OBJECTIVE To explore the potential mechanisms of astragalin （AG） in allevating ulcerative colitis （UC） in mice through modulation of the intestinal flora. METHODS Male C57BL/6 mice were randomly divided into normal group （CON group）， model group [dextran sodium sulfate （DSS） group]， 5-aminosalicylic acid group （5-ASA group）， AG low-dose group and high-dose group （AGL and AGH groups）， with 8 mice in each group. The mice UC model was established by drinking 3% DSS solution continuously for 7 days in all groups except the CON group. After that， 3% DSS solution was replaced by water， and the mice of each drug group were gavaged with the corresponding drug solution. Mice in the CON and DSS groups were gavaged with an equal volume of normal saline， once a day， for 7 days. After the last gavage， the body weight change index， disease activity index （DAI） score， colon length and spleen index， and levels of inflammatory factors （tumor necrosis factor-α， interleukin-1β， interleukin-6） were compared among the mice in each group； pathological changes in colonic tissues of the mice were observed in each group， and the pathological score and the percentage of goblet cells were compared； mRNA expressions of barrier-related factors [occludin and ZO-1] and inflammation-related factors [silencing information regulatory factor 1 （SIRT1）， c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK）] were detected in each group of mice； the changes in the intestinal flora of mice in each group were analyzed and the contents of intestinal metabolites short-chain fatty acids （SCFAs） was determined. Using DSS and AG-treated fecal bacterial liquid as an intervention， the mechanism of anti-UC effect of AG was further verified by a fecal microbiota transplant experiment. RESULTS Compared with the CON group， the intestinal mucosal structure of mice in the DSS group was severely damaged， with obvious infiltration of inflammatory cells collapsing the wall； their body weight change index， colon length， the percentage of goblet cells， mRNA expressions of occludin， ZO-1 and SIRT1， Chao1 and Shannon indexes， and contents of acetic acid and butyric acid were significantly reduced， shortened or down-regulated （P＜0.05）； however， DAI score， spleen index， levels of inflammatory factors， pathological score， as well as mRNA expressions of p38 MAPK and JNK， were all significantly increased or up-regulated （P＜0.05）. Compared with the DSS group， colon tissue lesions of AG mice in all dose groups showed different degrees of improvement， and the above quantitative indexes were generally regressed （P＜0.05）， and the intervention effect of AG-treated fecal bacterial fluid was basically the same as that of AG. CONCLUSIONS AG can improve relevant symptoms in UC mice and reduce their inflammatory response and colonic histopathological changes. The above effects may be related to regulating the diversity of intestinal flora in mice， increasing the contents of butyric acid and propionic acid， and promoting the repair of the colonic mucosal barrier， thus regulating the expressions of genes related to the SIRT1/p38 MAPK inflammatory pathway.

Objective:To compare the real-world efficacy and safety profile of tenofovir amibufenamid (TMF) and tenofovir alafenamide (TAF) tablets in the treatment of patients with chronic hepatitis B (CHB).Methods:This retrospective study included patients with chronic hepatitis B who received TMF and TAF antiviral treatment at the Infectious Disease Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January 2021 to December 2023. The primary and secondary outcome was to study the patient HBV DNA conversion rate (<20 IU/ml), alanine aminotransferase (ALT) normalization rate, renal function, and lipid levels of patients at 48 weeks of treatment. The comparison of data between measurement data groups was differentiated using a t-test and Mann-Whitney U test. The inter-group comparison rate in count data was performed using the χ2 test or Fisher's exact probability. Results:A total of 440 cases were enrolled, including 220 in the TMF group (63 treatment-na?ve and 157 treatment-experienced) and 220 cases in the TAF group (61 treatment-na?ve and 159 treatment-experienced). In terms of efficacy, the HBV DNA seroconversion rates in the TMF group and TAF group were 90.5% and 85.2% ( P=0.372), respectively, while the ALT normalization rates were 92.1% and 88.5% ( P=0.505), respectively, at 48 weeks of treatment. The HBV DNA-negative conversion rate for the newly treated patients was 99.4% and 98.7%, respectively ( P=1.000), while the rates of ALT normalization were 94.9% and 92.3%, respectively ( P=0.863). In terms of safety profile, the serum creatinine level was lower in the TMF group than that in the TAF group at 48 weeks of treatment [TMF group 66.5 (56.3, 78.3) μmol/L, TAF group 70.6 (60.7, 77.8) μmol/L, Z=-2.282, P=0.022]. However, there was no statistically significant difference in other renal function and tubular function related indicators between the two groups of patients ( P>0.05). The serum high-density lipoprotein levels were higher in the TMF group than those in the TAF group [TMF 1.4 (1.1, 1.6) mmol/L vs. TAF group 1.3 (1.1, 1.6) mmol/L, Z=-2.204, P=0.027] at 48 weeks of treatment. However, there was no statistically significant difference in other blood lipid indicators between the two groups of patients ( P>0.05). Conclusion:There is no statistically significant difference in efficacy and safety profiles between TMF and TAF at 48 weeks in the treatment of patients with chronic hepatitis B, and the overall safety profile is favorable.

