Objective To report the clinical and peripheral neuropathological findings in two patients with autosomal recessive Charcot-Marie-Tooth disease 2K(AR-CMT2K).Methods Case one was a nine year-old girl.She had distal weakness of lower limbs for six years, with calf atrophy and contracture of Achilles tendon for three years.Case two was an eight year-old boy.He had distal weakness of lower limbs with contracture of Achilles tendon and calf muscle atrophy for three years, and proximal weakness of low limbs for two years.The motor nerve conduction velocities in median nerves were 48.1 m/s in case one and 47.6 m/s in case two.The compound motor action potential amplitude of median nerves decreased by 46% in case one and 69% in case two.Sural nerve biopsies and gene targeted next-generation sequencing were performed in both patients.Results Density of myelinated fibers was 8 407/mm2 in case one and 7 714/mm2 in case two.The ratio of myelinated fibers with diameter over 8 μm was 2.6% in case one and 0 in case two.Both patients had small regenerating cluster of myelinated fibers.Thin myelinated fibers appeared in case one.In case two, atypical onion bulb formations with focal folded myelin appeared, and electromicroscopy revealed mitochondrial aggregate in axons.Compound heterozygous mutations of ganglioside-induced differentiation associated protein 1 gene were detected in both patients, including c.767A>G(p.H256R) and c.466G>A (p.A156T) in case one and c.767A>G and 845G>A(p.R282H) in case two.Conclusions Contracture of Achilles tendon may appear in early childhood of AR-CMT2K patients.The main pathological changes in sural nerve are loss of large myelinated fibers, mitochondrial aggregate in axons and myelin abnormalities.

Objective To analyze clinical features and sum up experience for the treatment of ischemic bowel disease. Methods Clinical data of 73 patients with the diagnosis of ischemic bowel disease were retrospectively analyzed. ResultsTwenty-eight patients were male and 45 patients were female. The median of age was 65 years (range of 38 to 89 years). Forty-eight patients were associated with hypertension, 23%(17/73) patients had a history of coronary disease and 15% (11/73) had diabetes. Seventy patients presented symptom of abdominal pain and 93% (68/73) had hematochezia. Symptoms relieved by conservative treatment in 96% (63/66) patients. Nine patients underwent a surgery. One patient died of sepsis postoperatively. One suffered from colostomy necrosis and leakage of the rectum segment. Conclusion 1. Elder patients presenting symptoms of abdominal pain and hematochezia, especially with a history of cardio-cerebrovascular disease and diabetes should be considered for the possibility of ischemic bowel disease. 2. Most patients with ischemic bowel disease could be successfully treated by conservative therapy. 3. Surgery for patients with chronic relapsing and nonresponsible symptoms was difficult and patients often suffer from high postoperative complications.

Objective:To compare the clinical effect of 0.02% atropine eye drops once every two days and 0.01% atropine eye drops once every day in myopia control and adverse reactions in children.Methods:A randomized controlled study was performed.The 231 Han nationality myopic children wearing full-corrected single-vision spectacle lenses enrolled from June 2016 to June 2017 in The First Affiliated Hospital of Zhengzhou University and Henan Eye Hospital were divided into two groups by random number table, with 110 children in the 0.02% atropine group and 121 children in the 0.01% atropine group.The subjects were treated with 0.02% atropine eye drops once every two days or 0.01% atropine eye drops once every day to each eye before bedtime for one year.Ninety-two cases and 101 cases were followed up for one year in the 0.02% and 0.01% atropine group, respectively.The right eyes were selected as experimental eyes, and the spherical equivalent refraction (SER), axial length (AL), amplitude of accommodation (AMP), pupil diameter (PD), anterior chamber depth (ACD), and corneal curvature were recorded at baseline and 12 months after treatment.Discomfort symptoms were also observed during the 1-year follow-up.The study protocol was approved by an Ethics Committee of The First Affiliated Hospital of Zhengzhou University (No.2016-35). Written informed consent was obtained from guardians prior to any treatment.Results:After 1 year of treatment, the mean SER change was (-0.46±0.49)D and (-0.48±0.46)D, and the mean AL change was (0.38±0.21)mm and (0.39±0.19)mm, and the mean AMP change was (-1.49±0.29)D and (-1.61±0.26)D, and the mean PD change was (0.72±0.44)mm and (0.70±0.40)mm in the 0.02% atropine group and 0.01% atropine group, respectively.There was no significant difference in the change of SER, AL, AMP, PD between the two groups (all at P>0.05). There were 21 cases (19.1%) in the 0.02% atropine group and 25 cases (20.7%) in the 0.01% atropine group that represented mild photophobia in bright sunlight, which disappeared in 12 and 13 cases during 1-6 months respectively.The photophobia symptoms of the remaining children were alleviated.There existed 5 cases (4.5%) and 6 cases (5.0%) in the two groups that developed mild near blurred vision that lasted no more than 1 month. Conclusions:Compared with 0.01% atropine eye drops once a day, 0.02% atropine once every two days has the same efficacy on controlling myopia progression in children with no more adverse reactions.

