Different concentrations of hyaluronic acid eye drops for dry eye syndrome: a systematic review and Meta-analysis

AIM:To compare high or low concentration of hyaluronic acid eye drops(HY)for dry eye syndromes(DES).METHODS:Randomized controlled trials(RCTs)comparing various concentrations of HY were searched in PubMed,Embase,Web of Science,Cochrane,SinoMed,CNKI,Wanfang Database,CQVIP,and Chinese journals databases between inception and July 2023.Pooled standardized mean differences(SMD)or weighted mean difference(WMD)with 95%confidence intervals(CI)from RCTs evaluating Schirmer’s I test(SIT),corneal fluorescein staining score(CFS),tear breakup time(TBUT),DES score(DESS),and Ocular Surface Disease Index(OSDI)were calculated.Sensitivity analysis,Egger’s test and Meta-regression analysis were performed for all indicators.RESULTS:We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria,involving 1796 cases.High-concentrations group significantly improved the outcome of CFS according to random effects modelling(SMD,-3.37;95%CI,-5.25 to-1.48;P=0.0005).The rest of the results were not statistically significant,including indicators such as SIT,TBUT,DESS and OSDI.CONCLUSION:For dry eyes with positive corneal staining,a high concentration of HY is recommended,whereas in other cases,a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

AIM: To investigate if there are changes in serotonin (5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS). METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n = 20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography- electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 ± 90, 122 ± 54, 61 ± 35 ng/mg protein, respectively, which were all lower than those in the normal group (256 ± 84, 188 ± 91, and 93 ± 45 ng/ mg protein, respectively), with a significant difference at the jejunum (P < 0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P < 0.001). (3) The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 ± 9.4 and 35.8 ± 5.5/highpower field (hpf), respectively, which were significantly more than that in the normal group (29.8 ± 4.4/hpf) (P < 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 ± 9.4, 35.8 ± 5.5, 29.8 ± 4.4/hpf, respectively) than at the duodenum (19.6 ± 4.7, 18.5 ± 6.3, 19.2 ± 3.3/hpf, respectively, P < 0.001). CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.

Estrogen reduces CCL_4-induced liver fibrosis in rats

AIM: Chronic liver diseases, such as fibrosis or cirrhosis,are more common in men than in women. This genderdifference may be related to the effects of sex hormones onthe liver. The aim of the present work was to investigatethe effects of estrogen on CCL4-induced fibrosis of the liverin rats.METHODS: Liver fibrosis was induced in male, female andovariectomized rats by CCL4 administration. All the groupswere treated with estradiol(1 mg/kg) twice weekly. Andtamoxifen wasgiven to male fibrosis model. At the end of 8weeks, all therats were killed to study serum indicators andthe livers.RESULTS: Estradiol treatment reduced aspartateaminotransferase(AST), alanine aminotransferase (ALT),hyaluronic acid(HA) and type IV collagen(CIV) in sera,suppressed hepatic collagen content, decreased the areas ofhepatic stellate cells (HSC) positive for α-smooth muscle actin(α-SMA), and lowered the synthesis of hepatic type I collagensignificantly in both sexes and ovariectomy fibrotic rats inducedby CCL4 administration. Whereas, tamoxifen had the oppositeeffect. The fibrotic response of the female liver to CCL4treatment was significantly weaker than that of male liver.CONCLUSION: Estradiol reduces CCL4-induced hepaticfibrosis in rats. The antifibrogenic role of estrogen in theliver may be one reason for the sex associated differencesin the progression from hepatic fibrosis to cirrhosis.