Objective: To investigate the diagnosis, treatment and prognosis of nonodontogenic periapical lesions and to provide a reference for clinical diagnosis and treatment. Methods: A case of a patient with right upper molar pulp with apical penetration and local occlusion admitted to the West China Stomatological Hospital of Sichuan University was retrospectively analyzed, and the curative effect of microapical surgery and pith preservation was also analyzed. Results : The imaging features of tooth 16 showed periradicular radiolucency combined with local radiopaque lesions around the distal buccal apical area. Endodontic microsurgery was performed under local anesthesia. Soft tissue coverage was observed in the distal buccal apical area during the surgery, and no radiopaque tissue was detected. The distal buccal root apex was cut by 3 mm, and mineral trioxide aggregate was used for root-end backfilling. The postoperative pathological results revealed fibrous connective tissue. One-week recall X-ray examination showed tight root-end backfilling and no periradicular radiolucency; an electrical test of pulp vitality showed positive results. The four-year follow-up showed that there was no discoloration in tooth 16 and no significant difference in thermal and electrical tests of pulp vitality compared with control teeth. Combining the clinical manifestations, imaging features, surgical exploration results and pathological reports, the case was most likely to be cemental hypoplasia. Through the literature review, the treatment and healthy pulp preservation of such cases by endodontic microsurgery under the premise of preserving teeth has not been reported. Conclusion For maxillary posterior teeth with periapical lesions but healthy pulp, accurate estimation of pulp status, endodontic microsurgical exploration and application of bioactive materials can achieve vital pulp preservation while removing the lesions.

Objective By a sequencing panel consisting of 50 targeted genes, aiming at depicting the molecular landscape of ET, PV, and PMF, which are three major subtypes of MPN, to provide valuable information in the diagnosis and prognosis of MPN.Methods A retrospective study was conducted of 53 patients from Huashan hospital and Changhai hospital. All patients were diagnosed in accordance with the 2016 WHO diagnostic criteria for MPN, including 31 cases of ET(11 males, 20 females, median age 55 years), 17 cases of PV(12 males, 5 females, median age 65 years), and 5 cases of PMF(4 males, 1 females, median age 67 years), and underwent next-generation of DNA sequencing of their bone marrow or blood samples. The genetic analyses were performed on bone marrow or peripheral blood. Referring to COSMIC, dbSNP, Clinvar and other public databases, we analyzed the sequencing data, and elucidated the mutation profile of MPN patients, combining with their clinic information. Results In addition to the typical JAK2, CALR, and MPL mutations, pathogenic mutations in other 11 genes were detected, as well as 4 SNPs that confer individual susceptibility to MPNs (rs4858647, rs9376092, rs58270997, rs621940). The average rate of mutated genes was 2.3 genes per patient. In all patients (53 cases), the mutated genes detected were TET2, EZH2, ASXL1, MIR662, SF3B1, BARD1, DNMT3A, KIT, RUNX1, TP53, NRAS according to their mutational frequency. Conclusions Applying next-generation sequencing technology, multi-gene sequencing of a bunch of typical BCR-ABL-negative MPN patients can be performed at one time within 2 working days, and pathogenic mutations other than JAK2, CALR, MPL can be found, which has a bright prospection in clinic.

