The innate immune response is the first line of defense for the host against viral infections. Targeted degradation of pathogenic microorganisms through autophagy, in conjunction with pattern recognition receptors synergistically inducing the production of interferon (IFN), constitutes an important pathway for the body to resist viral infections. Rubicon, a Run domain Beclin 1-interacting and cysteine-rich domain protein, has an inhibitory effect on autophagy and IFN production. On the one hand, Rubicon, as a component of the phosphoinositide 3-kinase (PI3K) complex, interacts with different domains of vacuolar protein sorting 34 (Vps34), ultraviolet radiation resistance associated gene (UVRAG), guanosine triphosphate (GTP) kinase, and RAS oncogene family member 7 (Rab7) to mediate the inhibition of autophagy maturation; on the other hand, Rubicon inhibits the ubiquitination of nuclear factor κB essential modulator (NEMO) and the dimerization of interferon regulatory factor 3 (IRF3), thereby blocking the signal transduction related to IFN production. Research has revealed that various viruses, such as Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), Sendai virus (SeV), and hepatitis C virus (HCV), achieve innate immune evasion by regulating the expression or function of Rubicon. Rubicon is expected to be a new target for antiviral therapy.
Humans ; Autophagy/immunology* ; Immunity, Innate ; Interferons/immunology* ; Immune Evasion ; Animals ; Virus Diseases/virology* ; Signal Transduction ; Viruses/immunology* ; Intracellular Signaling Peptides and Proteins/immunology* ; Autophagy-Related Proteins

Objective To investigate the relationships of the expression of microRNA-487a-3p (miR-487a-3p) and A kinase-interacting protein 1 (AKIP1) mRNA in the endometrial cancer (EC) tissue with the patient survival within 5 years after surgery. Methods The EC tissue and adjacent normal tissue samples were collected from 130 EC patients who underwent surgical treatment at the Fourth Hospital of Shijiazhuang from September 2016 to April 2019.qRT-PCR was employed to determine the expression levels of miR-487a-3p and AKIP1 mRNA.The patients were followed up for 5 years after surgery to record the survival status.After removal of the patients who missed follow-up,78 surviving patients were recorded as the EC survival group,and 34 deceased patients were recorded as the EC death group.The dual luciferase reporter gene assay was conducted to verify the targeting relationship between miR-487a-3p and AKIP1 mRNA.Comparison was conducted for the expression levels of miR-487a-3p and AKIP1 mRNA between adjacent normal tissue and EC tissue,the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue among patients with different clinical pathological parameters,and the clinical pathological parameters and the expression levels of miR-487a-3p and AKIP1 mRNA in the EC tissue between the EC survival group and the EC death group.The correlations of miR-487a-3p and AKIP1 mRNA levels in the EC tissue with the degree of tumor differentiation,International Federation of Gynecology and Obstetrics (FIGO) stage,lymph node metastasis,and depth of muscle invasion were analyzed.The relationships of miR-487a-3p and AKIP1 mRNA with patient prognosis and the risk factors affecting the survival of EC patients within 5 years after surgery were analyzed to evaluate the value of miR-487a-3p and AKIP1 mRNA levels in predicting the survival of EC patients within 5 years after survival. Results The EC tissue showed lower miR-487a-3p level (0.41±0.08 vs. 1.00±0.05;t=71.306,P<0.001) and higher AKIP1 mRNA level (2.35±0.37 vs. 1.00±0.03;t=41.465,P<0.001) than the adjacent normal tissue.The miR-487a-3p low expression group and AKIP1 mRNA high expression group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer than the miR-487a-3p high expression group and AKIP1 mRNA low expression group,respectively (all P<0.05).The results of dual luciferase reporter gene assay showed that the relative activity of luciferase in the miR-487a-3p small interfering RNA (siRNA)+AKIP1 mRNA-wild type (WT) group was higher than that in the miR-487a-3p empty vector+AKIP1 mRNA-WT group (2.85±0.19 vs. 1.00±0.04;t=23.339,P<0.001).There was no significant difference in the relative activity of luciferase between the miR-487a-3p empty vector+AKIP1 mRNA-mutant type (MUT) group and the miR-487a-3p siRNA+AKIP1 mRNA-MUT group (1.04±0.05 vs. 1.05±0.03;t=0.420,P=0.683).MiR-487a-3p in the EC tissue had negative correlations with AKIP1 mRNA,FIGO stage,lymph node metastasis,and depth of muscle invasion and a positive correlation with the degree of tumor differentiation (all P<0.001).AKIP1 mRNA had positive correlations with FIGO stage,lymph node metastasis,and depth of muscle invasion and a negative correlation with the degree of tumor differentiation (all P<0.001).The 5-year overall survival rates in the miR-487a-3p high expression group and AKIP1 mRNA low expression group (89.47% and 84.91%) were higher than those in the miR-487a-3p low expression group and AKIP1 mRNA high expression group (49.09% and 55.93%),respectively (both P<0.05).The EC death group had higher proportions of patients with low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,and deep invasion of muscle layer,higher AKIP1 mRNA level in the EC tissue,and lower miR-487a-3p level than the EC survival group (all P<0.05).Low tumor differentiation,FIGO stage Ⅲ to Ⅳ,lymph node metastasis,deep invasion of muscle layer,low miR-487a-3p level,and high AKIP1 mRNA level were independent risk factors for the survival of EC patients within 5 years after surgery (all P<0.05).The area under curve (AUC) values of miR-487a-3p and AKIP1 mRNA alone (0.785 and 0.789,respectively) were lower than that of their combination (0.908) in predicting the survival of EC patients within 5 years after surgery (both P<0.05). Conclusion The EC tissue has a low miR-487a-3p level and a high AKIP1 mRNA level,both of which are correlated with clinicopathological parameters and prognosis and can be used to predict the survival of EC patients within 5 years after surgery.
Humans ; Female ; Endometrial Neoplasms/pathology* ; MicroRNAs/genetics* ; RNA, Messenger/genetics* ; Adaptor Proteins, Signal Transducing/genetics* ; Middle Aged ; Survival Rate ; Nuclear Proteins

