Objective:To observe the protein and mRNA expressions of microtubule-associated protein 1 light chain 3 (LC3)B, P62 and Beclin1 in the liver of rats with chronic fluorosis, and to explore the role of autophagy in pathogenesis of liver injury induced by fluorosis.Methods:Using a group design, 54 SD rats were divided into 9 groups according to their weight (100 - 120 g) using a random number table method, each group with 6 rats, half male and half female. They were control group (NC group), low fluoride group (LF group), high fluoride group (HF group), NC + rapamycin (RAP) group, LF + RAP group, HF + RAP group, NC + chloroquine (CQ) group, LF + CQ group, and HF + CQ group. The NC group drank tap water (fluoride concentration was 0.5 mg/L), LF group drank fluoride water (fluoride concentration was 5.0 mg/L), HF group drank fluoride water (fluoride concentration was 50.0 mg/L); NC + RAP group, LF + RAP group and HF + RAP group were fed with corresponding drinking water, respectively, for 3 months, and then RAP (1.5 mg/kg) was intraperitoneally administered for 10 d; NC + CQ group, LF + CQ group and HF + CQ group were fed with corresponding drinking water, respectively, for 3 months, and then CQ (60 mg/kg) was intraperitoneally administered for 10 d. Bone and 24-hour urine samples of rats in each group were collected to detect the contents of bone fluoride and urine fluoride; liver histomorphological changes were observed through hematoxylineosin staining; protein and mRNA expressions of LC3B, P62 and Beclin1 in liver were detected by immunohistochemistry and real-time fluorescence quantitative PCR, respectively.Results:Compared with the NC group [(0.03 ± 0.00) mg/kg, (0.34 ± 0.08) mg/L], the contents of bone fluoride [(3.86 ± 0.08) mg/kg] and urine fluoride [(1.11 ± 0.16) mg/L] in HF group were higher ( P < 0.05). In the NC group, the lobule structure of liver tissue was clear, the hepatic cords were arranged in order, and the cell structure was normal. There were different degrees of hepatocyte edema in LF and HF groups. After intraperitoneal injection of RAP, compared with the corresponding fluoride group, the morphology of hepatocytes did not change significantly. After intraperitoneal injection of CQ, compared with the corresponding fluoride group, the liver cells showed obvious edema, and the degree of edema aggravated with the increase of fluoride concentration. Compared with the NC group, the protein expressions of LC3B and Beclin1 in HF group were higher ( P < 0.05), and the protein expression of P62 was lower ( P < 0.05). After intraperitoneal injection of RAP, the protein expressions of LC3B and P62 in LF + RAP group was lower than that in LF group ( P < 0.05); Compared with HF group, the protein expressions of LC3B and Beclin1 in HF + RAP group were lower ( P < 0.05). After intraperitoneal injection of CQ, protein expression of P62 in LF + CQ group was higher than that in LF group ( P < 0.05); Compared with HF group, protein expression of P62 in HF + CQ group was higher ( P < 0.05). Conclusions:Early (3 month) fluoride intake could promote autophagy and induce edema of hepatocytes in rats, and RAP had similar effects. CQ may induce liver injury by inhibiting autophagy of hepatocytes.

Objective To determine if using a soft-tipped guidewire to cannulate the common bile duct may ameliorate development of PEP(post-ERCP pancreatitis)and facilitate cannulation of the CBD(common bile duct).Methods A total of 78 patients treated treateed in our hospital underwent ERCP through conventional direct cannulation(52 diagnostic ERCPs,26 therapeutics ERCPs)from 1998 to 2001 were randomly selected as group A while 112 patients underwent ERCP through guide wire-directed cannulation(21 diagnostic ERCPs,91 therapeutics ERCPs)from 2007 to 2008 as group B.Then we retrospectively studied and compared the following parameters between the two groups:1)Success rate of biliary access;2)visualization rate of pancreatic duct;3)the level of serum amylase,severity of abdominal pain and the rate of PEP.Meanwhile,the correlation between grading of pancreatic duct visualization and PEP was analyzed.Results The success rate of biliary access of the guidewire group(106/112 cases)was significantly greater than the conventional group(33/78 cases)(94.64%vs.42.30%,P<0.01).In group A,about61.53%(16/26)of the 26 cases could not continue the next therapeutics ERCP because of unsucceasful carmulation. The visualization rate of pancreatic duct of group A and B were 58.97%(46/78 cases)and 8.04%(9/112 cases)(P<0.01) respectively.On occurrence rate of PEP,group A(17/78 cases)was significantly higher than group B(4/112 cases)(21.79% vs.3.57%,P<0.01),and severe pancreatitis occurred in 3 patients in conventional group.However,there was no severe pancreatitis in the guide wire group.There were no significant differences (P>0.05) in terms of the rate of hyperamylasemia between the two groups.The significant correlation was found between the grading of pancreatic duct visualization and the occurrence of PEP.Condusion Guidewire-directed selective access to the bile duct lowers likdihood of PEP by facilitating cannulation and lowering the visualization rate of pancreatic duct.The occurrence of PEP could be predicted by the grading of pancreatic duct visualization,which is a very important but not the unique factor leading to PEP.

