Abstract Ring finger protein 183(RNF183) is an E3 ubiquitin ligase that catalyzes the covalent attachment of ubiquitin molecules to substrate proteins. RNF183 is expressed in tissues such as kidney and testis, and it is mainly localized to the endoplasmic reticulum, Golgi apparatus, and lysosomes in cells. As one of the components of the endoplasmic reticulum membrane, it participates in the endoplasmic reticulum stress-responsive pathway that affects cellular and protein ubiquitination. In recent years, the study of E3 ubiquitin ligase member-RNF183 with various diseases such as colorectal cancer, endometrial cancer and bladder cancer has gradually increased. In this review, the role of RNF183 in colorectal cancer, inflammatory bowel disease and other diseases, as well as biological functions such as endoplasmic reticulum stress are summarized, aiming to provide reference ideas for the study of related diseases.

The angiogenic microenvironment is a new blood vessel with different molecular and functional characteristics that sprouts on the original blood vessels through different mechanisms,which directly affects the process of tumor cell growth,proliferation,and migration and has an important impact on the occurrence and development of precancerous lesions of gastric cancer.Correa mode has shown that precancerous lesions of gastric cancer is the key pathological stage before the occurrence of gastric cancer,and it is of great significance to advance the prevention and treatment strategy to this stage.TCM believes that qi deficiency and blood stasis is the key pathogenesis of precancerous lesions of gastric cancer,and its basic treatment is to replenish qi and remove blood stasis,and based on the syndrome differentiation,drugs with the efficacy of nourishing yin and tonifying stomach,soothing the liver and regulating qi,resolving phlegm and dispersing lumps,and clearing heat and dampness for treatment.This article discussed the correlation between precancerous lesions of gastric cancer and angiogenic microenvironment and its regulatory pathways,and summarized the methods and mechanisms of TCM in the treatment of precancerous lesions of gastric cancer from the perspective of regulating angiogenic microenvironment-related pathways,in order to provide a reference for the treatment of precancerous lesions of gastric cancer with TCM.

Objective:To evaluate the diagnostic efficacy of FibroScan combined with various noninvasive diagnostic models for liver fibrosis in patients with chronic hepatitis B (CHB) complicated with nonalcoholic fatty liver disease (NAFLD), and to establish a new predictive model with common clinical indicators.Methods:From January 2016 to May 2024, the clinical data of 118 CHB patients complicated with NAFLD from the First Affiliated Hospital of Zhengzhou University, who underwent liver biopsy and FibroScan examination were respectively analyzed. According to the Scheuer scoring system, different diagnostic endpoints were set based on the degree of liver fibrosis (S0 to S1, ≥S2, ≥S3, and S4), fibrosis stage ≥S2 was designated as the criterion for significant liver fibrosis. Fibrosis-4 (FIB-4), γ-glutamyl transpeptidase (GGT) to platelet ratio (GPR), GGT-age-platelet-international normalized ratio (GAPI) model, S index, King index and Forns index were calculated according to the common clinical indicators. The independent t test or Mann-Whitney U test was used to compare the two groups. Spearman rank correlation was used