Objective:To analyze the significance of total vitamin D(tVD),total procollagen type Ⅰ amino-terminal propeptide(tPINP)and β-CrossLaps(β-CTx)in the staging and prognosis of patients with multiple myeloma(MM).Methods:A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group(MM group),and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group.The expression levels of tVD,tPINP and β-CTx in the two groups were detected by chemiluminescence method.The differences in the expression levels of tVD,tPINP and β-CTx among MM patients at different ISS stages were analyzed.The expression levels of tVD,tPINP and β-CTx in MM patients with different levels of hemoglobin(Hb),serum calcium(Ca),creatinine(Crea),albumin(ALB),β2-microglobulin(β2-MG)and lactate dehydrogenase(LDH)were compared.The correlations between the expression levels of tVD,tPINP,β-CTx and the aforementioned clinical parameters were analyzed,respectively.The relationship between the expression levels of tVD,tPINP,β-CTx and the progression-free survival(PFS)of MM patients was analyzed.Results:The expression level of tVD in the MM group was significantly lower than that in the control group(21.73±14.45 ng/ml vs 30.78±9.94 ng/ml,P=0.022).The expression level of β-CTx in the MM group was significantly higher than that in the control group(1.43±0.99 ng/ml vs 0.53±0.29 ng/ml,P=0.013).The tVD level in MM patients with ISS stage Ⅰ-Ⅱ was significantly higher than that of MM patients with ISS stage Ⅲ(29.50±14.59 ng/ml vs 12.62±7.73 ng/ml,P=0.028),indicating that the higher the ISS stage,the lower the tVD level.The tPINP andβ-CTx levels in MM patients with high Ca levels(＞2.65 mmol/L)were significantly higher than those in patients with low Ca levels(≤ 2.65 mmol/L)(P=0.016,P=0.021).The tVD level of MM patients was positively correlated with the ALB level(r=0.570),tPINP was positively correlated with Ca and β2-MG levels(r=0.791,r=0.673),and β-CTx was positively correlated with tPINP level(r=0.616).The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group(P=0.041).Conclusion:The expression level of tVD is decreased in MM patients,which can be used as an indicator to evaluate the disease stage and prognosis of the patients.The β-CTx expression level is increased in MM patients.tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.