Objective To evaluate the effect of early non-liquid diet for patients with mild acute pancreatitis by using Meta-analysis. Methods The randomized controlled trials(RCT) on early non-liquid diet intake for patients with mild acute pancreatitis were collected by computer searching the database of China National Knowledge Infrastructure(CNKI),Wanfang Periodical Database,CBM,Elsevier Scien Direct, cochrane library and PubMed from inception to February 2017, and analyzed by RevMan 5.2 software. Results Five RCTs were included in the study.The Results of Meta-analysis revealed that both the length of hospitalization after eating [MD=-1.48,95%CI-2.50~-0.47, P=0.004] and the total length of hospitalization[MD=-1.99,95%CI-(0.99-2.99),P=0.0001]in liquid diet group were less than that of non-liquid diet group,and the differences were statistically significant.There was no significant difference in the rate of the pain recurrence[RR=1.21,95%CI 0.77-1.91,P=0.40]and the rate of the elimination of oral feeding[RR=1.02,95%CI 0.45-2.30,P=0.96]because of pain,nausea or vomiting after refeeding,although all that rate in non-liquid diet was not lower than that of liquid diet group. Conclusions compared with liquid diet,early non-liquid diet intake for mild acute pancreatitis can shorten their hospitalization time, and it cannot be concluded that the non-liquid diet will increase the pain recurrence rate, and most patients have a better tolerance to non-liquid diet,and non-liquid diet can promote rehabilitation.

OBJECTIVETo investigate the potential role of preoperative adjuvant chemotherapy on early stage cervical squamous carcinoma with bulky tumor.

METHODSOne hundred and forty-five patients with cervical squamous cancer stages Ib-IIa were investigated, among which 17 patients with bulky tumors (> or = 4 cm) were managed by cisplatin-based chemotherapy for 1-2 courses followed by radical hysterectomy and pelvic lymphadenectomy (BC group). The change of tumor size, pelvic lymph nodes metastasis, cervical wall invasion, the involvement of surgical specimen margin, and the blood loss during operation were assessed after operation and compared with those in 51 patients with bulky tumors (BN group) and 77 patients with small local tumors (S group) who underwent surgery directly.

RESULTS(1) The tumor size of 17 patients in BC group were decreased in various degrees after chemotherapy, with 13 patients of clinical effectiveness (76.47%). And the responsiveness pertained to neither histological differentiation nor size of local tumors. (2) Post-operative histology has showed that patients in BC and BN group have higher incidence of lymph node metastasis and deep cervical infiltration (5/68 and 3/68, respectively) than in S group (1/77 and 1/77, respectively) while with no statistical significance. (3) Blood loss during operation in BC group was less than BN and S group. (4) Seventeen patients, including those underwent surgeries of vaginal prolongation and/or ovarian transposition, appeared disease-free survival within the follow-up time.

CONCLUSIONSMost of patients with bulky early stage cervical squamous carcinoma are sensitive to cisplatin-based chemotherapy, which could greatly reduce local tumor size and in turn facilitate the following operation by well controlling blood loss.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; administration & dosage ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; secondary ; surgery ; Chemotherapy, Adjuvant ; Cisplatin ; administration & dosage ; Drug Administration Schedule ; Etoposide ; administration & dosage ; Female ; Humans ; Hysterectomy ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Preoperative Care ; Uterine Cervical Neoplasms ; drug therapy ; pathology ; surgery ; Vincristine ; administration & dosage

Endoscopy, Digestive System ; Esophageal and Gastric Varices ; complications ; drug therapy ; surgery ; therapy ; Fibrosis ; complications ; Gastrointestinal Hemorrhage ; drug therapy ; etiology ; surgery ; therapy ; Humans ; Hypertension, Portal ; drug therapy ; etiology ; surgery ; therapy

