Significant Histologic Changes Are Not Rare in Treatment-naive Hepatitis B Patients with Normal Alanine Aminotransferase Level:A Meta-analysis

Background and Aims:Chronic hepatitis B is the main cause of liver cancer.However,the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase(ALT).People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment.However,the truth is not as optimistic as we thought.We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients.Methods:Medline,Embase,and Cochrane Library were searched up to January 10th 2020,to identify studies of these patients with liver biopsy.The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis.Potential heterogeneity was explored by subgroup analysis and meta-regression.Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis.The secondary outcome was to find the risk factors of significant histological changes.Results:Nineteen eligible studies,with 2,771 participants,were included.The pooled proportion of significant inflammation or fibrosis was 35%[95%confidence interval(CI):27 to 43]and 30%(95%CI:25 to 36),respectively.The pooled proportion of cirrhosis was 3%[95%CI:1 to 5,(12 studies;1,755 participants)].In subgroup analysis,old age[vs.young(<40 years-old),44%vs.26%,p=0.012]was significantly associated with higher fibrosis stage as well as cirrhosis[vs.young(<40 years-old),4.8%vs.1.8%,p<0.001].Conclusions:About 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes,and some even have cirrhosis.

Caerulin-induced pancreatitis in rats: Histological and genetic expression changes from acute phase to recuperation

AIM： To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats. METHODS： Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histological and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema （E）, polymorphonuclear neutrophU （pIVlN） infiltration, cytoplasmic vacuolization （V）, zymogen granule depletion （ZD） and acinar disorganization （AD） were microscopically evaluated. Accumulation of pancreatitis- associated protein （PAP） and L13A mRNAs were quantified by real-time PCR. RESULTS： The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d. CONCLUSION： From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pan- creas occur and PAP expression is exclusively an acute response of pancreatitis.

Time-dependent effects of castration on the bladder function and histological changes in the bladder and blood vessels

We examined the effect of androgens on bladder blood flow （BBF）, bladder function and histological changes in castrated male rats. Male Wistar rats were classified into unoperated group （control group）, groups castrated at the age of 8weeks （group 8wPC） and groups castrated at the age of 4weeks （group 4wPC）. Each rat was used at the age of 20weeks. BBF was measured using fluorescent microspheres. Bladder cystometry was performed without anesthesia or restraint; the bladder was first irrigated with saline and then with 0.25% acetic acid （AA） solution. Maximum voiding pressure and voiding interval were measured. The bladder and lilac artery were histologically examined for differences in smooth muscle and quantity of collagen fiber to analyze the effect of castration on the smooth muscle content. No differences were noted in BBF following castration. The voiding intervals for all groups were shortened （P 〈 0.001） following AA irrigation. No significant difference was noted in the maximum voiding pressure. Histological changes were observed in bladder and lilac artery. Smooth muscle/collagen ratio at the bladder was lower in groups 8wPC and 4wPC compared to the control group （P 〈 0.01）, while that at the lilac artery was decreased in group 4wPC compared to the control group （P〈 0.001）. In conclusion, our findings indicate that castration does not alter BBF, but leads to histological changes in the bladder as well as its associated blood vessels.

Effect of Zinc Sulfate against the Red Palm Weevil Rhynchophorus ferrugineus with Reference to Their Histological Changes on the Larval Midgut and Adult Reproductive System