This study was aimed at analyzing the molecular epidemiological characteristics of Brucella in Shanxi Province from 2020 to 2023.A total of 479 clinical Brucella strains were identified in Shanxi Province from 2020 to 2023.The strains were preliminarily identified through biochemical methods.The genome was extracted for MLVA-16 typing and whole genome sequencing.MLVA-16 clustering results indicated 50.5％to 100％strain similarity.The strains were typed into 204 VNTR types by MLVA-16,whereas the panel 2B locus showed polymorphism.The clustering results indicated 11 VNTR types with more than five strains.Whole genome sequencing was performed for VNTRS types in large clusters.cgMLST clustering indica-ted similar clustering of strains.Brucella was effectively distinguished through MLVA typing.The phylogenetic relationship and epidemiological characteristics of strains can be distinguished more effectively by cgMLST.Specific Brucella genotypes were transmitted in Shanxi Province from 2020 to 2023.

OBJECTIVE: To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN). METHODS: A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014. RESULTS: A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer. CONCLUSIONS No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.
Humans ; Retrospective Studies ; Incidence ; Carcinoma, Hepatocellular ; Liver Neoplasms/epidemiology* ; Kidney Diseases/chemically induced* ; Aristolochic Acids/adverse effects*

Objective:To investigate the clinical effects of modified automatic hemorrhoidal ligation using elastic string (RPH-4) combined with Xiaozhilling injection for grade Ⅲ hemorrhoids.Methods:The prospective randomized controlled study was conducted. The clinical data of patients with grade Ⅲ hemorrhoids who underwent modified RPH-4 combined with Xiaozhiling injection in Traditional Chinese Medicine Hospital of Chongqing Shapingba District from July 2021 to December 2022 were selected. Patients with grade Ⅲ hemorrhoids who meeting the inclusion criteria were randomly divided into the experimental group and the control group using a random number table method. Patients in the experiment group underwent submucosal injection of the Xiaozhilling injec-tion followed by modified RPH-4, and patients in the control group underwent submucosal injection of the 0.9% sodium chloride solution followed by modified RPH-4. Observation indicators: (1) grouping of enrolled patients; (2) postoperative situations; (3) short-term efficacy; (4) long-term efficacy. Com-parison of measurement data with normal distribution between groups was conducted using the inde-pendent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the nonparameter test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping of enrolled patients. A total of 120 patients were selected. There were 72 males and 48 females, aged 48(range, 18-69)years, including 60 cases in the experiment group and 60 cases in the control group, respectively. There was no significant difference in gender, age, type of hemorrhoids, time to hemorrhoid prolapsis, stool blood, symptom score and Wexner score between the two groups ( P>0.05), confounding bias ensured comparability. At the end of the study, there were 59 cases in the experimental group and 58 cases in the control group. (2) Postoperative situations. There were 5 cases of secondary bleeding after modified RPH-4 in the experiment group and 15 cases of secondary bleeding after modified RPH-4 in the control group, showing a significant difference between the two groups ( χ2=6.239, P<0.05). The post-operative hemorrhoidal shedding time was (6.9±1.4)days in the experiment group, versus (8.1±2.2)days in the control group, showing a significant difference between the two groups ( t=-3.566, P<0.05). (3) Short-term efficacy. There were 59 cases in the experiment group and 58 cases in the control group completing short-term follow-up. The cure rate was 88.14%(52/59) in the experiment group, versus 84.48%(49/58) in the control group, showing no significant difference in short-term efficacy between the two groups ( χ2=0.331, P>0.05). The wound healing time was (24±5)days in the experi-ment group, versus (25±5)days in the control group, showing no significant difference between the two groups ( t=-1.082, P>0.05). (4) Long-term efficacy. There were 59 cases in the experiment group and 58 cases in the control group completing long-term follow-up. None of patient in the two groups had anal incontinence. Cases of hemorrhoid recurrence (blood stool or prolapse) and cases of rectal hard segment in the experiment group were 2 and 1, respectively, and there was no anorectal stenosis. Cases of hemorrhoid recurrence (blood stool or prolapse) and cases of anorectal stenosis were 8 and 1, respectively, and there was no rectal hard segment. There was no significant difference of above situations between the two groups ( P>0.05). Conclusion:The modified RPH-4 combined with Xiaozhiling injection for grade Ⅲ hemorrhoids can achieve double solid and hemorrhoidal removal efficacy, which can further reduce the risk of complications after severe hemorrhoids modified RPH-4 alone treatment.