to analyze the correlation between each noninvasive diagnostic method and the degree of liver fibrosis. Receiver operating characteristic curve (ROC) was plotted, and the DeLong test was performed to compare the area under the curve (AUC), and to evaluate the predictive value of FibroScan combined with various noninvasive diagnostic models for the diagnosis of liver fibrosis. The laboratory indicators were compared between patients with non-significant liver fibrosis and patients with significant liver fibrosis. And the indicators with statistically significant differences ( P<0.05) in the univariate analysis were further analyzed by multivariate logistic regression to establish a new predictive model for liver fibrosis. Hosmer-Lemeshow test was used to assess the model′s goodness of fit. Results:The results of Spearman rank correlation showed that FIB-4, GPR, FibroScan, GAPI model, S index, King index, and Forns index were positively correlated with the stage of liver fibrosis ( r=0.413, 0.458, 0.512, 0.473, 0.533, 0.380 and 0.478, all P<0.001). The results of ROC analysis indicated that among combination of FibroScan and other diagnostic models, the AUC values of FibroScan+ FIB-4, FibroScan+ Forns index were relatively high in ≥S2 and ≥S3, which were 0.804 and 0.907, respectively. The platelet count ((200.65±50.89)×10 9/L vs. (169.96±63.68)×10 9/L), total cholesterol ((4.69±0.77) mmol/L vs. (4.32±1.00) mmol/L), high-density lipoprotein (HDL) (1.28 (1.05, 1.46) mmol/L vs. 1.08 (0.92, 1.21) mmol/L), total protein (74.00 (70.63, 77.08) g/L vs. 68.80 (64.60, 73.55) g/L), albumin (47.06 (44.65, 48.81) g/L vs. 44.70 (41.55, 46.20) g/L), and globulin (26.80 (24.48, 29.70) g/L vs. 25.80 (23.05, 27.60) g/L) of the non-significant liver fibrosis group were higher than those of the significant liver fibrosis group, and the differences were statistically significant ( t=2.74, 2.09; Z=-3.30, -3.88, -3.95, -2.01; P=0.007, =0.040, =0.001, <0.001, <0.001, =0.044). GGT (27.50 (17.00, 41.75) U/L vs. 37.00 (22.50, 87.00) U/L), the liver stiffness measurement (LSM) in the non-significant hepatic fibrosis group was lower than the significant liver fibrosis group (6.85 (5.60, 9.26) kPa vs. 11.60 (7.08, 17.26) kPa), and the differences were statistically significant ( Z=-2.73, -4.39; P=0.006, <0.001). The result of multivariate logistic regression analysis revealed that globulin, albumin, HDL, and LSM were independent factors of liver fibrosis ( OR (95% confidence interval)=0.865 (0.759 to 0.985), 0.804 (0.691 to 0.935), 0.128 (0.023 to 0.711), and 1.251 (1.091 to 1.433), respectively; P=0.029, 0.025, 0.019, 0.001). A novel model, GLAH, was established with globulin, LSM, albumin, and HDL. The AUC for diagnosing liver fibrosis degree ≥S2, ≥S3, and S4 was 0.847, 0.938, and 0.909, respectively, which were higher than those of the above models. The positive predictive value for diagnosing liver fibrosis degree ≥S2 with GLAH>1.12 as the cutoff value was 95.8%. The negative predictive value for excluding fibrosis stage ≥S2 with GLAH<-1.41 was 92.3%. This approach could reduce the number of liver biopsies by 48.3% (57/118), with an accuracy of 94.7% (54/57). Conclusions:The clinical value of FibroScan combined with FIB-4 or Forns index is better in the diagnisis of fibrosis stage ≥S2 and ≥S3. The GLAH model has higher diagnostic value and can accurately predict the degree of liver fibrosis in CHB patients complicated with NAFLD, thus reducing the need for liver biopsy.