Objective To observe the clinical effect of CT-guided percutaneous puncture of stylomastoid foramen and radiofrequency ablation on primary hemifacial spasm. Methods Twenty-seven patients with primary hemifacial spasm, admitted to and accepted CT-guided percutaneous puncture of stylomastoid foramen and radiofrequency ablation in our hospital from August 2018 to May 2019, were chosen in our study. Clinical data and efficacy of the patients were retrospectively analyzed. Results All patients were punctured to the stylomastoid foramen precisely under the guidance of CT localization; 21 could detect facial muscle twitch with 0.1-0.5 mA current, and positive results were also found in 6 patients with 0.5 mA current after adjusting the position of the needle tip. After standard radio frequency ablation (mean 83.3 ℃ for 23.7 seconds), 26 patients had complete disappearance of facial spasm, but left grade II (n=18) or grade III (n=8) facial paralysis; one patient with disappearance of abnormal electromyographic response waveform as the end criterion only partially relieved, but no facial paralysis. No facial hematoma, intracranial hemorrhage, infection, or death occurred. Follow-up for 2-12 months showed no recurrence or aggravation of facial paralysis. Conclusion CT-guided percutaneous puncture of stylomastoid foramen by radio frequency ablation can effectively treat primary hemifacial spasm, but there will be mild facial paralysis.

OBJECTIVETo explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism.

METHODSAfter being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg), POFS model(70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups(70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase III((KATIII() by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy(TEM).

RESULTSAs compared to control group, exercise score decreased(P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT III( decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1, and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats, while such damage was improved in antagonist group.

CONCLUSIONThe increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.

Animals ; Fatigue ; Hippocampus ; Humans ; Injections, Intraperitoneal ; Male ; Postoperative Period ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Signal Transduction ; Transaminases

Objective To explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism. Methods After being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg ), POFS model (70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups (70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg ). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase Ⅲ (KATⅢ) by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy (TEM). Results As compared to control group, exercise score decreased (P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT Ⅲ decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1 , and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats , while such damage was improved in antagonist group. Conclusion The increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.

Objective To explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism. Methods After being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg ), POFS model (70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups (70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg ). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase Ⅲ (KATⅢ) by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy (TEM). Results As compared to control group, exercise score decreased (P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT Ⅲ decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1 , and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats , while such damage was improved in antagonist group. Conclusion The increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.

Aim To observe the effects of the L-dopa methyl ester (LDME) on the pattern visual evoked potentials (P-VEP) and the expression of c-fos mRNA in neurons of the visual cortex of kittens with strabismic amblyopia, and explore the therapeutic effect of L-dopa methyl ester on amblyopia and its action mechanism.Methods 30 normal kittens were randomly divided into 6 groups: low dose of L-dopa methyl ester (20 mg·kg~(-1)), medium dose of L-dopa methyl ester (40 mg·kg~(-1)), and high dose of L-dopa methyl ester (80 mg·kg~(-1)),positive control (L-dopa 40 mg·kg~(-1)),normal control, and model control group.The surgery for producing iatrogenic convergent strabismus was performed on 4 weeks old kittens(normal control group excluded). After the confirmation of the development of amblyopia by pattern visual evoked potential,L-dopa methyl ester,L-dopa and normal saline were given to the corresponding animals, respectively. The P-VEP of amblyopia eyes was observed after one month, and the technique of in situ hybridization was used to detect the expression of c-fos mRNA.Results L-dopa methyl ester could reduce obviously the length of P100 peak latency of the cat strabismic amblyopes, and increase the amplitude of P100. The positive staining cells of strabismic cat visual cortex were less than those of normal cats, whose difference was significant (P<0.01).Positive staining cells in the treatment group were significantly increased when compared with that of the model group (P<0.01).Conclusion L-dopa methyl ester can significantly improve the conduction and sensory function in the model of strabismic amblyopia cats. The mechanism may be related to the increased amount of L-dopa methyl ester into the cerebral cortex and regulation of the expression of c-fos mRNA.

OBJECTIVE: To study the inhibitory effects of traditional chinese medicine Compound Liuyuexue (CLYX) on hepatitis B surface antigen(DHBsAg) and hepatitis B e-antigen(DHBeAg).METHODS: One-day old guangxi brown spotted ducks infected with DHBV were used as the hepatitis B virus infected animal model. Positive ducks were detected by PCR at 13 days after the infection of DHBV, and were randomly divided into five groups: the high dose group, middle dose group and low dose group of Compound Liuyuexue(CLYX), model group, and positive control group, with 10 ducks in each group. CLYX was given ig.for 14 days. Serum sampling was scheduled at 0, 7, 14 days respectively and 3 days after drug withdrawal, and the contents of DHBsAg and DHBeAg in serum were measured by ELISA. RESULTS: The serum DHBsAg and DHBeAg contents in high dose and middle dose groups of CLYX were decreased significantly(P