This study was aimed at analyzing the molecular epidemiological characteristics of Brucella in Shanxi Province from 2020 to 2023.A total of 479 clinical Brucella strains were identified in Shanxi Province from 2020 to 2023.The strains were preliminarily identified through biochemical methods.The genome was extracted for MLVA-16 typing and whole genome sequencing.MLVA-16 clustering results indicated 50.5％to 100％strain similarity.The strains were typed into 204 VNTR types by MLVA-16,whereas the panel 2B locus showed polymorphism.The clustering results indicated 11 VNTR types with more than five strains.Whole genome sequencing was performed for VNTRS types in large clusters.cgMLST clustering indica-ted similar clustering of strains.Brucella was effectively distinguished through MLVA typing.The phylogenetic relationship and epidemiological characteristics of strains can be distinguished more effectively by cgMLST.Specific Brucella genotypes were transmitted in Shanxi Province from 2020 to 2023.

Objective:To investigate the clinical effects of modified automatic hemorrhoidal ligation using elastic string (RPH-4) combined with Xiaozhilling injection for grade Ⅲ hemorrhoids.Methods:The prospective randomized controlled study was conducted. The clinical data of patients with grade Ⅲ hemorrhoids who underwent modified RPH-4 combined with Xiaozhiling injection in Traditional Chinese Medicine Hospital of Chongqing Shapingba District from July 2021 to December 2022 were selected. Patients with grade Ⅲ hemorrhoids who meeting the inclusion criteria were randomly divided into the experimental group and the control group using a random number table method. Patients in the experiment group underwent submucosal injection of the Xiaozhilling injec-tion followed by modified RPH-4, and patients in the control group underwent submucosal injection of the 0.9% sodium chloride solution followed by modified RPH-4. Observation indicators: (1) grouping of enrolled patients; (2) postoperative situations; (3) short-term efficacy; (4) long-term efficacy. Com-parison of measurement data with normal distribution between groups was conducted using the inde-pendent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the nonparameter test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping of enrolled patients. A total of 120 patients were selected. There were 72 males and 48 females, aged 48(range, 18-69)years, including 60 cases in the experiment group and 60 cases in the control group, respectively. There was no significant difference in gender, age, type of hemorrhoids, time to hemorrhoid prolapsis, stool blood, symptom score and Wexner score between the two groups ( P>0.05), confounding bias ensured comparability. At the end of the study, there were 59 cases in the experimental group and 58 cases in the control group. (2) Postoperative situations. There were 5 cases of secondary bleeding after modified RPH-4 in the experiment group and 15 cases of secondary bleeding after modified RPH-4 in the control group, showing a significant difference between the two groups ( χ2=6.239, P<0.05). The post-operative hemorrhoidal shedding time was (6.9±1.4)days in the experiment group, versus (8.1±2.2)days in the control group, showing a significant difference between the two groups ( t=-3.566, P<0.05). (3) Short-term efficacy. There were 59 cases in the experiment group and 58 cases in the control group completing short-term follow-up. The cure rate was 88.14%(52/59) in the experiment group, versus 84.48%(49/58) in the control group, showing no significant difference in short-term efficacy between the two groups ( χ2=0.331, P>0.05). The wound healing time was (24±5)days in the experi-ment group, versus (25±5)days in the control group, showing no significant difference between the two groups ( t=-1.082, P>0.05). (4) Long-term efficacy. There were 59 cases in the experiment group and 58 cases in the control group completing long-term follow-up. None of patient in the two groups had anal incontinence. Cases of hemorrhoid recurrence (blood stool or prolapse) and cases of rectal hard segment in the experiment group were 2 and 1, respectively, and there was no anorectal stenosis. Cases of hemorrhoid recurrence (blood stool or prolapse) and cases of anorectal stenosis were 8 and 1, respectively, and there was no rectal hard segment. There was no significant difference of above situations between the two groups ( P>0.05). Conclusion:The modified RPH-4 combined with Xiaozhiling injection for grade Ⅲ hemorrhoids can achieve double solid and hemorrhoidal removal efficacy, which can further reduce the risk of complications after severe hemorrhoids modified RPH-4 alone treatment.