Objective:To evaluate the diagnostic efficacy of FibroScan combined with various noninvasive diagnostic models for liver fibrosis in patients with chronic hepatitis B (CHB) complicated with nonalcoholic fatty liver disease (NAFLD), and to establish a new predictive model with common clinical indicators.Methods:From January 2016 to May 2024, the clinical data of 118 CHB patients complicated with NAFLD from the First Affiliated Hospital of Zhengzhou University, who underwent liver biopsy and FibroScan examination were respectively analyzed. According to the Scheuer scoring system, different diagnostic endpoints were set based on the degree of liver fibrosis (S0 to S1, ≥S2, ≥S3, and S4), fibrosis stage ≥S2 was designated as the criterion for significant liver fibrosis. Fibrosis-4 (FIB-4), γ-glutamyl transpeptidase (GGT) to platelet ratio (GPR), GGT-age-platelet-international normalized ratio (GAPI) model, S index, King index and Forns index were calculated according to the common clinical indicators. The independent t test or Mann-Whitney U test was used to compare the two groups. Spearman rank correlation was used to analyze the correlation between each noninvasive diagnostic method and the degree of liver fibrosis. Receiver operating characteristic curve (ROC) was plotted, and the DeLong test was performed to compare the area under the curve (AUC), and to evaluate the predictive value of FibroScan combined with various noninvasive diagnostic models for the diagnosis of liver fibrosis. The laboratory indicators were compared between patients with non-significant liver fibrosis and patients with significant liver fibrosis. And the indicators with statistically significant differences ( P<0.05) in the univariate analysis were further analyzed by multivariate logistic regression to establish a new predictive model for liver fibrosis. Hosmer-Lemeshow test was used to assess the model′s goodness of fit. Results:The results of Spearman rank correlation showed that FIB-4, GPR, FibroScan, GAPI model, S index, King index, and Forns index were positively correlated with the stage of liver fibrosis ( r=0.413, 0.458, 0.512, 0.473, 0.533, 0.380 and 0.478, all P<0.001). The results of ROC analysis indicated that among combination of FibroScan and other diagnostic models, the AUC values of FibroScan+ FIB-4, FibroScan+ Forns index were relatively high in ≥S2 and ≥S3, which were 0.804 and 0.907, respectively. The platelet count ((200.65±50.89)×10 9/L vs. (169.96±63.68)×10 9/L), total cholesterol ((4.69±0.77) mmol/L vs. (4.32±1.00) mmol/L), high-density lipoprotein (HDL) (1.28 (1.05, 1.46) mmol/L vs. 1.08 (0.92, 1.21) mmol/L), total protein (74.00 (70.63, 77.08) g/L vs. 68.80 (64.60, 73.55) g/L), albumin (47.06 (44.65, 48.81) g/L vs. 44.70 (41.55, 46.20) g/L), and globulin (26.80 (24.48, 29.70) g/L vs. 25.80 (23.05, 27.60) g/L) of the non-significant liver fibrosis group were higher than those of the significant liver fibrosis group, and the differences were statistically significant ( t=2.74, 2.09; Z=-3.30, -3.88, -3.95, -2.01; P=0.007, =0.040, =0.001, <0.001, <0.001, =0.044). GGT (27.50 (17.00, 41.75) U/L vs. 37.00 (22.50, 87.00) U/L), the liver stiffness measurement (LSM) in the non-significant hepatic fibrosis group was lower than the significant liver fibrosis group (6.85 (5.60, 9.26) kPa vs. 11.60 (7.08, 17.26) kPa), and the differences were statistically significant ( Z=-2.73, -4.39; P=0.006, <0.001). The result of multivariate logistic regression analysis revealed that globulin, albumin, HDL, and LSM were independent factors of liver fibrosis ( OR (95% confidence interval)=0.865 (0.759 to 0.985), 0.804 (0.691 to 0.935), 0.128 (0.023 to 0.711), and 1.251 (1.091 to 1.433), respectively; P=0.029, 0.025, 0.019, 0.001). A novel model, GLAH, was established with globulin, LSM, albumin, and HDL. The AUC for diagnosing liver fibrosis degree ≥S2, ≥S3, and S4 was 0.847, 0.938, and 0.909, respectively, which were higher than those of the above models. The positive predictive value for diagnosing liver fibrosis degree ≥S2 with GLAH>1.12 as the cutoff value was 95.8%. The negative predictive value for excluding fibrosis stage ≥S2 with GLAH<-1.41 was 92.3%. This approach could reduce the number of liver biopsies by 48.3% (57/118), with an accuracy of 94.7% (54/57). Conclusions:The clinical value of FibroScan combined with FIB-4 or Forns index is better in the diagnisis of fibrosis stage ≥S2 and ≥S3. The GLAH model has higher diagnostic value and can accurately predict the degree of liver fibrosis in CHB patients complicated with NAFLD, thus reducing the need for liver biopsy.