The red palm weevil Rhynchophorusferrugineus is the most important insect pest for the date palm trees in the Middle East and Gulf states. Zinc sulfate （ZnSOa＇H20） was toxicologically, biologically and physiologically evaluated as insect development disruptors against the RPW. LCs0 of Zinc sulfate against 10 days old larvae was 0.566%, 3% concentration inhibited the larvae from feeding. LCs0 concentration of zinc sulfate solution was capable to disrupting growth, development and reproduction of R. ferrugineus. Growth and development disruptions are resulted from larval feeding on the treated diet that causing percentage of mortality rate, retardation in larval and pupal duration, percentage of pupation, adults emergence, reduction in deposited eggs that laid by the resulting adults and in the egg fertility. The study further reveals that Zinc sulfate effects on histological structure of epithelial cells of the larval midgut including separation and elongation of their cells, rupture in the peritrophic membrane and in some microvilli and some degeneration of the surrounding muscles. Histological changes also was observed on the adults ovary, in this way, disrupt female gamete production through their action on the accumulation of yolk granules （vitellogenesis） and follicular epithelial cells. Disruption of male gamete production was detected by disorganized of testicular cysts and depopulation of these cysts in addition to degeneration in germ cells. Zinc sulfate may be used among other control methods by injection into the tree trunk or as fertilizer around the tree roots which in turn may have an indirect effect for controlling the RPW.

Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer

AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.

Assessment of hindlimb motor recovery affer severe thoracic spinal cord injury in rats: classification of CatWalk XT■ gait analysis parameters

Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT■gait analysis for evaluating hindlimb functional recovery in a widely used and clinically relevant thoracic contusion/compression spinal cord injury model in rats. Rats were randomly assigned to either a T9 spinal cord injury or sham laminectomy. Locomotion recovery was assessed using the Basso, Beattie, and Bresnahan open field rating scale and the CatWalk XT■gait analysis. To determine the potential bias from weight changes, corrected hindlimb(H) values(divided by the unaffected forelimb(F) values) were calculated. Six weeks after injury, cyst formation, astrogliosis, and the deposition of chondroitin sulfate glycosaminoglycans were assessed by immunohistochemistry staining. Compared with the baseline, a significant spontaneous recovery could be observed in the CatWalk XT■parameters max intensity, mean intensity, max intensity at%, and max contact mean intensity from 4 weeks after injury onwards. Of note, corrected values(H/F) of CatWalk XT■parameters showed a significantly less vulnerability to the weight changes than absolute values, specifically in static parameters. The corrected CatWalk XT■parameters were positively correlated with the Basso, Beattie, and Bresnahan rating scale scores, cyst formation, the immunointensity of astrogliosis and chondroitin sulfate glycosaminoglycan deposition. The CatWalk XT■gait analysis and especially its static parameters, therefore, seem to be highly useful in assessing spontaneous recovery of hindlimb function after severe thoracic spinal cord injury. Because many CatWalk XT■parameters of the hindlimbs seem to be affected by body weight changes, using their corrected values might be a valuable option to improve this dependency.

Treatment of Epilepsy with Bipolar Electro-coagulation： An Analysis of Cortical Blood Flow and Histological Change in Temporal Lobe

Background：Bipolar electro-coagulation has a reported efficacy in treating epilepsy involving functional cortex by pure electro-coagulation or combination with resection.However,the mechanisms of bipolar electro-coagulation are not completely known.We studied the acute cortical blood flow and histological changes after bipolar electro-coagulation in 24 patients with intractable temporal lobe epilepsy.Methods：Twenty-four patients were consecutively enrolled,and divided into three groups according to the date of admission.The regional cortical blood flow （rCBF）,electrocorticography,the depth of cortex damage,and acute histological changes （H and E staining,neuronal staining and neurofilament （NF） staining） were analyzed before and after the operation.The t-test analysis was used to compare the rCBF before and after the operation.Results：The rCBF after coagulation was significantly reduced （P 〈 0.05）.The spikes were significantly reduced after electro-coagulation.For the temporal cortex,the depth of cortical damage with output power of 2-9 W after electro-coagulation was 0.34 ± 0.03,0.48 ± 0.06,0.69 ± 0.06,0.84 ± 0.09,0.98 ± 0.08,1.10 ± 0.1 l,1.11 ± 0.09,and 1.22 ± 0.11 mm,respectively.Coagulation with output power of 4-5 W completely damaged the neurons and NF protein in the molecular layer,external granular layer,and external pyramidal layer.Conclusions：The electro-coagulation not only destroyed the neurons and NF protein,but also reduced the rCBF.We concluded that the injuries caused by electro-coagulation would prevent horizontal synchronization and spread of epileptic discharges,and partially destroy the epileptic focus.