Objective To explore the influencing factors on short -term efficacy of intravenous thrombolysis with rt -PA.Methods The clinical data of the 95 acute ischemic stroke(AIS)patients who received thrombolytic therapy were analyze.Multivariate logistic regression analysis was used to determine the possible influencing factors. Results Fifty -six(58.95%)patients had favourable outcomes after thrombolytic therapy for 24 hours.Multivariate logistic regression analysis indicated that diabetes(OR =3.933,95% CI 1.199 ~12.897)and TOAST classification (OR =1.448,95% CI 1.032 ~2.032 )were the independent predictors of short -term outcome.Conclusion Diabetes and TOAST classification are the major influencing factors of short -term efficacy after intravenous thrombolysis with rt -PA.It should pay attention screening patients for intravenous thrombolysis therapy and predicting the efficacy of thrombolysis.

The rapid advancements in artificial intelligence(AI)and computational sciences,particularly through the introduction of artificial intelligence drug design(AIDD)and computer-aided drug design(CADD)technologies,have revolutionized pathways in drug development.These include techniques such as natural language processing,image recognition,deep learning,and machine learning.By employing advanced algorithms and data processing techniques,these technologies have significantly enhanced the efficiency and success rate of R&D processes.In drug discovery,AI technologies have accelerated the identification of drug targets,screening of candidate drugs,pharmacological assessments,and quality control,effectively reducing R&D risks and costs.This article delves into the application of AIDD and CADD in drug development,analyzing their roles in enhancing the success rates and efficiencies of drug design,exploring their future trends,and addressing the potential challenges.

Objective To study the effect of autophagy regulation on hypoxia/reoxygenation injury(H/RI)in mouse spermatogonia,and to explore the effect of autophagy on ischemia-reperfusion injury(IRI)in mouse testicular tissue.Methods The mouse spermatogonial cell line GC1 spg was used as the research object to construct the H/RI model.Rapamycin(RAPA)and 3-methyladenine(3-MA)were used as autophagy ago-nists and inhibitors.The control group,the model group,the autophagy agonist intervention group(H/RI+autophagy agonist intervention),and the autophagy inhibitor intervention group(H/RI+autophagy inhibitor intervention)were set up.The cells proliferation ability of each group was detected by methyl thiazol tetrazoli-um(MTT)method.The release level of reactive oxygen species(ROS)and apoptosis level of each group were detected by flow cytometry.The expression levels of autophagy-related gene Beclin1 and apoptosis-relat-ed genes Bcl-2 and Bax mRNA in each group were detected by real-time fluorescence quantitative PCR(qPCR).The expression levels of autophagy-related proteins LC3-Ⅰ,LC3-Ⅱ,Beclin1,p62 and apoptosis-relat-ed proteins Bcl-2,Bax,caspase-3 in each group were detected by Western blot.Results Compared with the control group,the proliferation abiliy,the expression levels of Beclin1 and Bcl-2 mRNA in the model group were significantly decreased(P＜0.01),the relative expression levels of p62 and Bcl-2 proteins were significantly decreased(P＜0.01).The ROS level,apoptosis rate and the mRNA expression level of Bax were significantly increased(P＜0.01),and the protein expresion levels of Beclin1,Bax,caspase-3 and the protein ratio of LC3-Ⅱ/LC3-Ⅰ were significantly increased(P＜0.01).Compared with the model group,the cell proliferation a-bility,the expression levels of Beclin1 and Bcl-2 mRNA in the autophagy agonist intervention group were the protein ratio of significantly increased(P＜0.01),the protein expression levels of Beclin1 and Bcl-2 and the protein ration of LC3-Ⅱ/LC3-Ⅰ were significantly increased(P＜0.01).The ROS level,apoptosis rate and the expression level of Bax mRNA were significantly decreased(P＜0.01),and the protein expression levels of p62,Bax,caspase-3 and the protein ratio of LC3-Ⅱ/LC3-Ⅰ were significantly decreased(P＜0.01).Com-pared with the model group,the cell proliferation ability,the mRNA expression levels of Beclin1 and Bcl-2 in the autophagy inhibitor intervention group were significantly decreased(P＜0.01),the protein expression lev-els of Beclin1 and Bcl-2 protein were significantly decreased(P＜0.01).The ROS level,apoptosis rate and the mRNA expression level of Bax were significantly increased(P＜0.01),and the protein expression levels of p62,Bax,caspase-3 and the protein ratio of LC3-Ⅱ/LC3-Ⅰwere significantly iecreased(P＜0.01).Conclusion Enhanced au-tophagy can inhibit apoptosis of spermatogonia and repair H/RI in mice,which provides a theoretical basis for the treatment of testicular tissue IRI.