Objective To identify the sets of lymphocytes that could systematically evaluate immune function of colorectal cancer patients, based on the expression of colorectal cancer T cells, natural killer (NK) cells, and NKT cell surface protein receptors. Methods Peripheral blood samples from 144 patients with colorectal cancer and 87 healthy controls were collected, and the differences in surface receptors of lymphocyte subsets in peripheral blood of patients and healthy controls were analyzed by means of flow cytometry and cell culture. Results Compared with healthy control group, the percentage of peripheral blood total lymphocytes, CD16^brightCD56^dimNK cells and NKT cells decreased in patients with colorectal cancer. The percentage of T cells, CD16^brightCD56^dimNK cells and NKT cell surface inhibitory receptors T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains (TIGIT) increased; T cells, NK cells, NKT cell surface chemokine receptor C-C motif chemokine receptor 7 (CCR7) slightly decreased. Conclusion There are differences in the proportion of NK cell subsets and the expression profile of surface receptors in peripheral blood of patients with colorectal cancer.
Humans ; Lymphocyte Subsets ; Killer Cells, Natural ; Lymphocyte Count ; Receptors, Chemokine ; Colorectal Neoplasms

OBJECTIVE: To observe the variability of hemoglobin (HB) level in patients with renal anemia, and to analyze its relationship with effect of repeated blood transfusion therapeutic in patients. METHODS: A retrospective cohort study and propensity score matching method were used, 60 patients with renal anemia who had effective treatment with repeated blood transfusion in Changzhou No.2 People's Hospital from May 2018 to May 2021 were retrospectively analyzed and set as the effective group; 153 patients with renal anemia who had ineffective treatment with repeated blood transfusion in the hospital in the same period were collected and set as the ineffective group, the propensity score matching method was used, the patients who were effective and ineffective in repeated blood transfusion were matched 1∶1 for analysis; the medical records and laboratory indexes of the two groups were checked; the Hb level of patients within 6 months (1/month) were recorded, the residual standard deviation (Res-SD) of Hb of patients was calculated according to the Hb level and evaluated the variability of Hb level; the relationship between HB variability level and therapeutic effect of repeated blood transfusion in patients with renal anemia was analyzed. RESULTS: After propensity score matching, there was no statistical significant difference between the two groups in terms of baseline data such as age, sex, dialysis age and BMI (P>0.05). The levels of serum albumin and transferrin of patients in the ineffective group were significantly lower than those of patients in the effective group (P<0.05); at 1 and 2 months of the observation period, there was no statistical significant difference in Hb levels of patients in both groups (P>0.05); the Hb level of patients in the ineffective group was significantly lower than that of patients in the effective group at 3, 5 and 6 months, and significantly higher than that of patients in the effective group at 4 months (P<0.05); the Res-SD of male patients and female patients in the ineffective group were respectively significantly higher than that of male patients and female patients in the effective group (P<0.05). Logistic regression analysis results showed that high variability of Hb level (Res-SD) was a risk factor for the ineffective treatment of repeated blood transfusion in patients with renal anemia (OR>1, P<0.05); the decision curve results showed that, when the high-risk threshold was 0.0-1.0, Res-SD predicted the net benefit rates of male and female patients with renal anemia were greater than 0, which was clinically significant, the smaller the high-risk threshold in the above range, the greater the net benefit rate. CONCLUSION The therapeutic effect of repeated blood transfusion in patients with renal anemia may be related to the variability of Hb level.
Humans ; Male ; Female ; Retrospective Studies ; Hemoglobins/therapeutic use* ; Anemia/therapy* ; Chronic Disease ; Blood Transfusion ; Kidney Diseases