OBJECTIVE: To explore the genetic basis for child with congenital cataract. METHODS: The child was subjected to next-generation sequencing. Candidate variant was verified by Sanger sequencing of his family members. RESULTS: The proband was found to harbor novel heterozygous variants of c.855del and c.872dup of the GJA8 gene, which were inherited from his father and mother, respectively. Neither of these two variants has been reported. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the c.855del and c.872dup variants were classified as likely pathogenic (PVS1_S+PM2+PP4) and pathogenic (PVS1_S+PM2+PM3+PP4), respectively. CONCLUSION The c.855del and c.872dup variants of the GJA8 gene probably underlay the congenital cataract in this patient.
Child ; Humans ; Cataract/congenital* ; Family ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Mutation ; Pedigree

Objective:To evaluate the efficacy and safety of modified FC/ATG pretreatment in the treatment of severe aplastic anemia(SAA).Methods:From June 2012 to June 2020, clinical data of 64 patients with severe aplastic anemia undergoing allogeneic hematopoietic stem cell transplantation with modified FC/ATG(Flu 30 mg·m -2·d -l, -5~-2 d、CTX 50 mg·kg -1·d -1~-2 d、ATG: 2.5 mg·kg -1·d -1, -5~-2 d) pretreatment were retrospectively analyzed.There were MSD-HSCT ( n=29) and Haplo-HSCT ( n=35). Results:One patient died of intracerebral hemorrhage before transplantation and the remainders were completely implanted.During a median follow-up period of 14.5(1-95) months, overall survival (OS) rate of 92.2%.It was significantly higher than OS rate of 67.2% in the treatment of SAA by foreign pretreatment regimens containing low-dose TBI.And pretreatment scheme containing FC+ BU/TBI had an OS of slightly >91.3% in the treatment of SAA.The 3-year OS rates were 85.7% and 93.5% in Haplo-HSCT and MSD-HSCT groups ( P=0.058). The OS rate of SAA Haplo-HSCT/MSD-HSCT group was similar to that of " Beijing Protocol" (BU/CY+ ATG) (89%, 91%). The viral infection rates of EB and CMV were significantly higher in haplo-HSCT group than those in MSD-HSCT group and inter-group difference was statistically significant ( P<0.05). However, univariate analysis showed that two groups had no effect on survival time ( P=0.403, P=0.132). Univariate analysis showed that survival time was significantly associated with the presence of Ⅲ-Ⅳ° aGVHD and the presence of severe complications ( P=0.007, P=0.001). Further multivariate analysis revealed that severe complication was an independent risk factor for survival ( P=0.003). Conclusions:The efficacy of improved FC/ATG pretreatment in the treatment of SAA in MSD-HSCT or Haplo-HSCT is higher than other domestic and international pretreatment schemes in OS rate, safety and effectiveness.Onset of severe complication and association with Ⅲ ~ Ⅳ ° aGVHD are the influencing factors for patient survival.The efficacy of Haplo-HSCT group is similar to that of MSD-HSCT group.It may be employed as an alternative donor for SAA patients without fully congruent donors.