OBJECTIVE Angiogenesis therapy has attracted interest as a potential treatment for hepatocellular carcinoma (HCC). In this study, we investigated the anti-proliferative activities and anti-angiogenesis effects of saikosaponins (SS)-b on hepatocellular carcinoma (HCC) and its regulation on VEGF/ERK/HIF-1α signal pathway. METHODS H22 hepatoma-bearing mice model and HepG-2 cells were used to study the anti-tumor and anti-angiogenesis effects of SS-b in vivo and in vitro. Pathological change of tumor tissue was observed by HE staining, the microvascular changes were detected by immunohistochemical method. The effects of SS-b on angiogenesis were examined by using the chick embryo chorioallantoic membrane (CAM) model. The effects of SS- b on proliferation, migration and invasion were investigated by MTT assay, scratch wound healing assay and transwell assay inhuman umbilical vein endothelial cell (HUVEC) and HepG2 cells in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase-2/9(MMP-2/9), hypoxia-inducible factor-1α (HIF-1α) expression and the phosphorylation of extracellular regulated kinase(ERK) were analyzed using RT-PCR and Western-blot. RESULTS SS-b effectively inhibited the tumor growth of H22 mice in vivo. The inhibitory rate of tumor was 49.1%, 50.7%, 66.1% in SS-b 5, 10 and 20 mg·kg-1 group respectively. HE staining results showed that SS-b induced tumor necrosis and nuclear dissolution in H22 mice. Moreover, SS-b also reduced the number of microvessels of tumor tissue in H22 mice significantly and suppressed the angiogenesis of CAM induced by b-FGF. SS-b had an obvious inhibitory effect on cell proliferation, migration and invasion of HUVEC cells and HepG-2 cells. These effects were associated with down-regulation of the expression of MMP2/9 and suppression of VEGF/ERK/HIF-1α signaling in H22 mice and Hep-G2 cells. CONCLUSION Our findings showed that SS-b exerts anti-tumor effects by inhibit?ing tumor angiogenesis via regulating VEGF/ERK/HIF-1α signal pathway in vivo and in vitro.

Objective To evaluate the effects of 0.0％ and 0.02％ atropine on pupil diameter (PD) and accommodation amplitude (AMP) in myopic children and analyze its relation factors.Methods A prospective randomized controlled trial design was adopted.One hundred and ninety-three myopia children were included from June to October,2016 in the First Affiliated Hospital of Zhengzhou University,all the children completed one-year follow-up.All the children were divided into three groups randomly,with 72,74 and 80 myopic children in 0.01％ atropine group,0.02％ atropine group and control group,respectively.The myopic children in 0.01％ atropine group and 0.02％ atropine group wore single-vision spectacle lenses and were treated with 0.01％ and 0.02％ atropine eye drops nightly,respectively.The myopic children in the control group wore spectacle lenses only.The PD and AMP were measured at baseline,and 4,8 and 12 months after treatment.Results There were no significant difference of baselinePD and AMP among the three groups (F=9.321,P=0.820;F=13.209,P=0.220).Compared with basline,after 12 months,the PD increased by 0.75,0.84 and 0.02 mm in 0.01％ atropine group,0.02％ atropine group and control group,respectively.There were statistically significant differences of PD among three groups at different time points (Fgroup =2.168,P=0.013;Ftime =2.139,P=0.015;Finteraction =2.148,P=0.001).Compared with baseline,the PD of 0.01％ atropine group and 0.02％ atropine group were increased 4,8 and 12 months after treatment,and the difference was statistically significant (all at P＜0.001).The PD was stable in control group.After 12 months,the AMP were reduced by 1.25,1.12 and 0.28 D in 0.01％ atropine group,0.02％ atropine group and control group,respectively.There were statistically significant differences of AMP among the three groups at the different time points (Fgroup =18.346,P =0.034;Ftime =1.823,P =0.002;Fintercation =3.239,P =0.023).Compared with baseline,the AMP of 0.01％ atropine group and 0.02％ atropine group were increased 4,8 and 12 months after treatment,and the differences were statistically significant (all at P＜0.05).The AMP remained stable in control group.The change of PD in 0.01％ atropine group and 0.02％ atropine group was correlated with age,baseline PD and baseline eye axis length,respectively (β =0.060,P =0.019;β =-0.440,P＜0.001;β =-0.37,P =0.045).The change in AMP of the atropine group was significantly correlated with the baseline adjustment range (β =-0.71,P＜0.001).Conclusions 0.01％ and 0.02％ atropine show similar effects on pupil diameter and accommodation amplitude after 12 months of treatment in myopic children.