Effects of extract from Ginkgo biloba on carbon tetrachloride-induced liver injury in rats

AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCh and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol （v/v）. EGb-protected group was treated with EGb （0.5 g/kg body weight per day） for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 （TGF-β1） a-smooth muscle actin （α-SMA） and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS： The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and albumin （AIb） in EGb-protected group were notably improved as compared with the CCL4-treated group （P 〈 0.01）. The contents of serum hyaluronic acid （HA）, type III procollagen （PCⅢ）, type IV collagen （CIV） and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups （P 〈 0.05, P 〈 0.01）. The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups （6.58 ±1.25 vs 9.52 ± 2.06, P 〈 0.05）. Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase （Se-GSH-Px）, superoxide dismutase （SOD） and malondialdehyde （MDA） were strikingly improved also in EGb-protected group （P 〈 0.05, P 〈 0.01）. CONCLUSION： EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.

A randomized,double-blind,placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation

AIM： To evaluate the efficacy and safety of tegaserod, 6 mg twice daily （b.i.d.）, in men and women with chronic constipation （CC） from China. METHODS： This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatmentfree baseline period, patients were randomized to receive either tegaserod （6 mg b.i.d.） or placebo （b.i.d.） for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements （CSBMs） during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients＇ daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events （AEs）. RESULTS： A total of 607 patients were randomized to receive either tegaserod （n = 304） or placebo （n = 303）. Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo （1.39 vs 0.91, P = 0.0002）. A statistically significant difference in favor of tegaserod was also observed for a mean increase ≥ 1 CSBM/wk over wk 1-4 （47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018） and for the absolute number of≥ 3 CSBMs/wk over wk 1-4 （25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021）. Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod （3.6%） compared with placebo （1.7%）. CONCLUSION： Tecjaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.

GFAP and Fos immunoreactivity in lumbo-sacral spinal cord and medulla oblongata after chronic colonic inflammation in rats

AIM： To investigate the response of astrocytes and neurons in rat lumbo±sacral spinal cord and medulla oblongata induced by chronic colonic inflammation, and the relationship between them. METHODS： Thirty-three male Sprague-Dawley rats were randomly divided into two groups： experimental group （n = 17）, colonic inflammation was induced by intra-luminal administration of trinitrobenzenesulfonic acid （TNBS）; control group （n = 16）, saline was administered intra-luminally. After 3, 7, 14, and 28 d of administration, the lumbo-sacral spinal cord and medulla oblongata were removed and processed for anti-glial fibrillary acidic protein （GFAP）, Fos and GFAP/Fos immunohistochemistry. RESULTS： Activated astrocytes positive for GFAP were mainly distributed in the superficial laminae （laminae Ⅰ-Ⅱ） of dorsal horn, intermediolateral nucleus （laminae Ⅴ）, posterior commissural nucleus （laminae Ⅹ） and anterolateral nucleus （laminae Ⅸ）. Fos-IR （Fos-immunoreactive） neurons were mainly distributed in the deeper laminae of the spinal cord （laminae Ⅲ-Ⅳ, Ⅴ-Ⅵ）. In the medulla oblongata, both GFAP-IR astrocytes and Fos-IR neurons were mainly distributed in the medullary visceral zone （MVZ）. The density of GFAP in the spinal cord of experimental rats was significantly higher after 3, 7, and 14 d of TNBS administration compared with the controls （50.44±16.8, 29.24±6.5, 24.14±5.6, P〈0.05）. The density of GFAP in MVZ was significantly higher after 3 d of TNBS administration （34.34±2.5, P〈0.05）. After 28 d of TNBS administration, the density of GFAP in the spinal cord and MVZ decreased and became comparable to that of the controls （18.04±4.9, 14.64±6.4, P〉0.05）. CONCLUSION： Astrocytes in spinal cord and medulla oblongata can be activated by colonic inflammation. The activated astrocytes are closely related to Fos-IR neurons. With the recovery of colonic inflammation, the activity ofastrocytes in the spinal cord and medulla oblongata is reduced.

Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues

AIM： To study the molecular forms of trefoil factor 1 （TFF1） in normal gastric mucosa and its expression in normal and abnormal gastric tissues （gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa） and the role of TFF1 in the carcinogenesis and progression of gastric carcinoma and its molecular biological mechanism underlying gastric mucosa protection. METHODS： The molecular forms of TFF1 in normal gastric mucosa were observed by Western blot. The expression of TFF1 in normal and abnormal gastric tissues （gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa） was also assayed by immunohistochemical method. The average positive AO was estimated by Motic Images Advanced 3.0 software. RESULTS： Three patterns of TFF1 were found in normal gastric mucosa： monomer, dimmer, and TFF1 compound whose molecular weight is about 21 kDa. The concentration of TFF1 compound was the highest among these three patterns. TFF1 was expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum, especially around the nuclei. The closer the TFF1 to the lumen, the higher the expression of TFF1, The expression of TFF1 in peripheral tissue of gastric carcinoma （0.51 ± 0.07） was higher than that in normal gastric mucosa （0.44 ± 0.06, P 〈 0.001）. The expression of TFF1 in gastric adenocarcinoma was positively related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma was, the weaker the expression of TFF1. No TFF1 was expressed in poorlydifferentiated adenocarcinoma. The expression of TFF1 in moderately-well differentiated adenocarcinoma （0.45 ± 0.07） was a little lower than that in normal mucosa （P 〉 0.05）. The expression of TFF1 in gastric mucosa with atypical hyperplasia （0.57 ± 0.03） was significantly higher than that in normal gastric mucosa （P 〈 0.001）. No TFF1 was expressed in intestinalized gastric mucosa. There was no statistically significant difference between the expressions of TFFI in gastric mucosa around the intestinalized tissue （0.45 ± 0.07） and normal gastric mucosa （P 〉 0.05）. CONCLUSION： TFF1 is expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum. Its main pattern is TFF1 compound, which may have a greater biological activity than monomer and dimer. The expression of TFF1 in peripheral mucosa of gastric ulcer is higher than that in mucosa 5 cm beyond the ulcer, indicating that TFF1 plays an important part in protection and restitution of gastric mucosa. The expression of TFF1 is increased in peripheral tissues of gastric carcinoma and gastric mucosa with atypical hyperplasia, but is decreased in cancer tissues, implying that TFF1 may be related to suppression and differentiation of carcinoma. The weaker expression of TFF1 in poorly-differentiated carcinoma may be related to the destruction of glands and cells in cancer tissues and the decrease in secretion of TFF1.

Relationship between entero-hepatic bile acid circulation and interdigestive migrating myoelectrical activity in rats

AIM： To investigate the effects of entero-hepatic bile add circulation on the inter-digestive migrating myoelectrical complex （MMC） in rats. METHODS： Thirty-two rats were divided into four groups. Three pairs of bipolar silver electrodes were chronically implanted in the antrum, duodenum and jejunum. Three groups of Uhem were ligatecl around the upper part of common bile duct （CBD）. The experiments were performed in consdous and fasting state. The gastrointestinal myoelectrical activity was recorded. Ursodeoxycholic acid （UDCA） and saline were then perfused into stomachs of two groups with CBD obstruction and the effects of them on the MMC were observed. RESULTS： A typical pattern of MMC was observed in normal fasting rats. MMC of antral and duodenal origin disappeared temporarily in earlier stage of CBD obstruction. While MMC of jejunum origin appeared. increased MMC cycle duration was seen after 4 d in rats with CBD obstruction. The MMC after CBD obstruction was characterized by an increased duration of phase Ⅱ-like activity and decreased duration of phase Ⅰ ＆ Ⅲ activity. Perfusion into stomachs with UDCA resulted in a shorter MMC cycle duration and a longer duration of phase III of duodenal origin compared to the normal group. CONCLUSION： Entero-hepatic bile add drculation initiates inter-digestive MMC of duodenal origin.