Objective:To explore whether chronic fluorosis can cause liver fibrosis in rats by observing expression changes in type Ⅰcollagen (Col-Ⅰ), type Ⅲ collagen (Col-Ⅲ) and alpha smooth actin (α-SMA) in the liver tissue of chronic fluorosis rats.Methods:According to body weight (90 - 100 g), forty-eight SD rats were randomly divided into control group (drinking water fluoride ion concentration < 0.5 mg/L), low, medium and high concentration fluoride groups (drinking water fluoride ion concentration of 5.0, 50.0 and 100.0 mg/L), with 12 rats in each group (half male and half female), and fed for 6 months. Fluoride ion selective electrode method was used to detect bone fluoride and urinary fluoride levels; hematoxylin-eosin staining (HE staining) and Masson staining were used to observe the pathological and morphological changes and the collagen deposition of liver tissue; quantitative real-time polymerase chain reaction and immunohistochemical staining were used to observe Col-Ⅰ, Col-Ⅲ and α-SMA mRNA and protein expressions.Results:There was significant difference in bone fluoride and urine fluoride between the 4 groups [bone fluoride: (92.52 ± 5.64), (112.21 ± 11.86), (142.99 ± 7.87), (235.63 ± 11.55) mg/kg; urinary fluoride: (5.47 ± 0.88), (17.78 ± 1.48), (54.16 ± 5.96), (121.11 ± 6.32) mg/L, P < 0.001]. Under light microscope, with the increase of fluoride concentration, the degree of hepatic cell edema was aggravated, and the deposition of collagen fiber around the central vein and the portal area increased significantly. The mRNA expression level of Col-Ⅰ in low, medium and high concentration fluoride groups (1.20 ± 0.09, 1.80 ± 0.08, 1.58 ± 0.06) was significantly higher than that in control group (1.00 ± 0.00, P < 0.05); Col-Ⅲ and α-SMA mRNA expression levels in medium and high concentration fluoride groups (Col-Ⅲ: 1.15 ± 0.14, 1.64 ± 0.24; α-SMA: 1.69 ± 0.02, 2.34 ± 0.06) were significantly higher than those of low concentration fluoride group (Col-Ⅲ: 0.59 ± 0.17; α-SMA: 0.80 ± 0.13, P < 0.05). With the increase of fluoride concentration, the liver tissue Col-Ⅰ(0.00 ± 0.00, 0.03 ± 0.01, 0.08 ± 0.01, 0.13 ± 0.02), Col-Ⅲ (17 803.05 ± 3 221.16, 47 523.15 ± 3 490.10, 127 786.35 ± 13 008.86, 237 233.03 ± 47 614.63) and α-SMA (516.83 ± 181.18, 2 885.03 ± 864.92, 11 186.94 ± 2 394.08, 37 182.43 ± 12 390.59) protein levels were also increased significantly ( P < 0.05). Conclusion:Long-term excessive intake of fluorine may cause the production of collagen fibers around the central vein and the portal area of the liver in rats to increase, and then lead to the formation of liver fibrosis.

A proportion of patients experience acute or even prolonged cognitive impairment after surgery, a condition known as postoperative cognitive dysfunction (POCD). It is characterized by impairment in different cognitive domains and neuroinflammation has been implicated as one of the inciting factors as strategies targeting inflammation tend to improve cognitive performance. Siegesbeckia Orientails L. (S. Orientails) is a common Chinese medicinal herb used for managing chronic inflammatory diseases. We investigated if pretreatment with S. Orientails before surgery confers any neuroprotective effects in postoperative animals in terms of reducing inflammation and mitigating cognitive impairment. Three-month-old male C57BL/6N mice were fed different doses of S. Orientails extract for 14 days before they underwent a laparotomy. After cognitive testing they were sacrificed on postoperative day (POD) 3. Our results showed that animals with extract pretreatment demonstrated memory improvement in a dose-dependent manner compared with control. Further, evidence for the attenuation of systemic and neuroinflammation was found in the pretreated animals, along with the inhibition of inflammatory pathways and significantly reduced tau phosphorylation in the hippocampus. Taken together, these results demonstrated a neuroprotective effect of S. Orientails in postoperative animals, indicating a therapeutic potential of S. Orientails in minimizing POCD and the possibility of utilizing this traditional Chinese medicine perioperatively.
Animals ; Asian Continental Ancestry Group ; Cognition Disorders ; Hippocampus ; Humans ; Inflammation* ; Laparotomy ; Male ; Medicine, Chinese Traditional ; Memory ; Mice ; Neuroprotective Agents ; Phosphorylation ; Plants, Medicinal

