@#The retrospective study was adopted. The clinical data of 58 patients with ICC who underwent laparoscopic liver resection in the Department of Hepatobiliary Minimally Invasive Surgery of the First Affiliated Hospital of Hu′nan Normal University were collected From January 2016 to December 2018. Among them, 34 patients were males and 24 were females, aged from 34 to 71 years with a median age of 54 years. Observation indicators: (1) Surgical treatment: surgical methods, operation time, intraoperative blood loss, intraoperative blood transfusion rate, intraoperative hepatic portal blocking time, conversion rate, postoperative complications, postoperative hospital stay. (2) Postoperative pathological conditions. (3) Follow-up.Follow-up visits were conducted using an outpatient clinic and telephone to understand patient survival after surgery. The follow-up period was until June 2019. Measurement data with normal distribution were expressed as (Mean±SD), count data was expressed as frequency and percentage.@*Results@#A total of 58 patients were included in this study, of which 48 patients underwent laparoscopic radical surgical resection of intrahepatic cholangiocarcinoma and 10 patients underwent laparoscopic conversion to laparotomy. (1) Surgical treatment: laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ), laparoscopic resection of the right liver (segments Ⅴ, Ⅵ, Ⅶ and Ⅷ), laparoscopic resection of the right posterior lobe (segments Ⅵ and Ⅶ), laparoscopic extended resection of the right posterior lobe, laparoscopic resection of the middle lobe (Ⅳ, Ⅴ and Ⅷ), laparoscopic resection of the V and Ⅵ, laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ) combined with the caudate lobe (segments I and Ⅸ), laparoscopic extended left hemihepatectomy, laparoscopic resection of the VI, laparoscopic resection of the Ⅶ and Ⅷ, laparoscopic resection of the left lateral lobe (segments Ⅱ and Ⅲ) and laparoscopic resection of the right hepatic mass; operation time: (320.38±107.68) min; intraoperative blood loss: (262.34±76.06); intraoperative blood loss: 0 (0/58); Intraoperative hepatic portal occlusion time: (48±15) min, the conversion rate was 17.2% (10/58); the incidence of postoperative biliary fistula was 6.8% (4/58), and the patient was discharged after conservative treatment and unobstructed drainage (T-tube vacuum suction); the postoperative gastrointestinal recovery time was (1.84±0.57) d; no other serious complications occurred.Postoperative hospital stay: (9.34±3.39) d; there were no deaths and unplanned surgeries during the perioperative period. (2) Pathological conditions: 32 cases received lymph node dissection during the operation, and 26 cases showed cholangiocarcinoma without lymph node dissection; pathological examination showed that the pathological reports of all tumor margins were negative, and 4 cases showed lymph node dissection and positive lymph node metastasis. (3) Follow-up results: of the 58 patients with ICC, 49 were followed up for 6 to 36 months. The tumor survival time was (4 to 36) months. 28 patients survived without tumor. 17 patients had intrahepatic metastasis with multiple lymph node metastasis. 4 patients were treated with microwave ablation after intrahepatic metastasis was found. 9 patients were lost to follow-up.@*Conclusion@#Laparoscopic treatment of intrahepatic cholangiocarcinoma is safe and feasible in experienced centers.

9.
Chinese Journal of Surgery ; (12): 114-118, 2020.
Article in Chinese | WPRIM | ID: wpr-799375

ABSTRACT

Objective@#To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen′s pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD) .@*Methods@#Clinical data of 116 consecutive patients who underwent LPD using Chen′s pancreaticojejunostomy technique in Hunan Provincial People′s Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen′s pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed.@*Results@#All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes) . The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2% (13/116) of cases had postoperative pancreatic fistula (POPF) , including 10.3% (12/116) of biochemical fistula and 0.9% (1/116) of grade B POPF, no grade C POPF occurred; 10.3% (12/116) had gastrojejunal anastomotic bleeding; 3.4% (4/116) had hepaticojejunal anastomotic fistula; 3.4% (4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1% (14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7% (2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery.@*Conclusions@#Chen′s pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