Construction of prokaryotic expression system of TGF-β1 epitope gene and identification of recombinant fusion protein immunity

AIM： To insert the constructed TGF-β1 epitope gene into the el loop of C-terminus of truncated hepatitis B core antigen to increase TGF-β1 antigenicity in its prokaryotic expression system and to identify immunity of the expressed recombinant protein in order to exploit the possibility for obtaining anti- TGF-β1 vaccine. METHODS： The TGF-β1 encoding epitope gene （the mature TGF-β1 from 78-109 amino acid residues, TGF-β1^32） was amplified by polymerase chain reaction from the recombinant pGEM-7z/ TGF-β1 ^32 vector. The HBcAg gene fragments （encoding HBcAg from 1-71 and 89-144 amino acid residues） were amplified from PYTAI- HBcAg vector. The recombinant vector pGEMEX-1 was used to insert HBcAg1-71, TGF-β1^32 and HBcAg89-144 into restrictive endonuclease enzyme and ligated with T4 Ugase. The fusion gene fragments HBc.Ag1-71-TGF-β1^32 HBcAg89-144 were recloned to pET28a（＋） and the DNA sequence was confirmed by the dideoxy chain termination method. The recombinant vector pET28a （＋）/ CTC was transformed and expressed in E. coli BL21 （DE3） under induction of IPTG. After purification with Ni^＋2 NTA agarose resins, the antigenicity of purified protein was detected by ELISA and Western blot and visualized under electron microscope. RESULTS： Enzyme digestion analysis and sequencing showed that TGF-β1 epitope gene was inserted into the el loop of C-terminus of truncated hepatitis B core antigen. SDS-PAGE analysis showed that relative molecular mass （Mr） of the expressed product by pET28a （＋）/CTC was Mr 24 600.The output of the target recombinant protein was approximately 34.8% of the total bacterial protein,mainly presented in the form of inclusion body. Western blotting and ELISA demonstrated that the fusion protein could combine with anti-TGF-β1 polyclonal IgG but not with anti-HBcAg. The purity of protein was about 90 % and the protein was in the form of self-assembling particles visualized under electron microscope. This fusion protein had good anti-TGF-β1 antigenicity and could be used as anti-TGF-β1 vaccine. CONCLUSION： A recombinant prokaryotic expression system with high expression efficiency of the target TGF-β1 epitope gene was successfully established. The fusion protein is in the form of self-assembling particles and HBcAg can increase the antigenicity of TGF-β1. The expressed TGF-β1 epitope gene shows good immunogenicity and antigenicity.

Incidence of gastroesophageal reflux disease in Uygur and Han Chinese adults in Urumqi