OBJECTIVE: To investigate the effect of ABT-263,an anti-apoptotic protein inhibitor,on human cutaneous squamous cell carcinoma A431 cells,and to explore its molecular mechanisms. METHODS: i) Total protein was extracted from human immortalized epidermal cells( Ha Ca T cells) and A431 cells in logarithmic growth phase. The protein expression of B-cell lymphoma-2( BCL-2) and BCL2-like 1( BCL-XL) was detected by Western blotting. ii) The A431 cells were treated with ABT-263( inhibitor group) and dimethyl sulfoxide( control group) at a concentration of 50 μmol/L for 4 and 9 hours. The morphological changes of the cells were examined by transmission electron microscopy. iii) The A431 cells were treated with 0,10,25,40,and 50 μmol/L of ABT-263 for 24 hours,and the cell viability was determined by CCK-8 assay. iv) The A431 cells were treated with different doses of ABT-263,and the expression of cleaved Caspase-3, cleaved poly( ADP-ribose) polymerase-1( PARP-1), phosphorylated protein kinase B [p AKT(ser473)],phosphorylated glycogen synthase kinase-3β(p GSK3β) and phosphorylated histone H2 AX(γH2 AX) was detected by Western blot. RESULTS: The relative expression of BCL-2 and BCL-XL in A431 cells were higher than those in Ha Ca T cells( P < 0. 01). Transmission electron microscopy results showed that A431 cells in inhibitor group gradually changed from normal morphology to apoptotic morphology,showing loss of microvilli,increased nuclear chromatin density and aggregation around the nuclear membrane,and nuclear fragmentation. The cell viability of A431 cells in 10,25,40 and 50 μmol/L groups were lower than those in control group( P < 0. 05). The relative expression of cleaved Caspase-3 and cleaved PARP-1 in A431 cells in 10,30 and 50 μmol/L groups were higher than those in control group( P < 0. 05).The relative expression of p AKT( ser473) and p GSK3β in A431 cells in 10,25,40 and 50 μmol/L groups were lower than those of the control group( P < 0. 05) and γH2 AX protein expression was higher than that of the control group( P <0. 05). A431 cell viability and p GSK3β protein expression decreased with the increase of inhibitor dosage( P < 0. 01).The relative expression of cleaved Caspase-3 and γH2 AX protein increased with the increase of inhibitor dosage( P <0. 01),showing dose-effect relationship. CONCLUSION: ABT-263 can induce apoptosis of A431 cells through mitochondria pathway and induce the inactivation of AKT/GSK3β pathway,which can promote the apoptosis of A431 cells with a doseeffect relationship.

The objective of this study was to determine the concentrations of calcium,phosphorus and magnesium in blood and compare the differences in seven areas of Heilongjiang province,and then estimate calcuim-phosphorus metabolism of beef cattle in seven beef cattle farms to provi detheoretical foundation for the prevention of calcium phosphorus metabolism diseases of beef cattle.Seven beef cattle farms of Daqing,Shuangyashan,Jiusan and Mudanjiang in Heilongjiang province were selected as the survey sites,which were recorded as group A (both grazing and stall-feeding in Shuangyashan),group B (stall-feeding mode in Shuangyashan),group C (stall-feeding mode in Daqing),group D (grazing mode in Jiusan),group E (both grazing and stall-feeding in Daqing),group F (both grazing and stall-feeding in Daqing) and group G (stall-feeding mode in Mudanjiang).Then the concentrations of Ca,Mg,P,free fatty acid (NEFA),glucose (Glc) and β-hydroxybutyric acid (BHBA) in the blood were compared to estimate the calcuim-phosphorus metabolic states.Results showed that the concentrations of calcium,magnesium and phosphorus in the plasma of 65 beef cattle in seven survey sites were within the normal range,and there was no significant difference in calcium concentration among seven sites.The P contents in group C and G were significantly higher those that in group A and B(P＜0.01),which in group C was significantly higher than those in group D,E and F (P＜0.01),which in group G was significantly higher than those in group D,E and F(P＜0.01).NEFA content in group B was significantly higher than that in group D (P＜0.05),and there was no difference among other groups.The concentration of Glc in group A was significantly higher than that in group E (P＜0.05),which in group B was significantly higher than those in group A and D,and was very significantly higher than those in group E,F and G (P＜0.01),which in group C was very significantly higher than those in group A,D,E,F and G (P＜0.01),which in group C was significantly higher than those in group A,D,E,F and G (P＜0.01),which in group D was significantly higher than that in group E (P＜0.05),and which in group F was significantly higher than that in group E (P＜0.05).The concentration of BHBA in group C,D and E were significantly higher than that in group A (P＜0.01),which in group C was significantly higher than that in group B (P＜0.05),which in group D and E was significantly higher than that in group B (P＜0.01),which in group C was significantly higher than that in group G (P＜0.01),which in group D was significantly higher than those in group F and G (P＜0.01),and in group E was highly significantly higher than that in group F and G (P＜0.01).Overall,there were not calcuim-phosphorus metabolic disorders within the seven beef cattle farms which were selected,but it is also necessary to strengthen feeding management and health care to prevent the occurrence of nutrition and metabolic diseases.