Objective:To investigate the expression changes of Hedgehog related factors (Ihh, Shh and Smo) in bone of rats with chronic fluorosis, and the significance.Methods:Thirty-six healthy SD rats were divided to three groups with the method of random digits table by body weight (100 - 120 g), 12 rats in each group, half male and half female. The rats of control were fed with tap water (NaF < 1 mg/L), and the experimental rats were exposed to NaF (low dose fluoride group: 5 mg/L, high dose fluoride group: 50 mg/L) added to the drinking water to establish the chronic fluorosis model. After the rats were raised for six months, 24-hour urine samples were collected and the femoral metaphysis of the rats was taken. Urine fluoride and bone fluoride were detected by fluorin ion selective electrode method. Bone tissues were stained with hematoxylin-eosin and observed under light microscope. The content of bone alkalinephosphatase (BALP) in rats' serum was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of Ihh, Shh and Smo mRNA and protein in bone were detected by Real-time PCR and immunohistochemistry (IHC).Results:The contents of urine fluoride, bone fluoride and serum BALP were increased gradually in the control, low and high doses fluoride groups [urine fluoride: (1.37 ± 0.44), (5.96 ± 0.56), (7.60 ± 0.61) mg/L; bone fluoride: (306.04 ± 12.58), (652.91 ± 51.83), (1 094.11 ± 126.34) mg/kg; BALP: (27.78 ± 4.09), (46.59 ± 5.75), (57.45 ± 3.99) U/L, P < 0.05]. It could observed that bone sclerosis by light microscope in low and high doses fluoride groups. The expressions of Ihh, Shh and Smo mRNA in high dose fluoride group (1.39 ± 0.36, 0.56 ± 0.23, 0.40 ± 0.15) were higher than those of the control and low dose fluoride groups (0.73 ± 0.19, 0.92 ± 0.34; 0.19 ± 0.04, 0.36 ± 0.16; 0.14 ± 0.04, 0.24 ± 0.13; P < 0.05). The expression of Shh mRNA in low dose fluoride group was higher than that of the control group ( P < 0.05). The expressions of Ihh and Smo protein in high dose fluoride group (138.89 ± 3.72, 149.29 ± 7.63) were higher than those of the control and the low dose fluoride groups (127.39 ± 2.69, 134.81 ± 3.53; 129.64 ± 12.62, 139.07 ± 9.30), and the low dose fluoride group were higher than those of the control group ( P < 0.05). The expression of Shh protein in high dose fluoride group (141.26 ± 7.49) was higher than that of the control group (130.96 ± 11.10, P < 0.05). Conclusion:The expression of Hedgehog signaling pathway related factors in bone of rats with chronic fluorosis is changed, which indicates that bone formation can be affected by activation of Hedgehog signaling pathway induced by fluoride.

Objective:To investigate the MRI differences between locally advanced rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma before and after neoadjuvant chemoradiotherapy (NCR).Methods:A retrospective cohort study was conducted to collect the clinical and imaging data of 165 patients with locally advanced rectal adenocarcinoma treated by NCR combined with surgery from October 2016 to October 2019 in the Sixth Affiliated Hospital of Sun Yat-sen University, 36 cases were rectal mucinous adenocarcinoma and 129 cases were non-mucinous adenocarcinoma. The image features of the two groups before and after NCR were evaluated based on MRI, including the length and thickness of the tumor, the distance from the lower edge of the tumor to the anal edge, T stage, N stage, involvement of mesorectal fascia (MRF) and peritoneal reflux. The difference of NCR and the change of MRI characteristics after NCR were compared by independent sample t test, Mann-Whitney U test or χ 2 test. The accuracy of MRI re-staging after NCR was evaluated according by postoperative pathological staging results. Results:Before NCR, there was significant difference in length of tumor between mucinous adenocarcinoma and non-mucinous adenocarcinoma groups ( P=0.044), there was no significant difference in the distance from the lower edge of the tumor to the anal edge, thickness of the tumor, T stage, N stage, involvement of MRF and peritoneal reflux (all P>0.05). After NCR, in patients with non-mucinous adenocarcinoma, the distance reduction from the lower edge of the tumor to the anal edge, the length reduction of the tumor, the thickness reduction of the tumor, the T-stage decline rate were significantly higher than those in the mucinous adenocarcinoma group (all P<0.05). The N-stage decline rate of mucinous adenocarcinoma was higher than that in non-mucinous adenocarcinoma group ( P=0.008). After NCR, MRI overestimated T staging of patients with both mucinous adenocarcinoma and non-mucinous adenocarcinoma compared with pathological T-stage ( P<0.001). In patients with mucinous adenocarcinoma, MRI overstated the N-stage than pothology ( P=0.001). Conclusions:There is different sensitivity of mucinous adenocarcinoma and non-mucinous adenocarcinoma to NCR. Patients with non-mucinous adenocarcinoma benefit more from the efficacy of NCR. The accuracy of MRI in re-staging of rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma after NCR needs to be improved.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.