AIM:To investigate the incidence of gastroesophageal reflux disease(GERD) and its related risk factors in Uygur and Han Chinese adult in Urumqi,China.METHODS:A population-based cross-sectional survey was undertaken in a total of 972 Uygur(684 male and 288 female) aged from 24 to 61 and 1023 Han Chinese(752 male and 271 female) aged from 23 to 63 years.All participants were recruited from the residents who visited hospital for health examination from November 2011 to May 2012.Each participant signed an informed consent and completed a GERD questionnaire(GerdQ) and a lifestyle-food frequency questionnaire survey.Participants whose Gerd Q score was ≥ 8 and met one of the following requirements would be enrolled into this research:(1) being diagnosed with erosive esophagitis(EE) or Barrett's esophagus(BE) by endoscopy;(2) negative manifestation under endoscopy(non-erosive reflux disease,NERD) with abnormal acid reflux revealed by 24-h esophageal pH monitoring;and(3) suffering from typical heartburn and regurgitation with positive result of proton pump inhibitor test.RESULTS:According to Gerd Q scoring criteria,340 cases of Uygur and 286 cases of Han Chinese were defined as GERD.GERD incidence in Uygur was significantly higher than in Han Chinese(35% vs 28%,χ2 = 11.09,P < 0.005),Gerd Q score in Uygur was higher than in Han Chinese(7.85 ± 3.1 vs 7.15 ± 2.9,P < 0.005),and Gerd Q total score in Uygur male was higher than in female(8.15 ± 2.8 vs 6.85 ± 2.5,P < 0.005).According to normalized methods,304(31%) cases of Uygur were diagnosed with GERD,including 89 cases of EE,185 cases of NERD and 30 cases of BE;256(25%) cases of Han Chinese were diagnosed with GERD,including 90 cases of EE,140 cases of NERD and 26 cases of BE.GERD incidence in Uygur was significantly higher than in Han Chinese(31% vs 25%,χ2 = 9.34,P < 0.005) while the incidences were higher in males of both groups than in females(26% vs 5% in Uygur,χ2 = 35.95,P < 0.005,and 19.8% vs 5.2% in Han,χ2 = 5.48,P < 0.025).GERD incidence in Uygur male was higher than in Han Chinese male(26% vs 19.8%,χ2 = 16.51,P < 0.005),and incidence of NERD in Uygur was higher than in Han Chinese(χ2 = 10.06,P < 0.005).Occupation(r = 0.623),gender(r = 0.839),smoking(r = 0.322),strong tea(r = 0.658),alcohol drinking(r = 0.696),meat-based diet(mainly meat)(r = 0.676) and body mass index(BMI)(r = 0.567) were linearly correlated with GERD in Uygur(r = 0.833,P = 0.000);while gender(r = 0.957),age(r = 0.016),occupation(r = 0.482),strong tea(r = 1.124),alcohol drinking(r = 0.558),meat diet(r = 0.591) and BMI(r = 0.246) were linearly correlated with GERD in Han Chinese(r = 0.786,P = 0.01).There was no significant difference between Gerd Q scoring and three normalized methods for the diagnosis of GERD.CONCLUSION:GERD is highly prevalent in adult in Urumqi,especially in Uygur.Male,civil servant,smoking,strong tea,alcohol drinking,meat diet and BMI are risk factors correlated to GERD.

Possible Role of Mast Cells and Neuropeptides in the Recovery Process of Dextran Sulfate Sodium-induced Colitis in Rats

Objective To clarify the role of mast cells and neuropeptides substance P （SP）, somatostatin （SS）, and vasoactive intestinal peptide （VIP） in dextran sulfate sodium （DSS）-induced colitis in rats. Methods Experimental colitis was induced in Sprague-Dawley rats （180-200 g, n=20） by oral in- gestion of 4% （w/v） DSS in drinking water for 7 days. Control rats （n=5） drank water and were sacrificed on day 0. Mast cell number, histamine levels in whole blood and tissue, tissue levels of SP, SS and, VIP in the dis- tal colon of the rats were measured on day 8, day 13, and day 18 of experimentation. Results Oral administration of 4% DSS solution for 7 days resulted in surface epithelial loss and crypt loss in the distal colon. Mast cell count increased on day 8 （1.75±1.09/mm vs. 0.38±0.24/mm, P〈0.05） and day 13 （1.55±1.01/mm vs. 0.38±0.24/mm, P〈0.05） after DSS treatment. Whole blood his- tamine levels were increased on day 8 （266.93±35.62 ng/mL vs. 76.87±32.28 ng/mL, P〈0.01） and gradu- ally decreased by clay 13 and day 18 after DSS treatment. Histamine levels in the distal colon were decreased on day 8 （1.77±0.65 ng/mg vs. 3.06±0.87 ng/mg, P〈0.05） and recovered to control levels by day 13 after DSS treatment. SP level in the distal colon gradually increased and were raised significantly by day 13 （8777.14±3056.14 pg/mL vs. 4739.66±3299.81 pg/mL, P〈0.05） after DSS treatment. SS and VIP levels in the distal colon were not changed. Conclusions Mast cell degranulation followed by histamine release may play an important role in the pathogenesis of colitis induced by DSS. SP may be a significant substance in the progression of inflamma- tion and the recovery process of DSS-induced colitis.