10.
Chinese Journal of Surgery ; (12): 114-118, 2020.
Article in Chinese | WPRIM | ID: wpr-799374

ABSTRACT

Objective@#To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen′s pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD).@*Methods@#Clinical data of 116 consecutive patients who underwent LPD using Chen′s pancreaticojejunostomy technique in Hunan Provincial People′s Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen′s pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed.@*Results@#All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes). The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2%(13/116) of cases had postoperative pancreatic fistula (POPF), including 10.3% (12/116) of biochemical fistula and 0.9%(1/116) of grade B POPF, no grade C POPF occurred; 10.3%(12/116) had gastrojejunal anastomotic bleeding; 3.4%(4/116) had hepaticojejunal anastomotic fistula; 3.4%(4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1%(14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7%(2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery.@*Conclusions@#Chen′s pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

11.
Acta Pharmaceutica Sinica ; (12): 1735-1740, 2019.
Article in Chinese | WPRIM | ID: wpr-780308

ABSTRACT

With the significant breakthrough that programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) antibody drugs achieved promising clinical outcomes across various tumor types, immunotherapy targeting immune checkpoint has been considered a promising way to treat cancer. However, most recently studies suggest that the hyperprogressive disease occurred frequently during the therapy of using PD-1/PD-L1 antibody drugs and has become an urgent problem to be solved. In this review, we summarize the progress and potential reasons of hyperprogressive disease caused by PD-1/PD-L1 blockade, and further discuss its application based on the rational use of biomarkers for searching the benefit patients.

12.
Article in Chinese | WPRIM | ID: wpr-779542

ABSTRACT

Objective To understand the prevalence of synthetic drug use among man who have sex with man (MSM) in Nanjing and the associated factors. Methods MSM were recruited by snow-ball sampling, peer recommendation and network recruitment. Multivariate logistic regression analysis was performed to evaluate the correlated factors of recreational drug use. Results 29.6% of the 876 MSM ever used recreational drugs. The prevalence of HIV and syphilis infections were 9.5% and 9.0% respectively. After controlling the influence of correlated factors, recreational drug use was correlated with unprotected anal intercourse in the past 6 months(OR=1.83, 95% CI: 1.35-2.47, P<0.001), multiple male sex partnership in the past 6 months(OR=2.25, 95% CI: 1.65-3.05, P<0.001), higher HIV prevalence (OR=1.95, 95% CI: 1.21-3.17, P=0.007) and higher syphilis prevalence(OR=1.71, 95% CI: 1.02-2.84, P=0.040). Multivariate Logistic analysis showed that demographic and behavioral factors associated with recreational drug use including: less than 30 years old (OR=1.50, 95% CI: 1.07-2.11, P=0.020), self-identified as homosexual orientation (OR=1.65, 95% CI: 1.16-2.34, P=0.005), seeking male partners mainly via the internet(OR=1.58, 95% CI: 1.07-2.35, P=0.022), higher monthly income(OR=1.57, 95% CI: 1.13-2.17, P=0.007), receptive sexual role(OR=1.55, 95% CI: 1.04-2.32, P=0.033). Conclusions MSM has a high prevalence of recreational drug use in Nanjing, which was positively correlated with HIV/syphilis infection and high risk behaviors. Intervention efforts should be devoted to reduce and combat drug use among MSM.

13.
Article in Chinese | WPRIM | ID: wpr-817701

ABSTRACT

@#【Objective】To investigate the effects of up-regulating RA signal and inhibiting AP-1 transcriptional activity on TGF-β2 secretion by RPEs and its possible pathways.【Methods】① To investigate the effects of ATRA treat⁃ ment,human retinal pigment epithelial cell line ARPE-19 cells were divided into 5 groups:control group and 4 interven⁃ tion groups(6 h,12 h,24 h and 48 h after RA treatment). Western blot,RT-qPCR and immunofluorescence staining were carried out to analyze RARβ and c-Fos expression. ②To investigate the effects of RARβ inhibitor LE540 treatment on expression of RARβ and c-Fos that were induced by ATRA,ARPE-19 cells were divided into 4 groups:control group,ATRA group,LE540 group and ATRA+LE540 group. RARβ and c-Fos expression was assessed by western blot and RT-qPCR. ③ To investigate the effects of AP-1 inhibitor T-5224 treatment,ARPE-19 cells were divided into 4 groups:control group and treatment groups(12 h,24 h and 48 h after T-5224 treatment). EMSA was carried out to ana⁃ lyze the AP-1 DNA binding activity. ④To investigate the effects of LE540 and T-5224 administration on ATRA- induced TGF-β2 secretion,ARPE-19 cells were divided into 4 groups:control group,ATRA group,ATRA+LE540 group and ATRA+LE540 group. Western blot and ELISA were carried out to analyze TGF-β2 secretion in ARPE-19 cells.【Results】 RARβ level in ARPE-19 cells was significantly higher in treatment group than in control group after being treated with ATRA for 24 and 48 hours(P<0.05). C-Fos level was first up-regulated and then decreased. After treatment with ATRA for 6 and 12 hours,c-Fos expression were significantly upregulated(P<0.01),but at 48 h after treatment,their expression were significantly decreased to the level which had no statistical difference compared with the control group (P>0.05). The AP-1 DNA binding activity was significantly decreased in ARPE-19 cells after being treated with T-5224 for 24 and 48 hours(P<0.01). Compared with ATRA group,TGF-β2 secretion was statistically down-regulated after being treated with LE540 and T-5224 for 48 hours(P<0.05).【Conclusion】ATRA can induce TGF-β2 secretion in RPE cells through affecting RARβ expression and AP-1 transcriptional activity.