Inhibitory Effect of Estrogens,Phytoestrogens,and Caloric Restriction on Oxidative Stress and Hepato-toxicity in Aged Rats

Objective To investigate the protective effect of 17β-estradiol （E2）, peganum harmala extract （PHE） administration and calorie restriction （CR） treatment （60%） on oxidative stress and hepato-toxicity in aged rats. Methods Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups： normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group. Results Aging significantly decreased superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX）, and increased lactate deshydrogenase （LDH）, gamma-glyiamyl transferase （GGT）, pbosphatase alkalines （PAL）, aspartate and lactate transaminase （AST and ALT） activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17β-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats. Conclusion The antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.

Quantitative Histological Study on Changes of the Cortical Bones after Internal Fixation with Plates of Different Rigidity

In an effect to explore the potemtial role of bone microcirculation causing plate-induced reginal osteoporosis

CARDIAC FUNCTION AND HISTOLOGICAL CHANGES AFTER NON-DYNAMIC CARDIOMYOPLASTY AND PRELIMINARY STUDY OF DYNAMIC CARDIOMYOPLASTY

By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4% ?11.7% in GroupⅠ (3 weeks after operation), and 78.4+ 11.6% in Group Ⅱ (3 months after operation). There were muscular atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P<0.05), but the difference between two groups was non?significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-esistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.

Effects of different concentrations of dexamethasone on pulmonary histology in rats with chronic asthma

Objective:To observe the intervention effects of different concentrations of dexamethasone on the general situation and pulmonary histology of chronic asthma rats,and to explore the suitable intragastric dose of dexamethasone in the rat model of chronic asthma.Methods:75 healthy male Sprague-Dawley(SD)rats were randomly divided into normal group,M group,dexamethasone low dose,middle dose and high dose group by random number table.The rat model of chronic asthma was established by sensitization and challenge of ovalbumin(OVA).From the 20th day of the experiment,dexamethasone groups were given intragastric administration of 0.0625mg/(kg·d),0.125mg/(kg·d)and 0.5mg/(kg·d),respectively.The general situation of rats was observed and recorded.The histological changes of rat lungs were observed by HE staining and Masson staining.Results:The degree of inflammatory infiltration of bronchus and surrounding tissue in the M group was significantly higher than that in the normal group(P<0.01).The thickness of airway wall and smooth muscle and the deposition of airway collagen in the M group were significantly higher than those in the normal group(P<0.01).After one week of intervention,the average daily food intake and body mass of rats in the high dose group were significantly lower than those in the M group(P<0.01),and the increase in body mass in the middle and low dose groups was significantly slower than that in the M group(P<0.01).After 2 weeks of intervention,the average daily food intake of rats in the middle and low dose groups was significantly lower than that in the M group(P<0.01).After 4 weeks of intervention,the average daily food intake in the middle and low dose groups was significantly lower than that in the low dose group(P<0.01).The inflammatory infiltration of lung tissue in the middle and low dose groups was significantly less than that in the model group,and the thickness of airway wall and smooth muscle and the deposition of airway collagen in the middle and low dose groups were significantly lower than those in the model group(P<0.01).There was no difference between the two groups(P>0.05).A large number of rats in the high dose group died after 5 times of intervention.Three rats died in the DEXM group at the 5th week of intervention,and there was no death in the other group.Conclusion:Both middle and low doses of dexamethasone can be used as the positive control dose in the experiment of chronic asthmatic rats,but the late side effects of low dose of dexamethasone are less,so the low dose of dexamethasone may be a safer and more suitable dose for the experiment of chronic asthmatic rats.