OBJECTIVETo identify non-invasive biomarkers for diagnosis and/or prognosis of liver fibrosis in chronic hepatitis B (CHB).

METHODSPeripheral blood samples were obtained from 48 patients with CHB, including 24 with mild fibrosis (stage 1, S1) and 24 with severe fibrosis (stage 4, S4), and subjected to Ficoll density gradient centrifugation in order to obtain enriched samples of peripheral blood mononuclear cells (PBMCs).The PBMC proteomes of the two groups were assessed by first separating the total proteins by two-dimensional gel electrophoresis (2DE) and then identifying the differentially expressed proteins by liquid chromatography combined with tandem mass spectrometry (LCMS/MS).

RESULTSThe enriched PBMC samples from the S1 group and the S4 group had similar amounts of platelets [(19.268+/- 6.413) * 109/L and(19.480+/- 6.538) * 109/L, respectively); however, for both, the platelet amounts were 5 to 15-fold lower than that of the normal reference (100-300 *109/L). There was no significant difference found between the platelet amounts in the S1 patients and healthy controls (P=0.930). Twelve differentially expressed proteins were identified through 2DE-LC-MS/MS, including proteins such as moesin and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 that are involved in various biological processes like cell movement, cell adhesion, kinase signaling and transcription.

CONCLUSIONs The 12 proteins with differential expression in S1 and S4 patients with CHB and liver fibrosis may represent markers related to development and/or progression of liver fibrosis.

Biomarkers ; Disease Progression ; Electrophoresis, Gel, Two-Dimensional ; Hepatitis B, Chronic ; complications ; Humans ; Leukocytes, Mononuclear ; chemistry ; metabolism ; Liver Cirrhosis ; etiology ; metabolism ; pathology ; Mass Spectrometry ; Prognosis ; Proteome ; Proteomics ; Tandem Mass Spectrometry

Objective To investigate the safety and efficacy of CT-guided 125I seed implantation in the treatment of metastatic lymph nodes within the abdomen.Methods Data of 55 patients who underwent CT-guided 125I seed implantation with a total of 63 metastatic lymph nodes within the abdomen were retrospectively analyzed.The efficacy was evaluated.Results 125I seeds were successfully implanted in all 55 patients,and the radiation dose reached the pre-operation plan requirements.The response rate of 1,3,6,9 and 12 months after operation was 76.19％ (48/63),80.65％ (50/62),71.43％(30/42),77.50％(31/40) and 78.95％(30/38),respectively.And the clinical benefit rate was 93.65％(59/63),88.71％(55/62),80.95 ％ (34/42),85.00％(34/40) and 84.21％(32/38),respectively.There were 42 patients combined with abdominal pain and back pain before the operation.Among them,39 patients (39/42,92.86％) relieved 1 month after operation.No severe complication occurred intraoperatively or postoperatively,such as inhibition of bone marrow,bleeding or infection.The survival rate of 1,3,6,9 and 12 months postoperatively was 100％,98.20％,61.80％,58.20％ and 54.50％,respectively.Conclusion CT-guided 125I seed implantation is one of the safe and effective methods for treating metastatic lymph nodes within the abdomen.