14.
Protein & Cell ; (12): 808-824, 2019.
Article in English | WPRIM | ID: wpr-757874

ABSTRACT

While the majority of all human cancers counteract telomere shortening by expressing telomerase, ~15% of all cancers maintain telomere length by a telomerase-independent mechanism known as alternative lengthening of telomeres (ALT). Here, we show that high load of intrinsic DNA damage is present in ALT cancer cells, leading to apoptosis stress by activating p53-independent, but JNK/c-Myc-dependent apoptotic pathway. Notably, ALT cells expressing wild-type p53 show much lower apoptosis than p53-deficient ALT cells. Mechanistically, we find that intrinsic DNA damage in ALT cells induces low level of p53 that is insufficient to initiate the transcription of apoptosis-related genes, but is sufficient to stimulate the expression of key components of mTORC2 (mTOR and Rictor), which in turn leads to phosphorylation of AKT. Activated AKT (p-AKT) thereby stimulates downstream anti-apoptotic events. Therefore, p53 and AKT are the key factors that suppress spontaneous apoptosis in ALT cells. Indeed, inhibition of p53 or AKT selectively induces rapid death of ALT cells in vitro, and p53 inhibitor severely suppresses the growth of ALT-cell xenograft tumors in mice. These findings reveal a previously unrecognized function of p53 in anti-apoptosis and identify that the inhibition of p53 or AKT has a potential as therapeutics for specifically targeting ALT cancers.

15.
Article in Chinese | WPRIM | ID: wpr-712933

ABSTRACT

[Objective]To investigate the effects of peripheral form-deprivation and central form-deprivation on em-metropization of infant rhesus monkeys.[Methods]Nineteen healthy infant rhesus monkeys,about 3 weeks of age,were divided into three groups of A(n=6),B(n=6)and C(n=7)by random.The monkeys from group A wore peripheral form-deprivation spectacle lenses over both of their eyes.The monkeys from group B wore central form-deprivation lenses over both of their eyes.The monkeys from group C were 0.00 Dlenses over both of their eyes as control.The monkeys'refractive error,corneal topography,vitreous chamber depth were measured at the start of lens wear and at 2 weeks,1.5 months, 2 months,3 months post-treatment. By these means,we can observe the changes of eye growth and refractive status dynamically.[Results]In group A,B and C,no statistically significant difference was observed between the right and left eyes in vitreous chamber depth and refractive errors pre-and post-treatment(P>0.05).During the course of study,the vitreous chamber depthelongated gradually and refractive status became less hyperopic in all animals.After 3 months'lens wear,the axial eyeball elongation amplitude(mm)of group A(peripheral form-deprivation group,1.25±0.36)monkeys was more obvious than that of group C(control group,0.55±0.19,P=0.001),but there was no statistically significant difference between group B(0.59±0.14)and C(P=0.807).The decrease of hyperopic degrees(D)of group A monkeys (-4.44±1.33)was more obvious than that of group C(-1.83±0.58,P=0.000).The eyes of group A monkeys appeared a remarkable myopic shift after treatment. No statistically significant difference was found between group B(-2.25±0.31) and C in hyperopic degrees reduction(P=0.383). Before and after lens wear,no statistically significant difference was found within or between groups in corneal Sim K values(P>0.05).[Conclusion]During the emmetropization process of infant rhesus monkeys,if the visual signals from peripheral retina are in conflict with those from central retina,the former will play a dominant role.