Objective:To compare the therapeutic effects between the Governor Vessel-regulating, liver-soothing and mind-calming needling and the routine acupuncture therapy for insomnia due to liver fire disturbing the heart.
Methods:A total of50 cases with insomnia were randomly divided by the random numberl table into the two groups, 25 cases in each group. The observation group was treated with the Governor Vessel-regulating, liver-soothing and mind-calming needling, while the control group was treated with the routine acupuncture therapy. The two groups were treated for five sessions per week, ten sessions as a course. After 3-course treatment, the therapeutic effects and the improvement of Pittsburgh sleep quality index (PSQI) were observed.
Results:After treatment for three courses, the total effective rate was 100% in the treatment group and 92% in the control group. The difference in the therapeutic effect between the two groups was statistically significant (P<0.05). After the treatment, thesleep latency, sleep duration, habitual sleep efficiency, subjective sleep quality, sleeping disturbances, daytime dysfunction, and total PSQI scores in the patients of the two groups were obviously improved in comparing those before treatment, with significant differences (allP<0.01). After treatment, the inter-group differences in the sleep latency, sleep duration, habitual sleep efficiency, subjective sleep quality, and total PSQI scores were statistically significant (all P<0.01); the differences in the scores of sleeping disturbances and daytime dysfunction is not statistical significant (all P>0.05).
Conclusion:Thetherapeutic effect of Governor Vessel-regulating, liver-soothing and mind-calming needling is better for insomnia due to liver fire disturbing the heart than the routine acupuncture therapy.

Objective: To compare the different therapeutic effects of acupuncture and Phenolphthalein for constipation due to intestinal qi stagnation. Methods:A total of 50 patients with constipation due to intestinal qi stagnation were randomly divided into an acupuncture group and a medication group by the random digital table, 25 cases in each group. The patients in the acupuncture group were treated by puncturing Gongsun (SP 4), Sanyinjiao (SP 6), Taichong (LR 3), Zusanli (ST 36), Shangjuxu (ST 37), Hegu (LI 4), Lieque (LU 7), and Tianshu (ST 25), once every day, and 7 d as one course, for continuous 3 courses; while the patients in the medication group were given Phenolphthalein, 7 d as one course, for continuous 3 courses. Compared the Cleveland clinic constipation score (CCS) between the two groups after one course, 3 courses and 3 months after the treatment, as well as the frequency of defecation within one week. Results:After one week of treatment, CCS scores and frequency of defecation per week were significantly changed in both groups compared with those before treatment (P<0.05), and CCS scores and frequency of defecation per week were improved more significantly in the patients of the medication group than in those of the acupuncture group (P<0.01). After 3 weeks of treatment, CCS scores and frequency of defecation per week were significantly changed in both groups compared with those before treatment (P<0.05), and CCS scores and frequency of defecation per week were improved more significant in the patients of the acupuncture group than in those of the medication group (P<0.05). Three months after the end of treatment, CCS scores and frequency of defecation per week were significantly changed in both groups compared with those before treatment (P<0.05), and CCS scores and frequency of defecation per week were improved more significantly in the patients of the acupuncture group than in those of the medication group (P<0.05). Conclusion:Acupuncture and medication are effective in the treatment of constipation due to intestinal qi stagnation. Their short-term therapeutic effect is similar, but the long-term therapeutic effect is better in the acupuncture group than in the medication group.