16.
China Pharmacy ; (12): 809-812, 2018.
Article in Chinese | WPRIM | ID: wpr-704681

ABSTRACT

OBJECTIVE:To observe the clinical efficacy and safety of different combination regimens of latanoprost combined with timolol in the treatment of primary open-angle glaucoma(POAG). METHODS:By 2×2 self-cross controlled regimen,a total of 50 POAG patients were selected from Sanya Municipal People's Hospital during Jan. 2014-Nov. 2016,and then divided into group A and B according to random number tablet,with 25 cases in each group. Group A received traditional regimens (Latanoprost eye drops,once every night,one drop each time+Timolol maleate eye drops,once in the morning and evening,one drop each time);after 8 weeks of treatment and 48 h washout period,group A was given modified regimen(Latanoprost eye drops,once every night,one drop each time+Timolol maleate eye drops,once every morning,one drop each time)for 8 weeks. Group B was given modified regimen;after 8 weeks of treatment and 48 h washout period,then was given traditional regimen for 8 weeks. The 24 h average intraocular pressure,peak and trough intraocular pressure before and after medication,ocular hemodynamics [end diastolic velocity(EDV),peak systolic velocity(PSV),resistance index(RI)] and ADR were recorded in 2 regimens. RESULTS:After received two regimens,24 h average intraocular pressure,peak and trough intraocular pressure, intraocular pressure fluctuation and RI were significantly lower than before treatment,while EDV and PSV were significantly higher than before treatment,with statistical significance(P<0.05). There was no statistical significance between 2 groups(P>0.05). The total incidence of ADR in patients receiving modified regimen was significantly lower than those receiving traditional regimen(4.0% vs. 22.0%),with statistical significance(P<0.05). CONCLUSIONS:In traditional combination regimen of latanoprost combined with timolol,the frequency of timolol use was changed from twice in the morning and evening to once in the morning,which doesn't influence therapeutic efficacy but reduce ADR.

17.
Article in Chinese | WPRIM | ID: wpr-699153

ABSTRACT

Objective To investigate the application value of two-step separation approach in laparoscopic hemihepatectomy.Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 81 patients who underwent laparoscopic hemihepatectomy in the People's Hospital of Hunan Provincial between January 2015 and December 2017 were collected.Patients underwent laparoscopic hemihepatectomy using two-step separation approach after preoperative assessment.Hepatic pedicle,hepatic vein and branches were processed in the liver parenchyma,without intrathecal anatomy.Observation indicators:(1) preoperative assessment,intraand post-operative recovery;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed up to February 2018.Patients with hepatolithiasis received abdominal CT reexaminations at 5-7 days postoperatively for observing postoperative residual stones,and patients with malignant tumor were regularly followed up for 1-3 years.Measurement data with normal distribution were represented as (x)±s.Count data were described as frequency and percentage.Results (1) Preoperative assessment,intra-and post-operative recovery:81 patients underwent preoperative blood biochemistry,tumor biomarker and imaging examinations,and remaining functional liver volume and a liver model in 9 patients were respectively calculated and built using the 3D reconstruction software and 3D printing technology.Of 81 patients,68 underwent left hemihepatectomy and 13 underwent fight hemihepatectomy;77 underwent successful laparoscopic hemihepatectomy using two-step separation approach,4 were converted to open operation,with a rate of 4.9% (4/81).Of 4 patients with conversion to open operation,1 had difficult tumor separation due to tumor invading port vein induced to close adhesion,1 had stone removal difficulties under laparoscopy due to hepatolithiasis,and 2 were converted to open operation due to severe liver cirrhosis induced to massive intraoperative bleeding.Of 81 patients,70 gained dividing line of hemiliver by intraoperatively hemihepatic blood flow occlusion,and then got effectively control of bleeding combined with Pringle blood flow occlusion,and 11 received Pringle blood flow occlusion in whole liver.Laparoscopic fluorescence imaging technology was intraoperatively used for 2 patients.Operation time,volume of intraoperative blood loss,rate of intraoperative blood transfusion and duration of hospital stay in 81 patients were respectively (206±42)minutes,(195±134)mL,11.1%(9/81) and (11.5+2.7)days.Eighty-one patients were complicated with bile leakage and were cured by conservative treatment,with a bile leakage incidence of 2.5% (2/81),and without severe complications,such as postoperative bleeding,hepatic dysfunction and subphrenic abscess.There was no perioperative death and reoperation within 30 days postoperatively.(2) Follow-up and survival situations:55 patients with hepatolithiasis were followed up and underwent CT examinations of upper abdomen at 5-7 days postoperatively,including 52 with depletion of stones;3 with residual stones received removal of stones by choledochoscope at 3 months postoperatively,without residual stones.Seventeen patients with malignant tumor were followed up for 12-36 months,with a median time of 15 months,16 had tumor-free survival,and 1 was complicated with intrahepatic metastasis at 1 year after resection of hepatocellular carcinoma,and then underwent transcatheter arterial chemoembolization (TACE) and survived with tumor.Nine patients with benign liver diseases had good recovery during follow-up.Conclusion Two-step separation approach that is rationally used in laparoscopic hemihepatectomy is safe,effective and convenient.

18.
Article in Chinese | WPRIM | ID: wpr-669147

ABSTRACT

Based on the bibliometrics and visualization research methods and periodicals from the database of CNKI as data sources,the paper deeply analyzes the literatures related to military medicine of China in terms of annual article publication trends,main research institutions,cooperative network of the research institutions,keywords,key research fields,and puts forward the suggestions of strengthening cooperation of the army and the people,attaching importance to technical and frontier research,etc.

19.
Chinese Traditional Patent Medicine ; (12): 2231-2235, 2017.
Article in Chinese | WPRIM | ID: wpr-668888

ABSTRACT

AIM To explore the effects of ligustrazine on blood rheology,aldose reductase (AR) and renal function in diabetic nephropathy (DN) rats.METHODS The DN rat model was established by intraperitoneal injection of streptozotoein (55 mg/kg),rats were randomly divided into five groups,model group,irbesartan [50 mg/(kg · d)] group,high-,middle-and low-dose of ligustrazine [200,100,50 mg/(kg · d)] groups,together with normal control group.All the rats received daily garage for eight successive weeks.At the end of experiment,blood rheology,blood glucose,aldose reductase in erythrocyte and kidney tissue,24 h urinary protein,blood urea nitrogen,creatinine,creatinine clearance and renal function were observed.RESULTS Compared with the model group,blood rheology,blood glucose and renal function in various treatment groups were effectively improved,and aldose reductase activity was significantly decreased (P < 0.05).HE staining and PAS staining showed that the pathological changes in kidney were significantly alleviated.CONCLUSION Ligustrazine can protect kidney of DN rats by ameliorating blood rheology,decreasing blood glucose and inhibiting aldose reductase activity.

20.
Article in Chinese | WPRIM | ID: wpr-668610

ABSTRACT

BACKGROUND: Human amniotic mesenchymal stem cells (hAMSCs) are adult stem cells with multipotential differentiation, which can be induced to differentiate into bone, cartilage and other connective tissues. Meanwhile, as a highly specific marker of tenocytes, Scleraxis is involved in aggregation and differentiation of tendon progenitor cells as well as the formation of tendon extracellular matrix. OBJECTIVE: To investigate whether hAMSCs have the ability of differentiation into tenocytes by ectopic expression of Scleraxis. METHODS: Agreed by puerpera, the amniotic membrane from the full-term placenta was separated, and hAMSCs were isolated by a two-step enzyme digestion, observed under inverted phase contrast microscope, and identified by flow cytometry. Passage 3 cells were induced via plasmid-mediated Scleraxis overexpression in overexpression group. Untransfected cells cultured in normal medium served as blank control group, and those with empty plasmid transfection were defined as empty plasmid group. Cell proliferation was tested in each group using cell counting kit-8 within 7 days of culture. Real-time quantitative PCR and western blot were used to assess the tenogenic differentiation of hAMSCs in each group at 3 and 7 days of culture. RESULTS AND CONCLUSION: Findings from the cell counting kit-8 indicated that the cell viability had no significant differences among the groups within 7 days of culture (P > 0.05). Western blot results showed the protein expression of Scleraxis in the treatment group was significantly higher than that in the other two groups (P < 0.05). Real-time PCR results showed, at 3 days of culture, the expression of collagen type I, collagen type III, Fibronectin and Tenascin-C in the overexpression group was significantly higher than that in the empty plasmid group (P < 0.05), but the expression of Tenomodulin had no difference (P > 0.05); at 7 days of culture, the expressions of collagen type I, collagen type III, Fibronectin, Tenascin-C and Tenomodulin in the overexpression group were significantly higher than those in the empty plasmid group (P < 0.05). In summary, hAMSCs can be differentiated into tenocytes by ectopic expression of Scleraxis.

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