MicroRNA-133b inhibits hepatocellular carcinoma cell progression by targeting Sirt1.

MicroRNAs (miRNAs) are a class of small non-coding RNAs that function as critical gene regulators by targeting mRNAs for translational repression or degradation. In this study, we showed that the expression level of miR-133b was decreased, while Sirt1 mRNA expression levels were increased in hepatocellular carcinoma (HCC) and cell lines, and we identified Sirt1 as a novel direct target of miR-133b. The over-expression of miR-133b suppressed Sirt1 expression. In addition, miR-133b over-expression resulted in attenuating HCC cell proliferation and invasion together with apoptosis increase in vitro. HepG2 cell transplantation revealed that up-regulation of miR-133b could inhibit HCC tumor genesis in vivo. Forced expression of Sirt1 partly rescued the effect of miR-133b in vitro. Furthermore, our study showed that miR-133b over-expression or Sirt1 down-regulation elevated E-cadherin expression, and repressed glypican-3 (GPC3) and the anti-apoptotic proteins (Bcl-2, Bcl-xL, and Mcl-1) expression. The inhibition of GPC3 expression repressed Bcl-2, Bcl-xL, and Mcl-1 expression, and elevated E-cadherin expression. Moreover, the Sirt1 up-regulation resulted in increases in HCC cell proliferation and invasion together with decreases apoptosis, and increases in the cytosolic accumulation and nuclear translocation of the transcription factor ß-catenin in vitro. But the effect of Sirt1 up-regulation was partly reversed by GPC3 down-regulation in vitro. Taken together, these findings provide insight into the role and mechanism of miR-133b in regulating HCC cell proliferation, invasion and apoptosis via the miR-133b/Sirt1/GPC3/Wnt ß-catenin axis, and miR-133b may serve as a potential therapeutic target in HCC in the future.

Astragaloside IV protects against polymicrobial sepsis through inhibiting inflammatory response and apoptosis of lymphocytes.

BACKGROUND: Sepsis is a major clinical challenge in modern medicine, representing one of the leading causes of death in developed countries. The syndrome is a consequence of a dysregulated immune response, including early uncontrolled systemic inflammation and prolonged immunosuppression in the late phase. The present study was conducted to investigate the therapeutic effects of astragaloside IV (ASI-IV) on the cecal ligation and puncture (CLP)-induced sepsis in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into sham control + vehicle, CLP + vehicle, and CLP + ASI-IV groups. ASI-IV (3 mg/kg) was intravenously injected 1 h after CLP surgery. Survival rate, bacterial clearance, inflammatory mediators, phagocytes emigration, histopathology, and lymphocyte apoptosis were examined. The effects of ASI-IV on peritoneal macrophage activation and its underlying mechanisms were also evaluated. RESULTS: We reported that treatment with ASI-IV significantly improved survival in septic mice. In agreement with this protective effect, the pathologic damage that was typically seen in lung and spleen was ameliorated; the level of bacterial burden was lessened; inflammatory cytokines and chemokines in circulation were profoundly reduced; lymphocyte apoptosis was inhibited. ASI-IV suppressed LPS-induced macrophage activation through inhibiting NF-κB and ERK1/2 signaling pathways. CONCLUSIONS: ASI-IV protected mice against polymicrobial sepsis by inhibiting inflammatory response and lymphocyte apoptosis. Therefore, ASI-IV might provide a novel therapeutic approach for septic patients.

Association of leukocyte mitochondrial DNA content with glioma risk: evidence from a Chinese case-control study.

BACKGROUND: Increasing evidence suggests that alterations in mitochondrial DNA (mtDNA) content may be implicated in the tumorigenesis of several malignancies. However, the association between mtDNA content in peripheral blood lymphocytes (PBLs) and glioma risk has not been investigated. METHODS: Real-time PCR was used to examine the mtDNA content in PBLs of 414 glioma patients and 414 matched controls in a hospital-based case-control study. The association between mtDNA content and glioma risk was evaluated using an unconditional multivariate logistic regression model. RESULTS: We found that glioma patients exhibited a significantly higher median mtDNA content than healthy controls (0.99 vs. 0.71, P < 0.001). Unconditional multivariate logistic regression analysis adjusting for age, gender, smoking status, and family cancer history showed that there was an S-shaped association between mtDNA content and glioma risk. Higher mtDNA content was significantly associated with an elevated risk of glioma. Compared with the first quartile, the odds ratio (95% confidence interval) for subjects in the second, third, and fourth quartiles of mtDNA content were 0.90 (0.52-1.53), 3.38 (2.15-5.31), and 5.81 (3.74-9.03), respectively (P for nonlinearity = 0.009). Stratified analysis showed that the association between mtDNA content and glioma risk was not modulated by major host characteristics. CONCLUSIONS: Our findings demonstrate for the first time that a higher mtDNA content in PBLs is associated with an elevated risk of glioma, which warrants further investigation in larger populations.

Epidemiological survey of elderly patients diagnosed with COVID-19 at mobile field hospitals.

BACKGROUND: During the COVID-19 pandemic, the mobile field hospital, a rapidly deployable healthcare facility for emergency care, was effective in ensuring rapid diagnosis and treatment of patients with mild or asymptomatic SARS-CoV2 infections, effectively preventing the spread of COVID-19. OBJECTIVE: We conducted a survey to gain a thorough understanding of the epidemiological traits among the elderly who contracted the Omicron variant of the SARS-CoV-2 virus at a mobile field hospital set up at the National Exhibition and Convention Center (Shanghai). METHODS: A cross-sectional study approach was employed to examine various factors such as demographic characteristics, clinical features, vaccination status, and nucleic acid testing. We utilized the DezhenTech Integrated Electronic Medical Record Platform (Municipal Isolation Hospital) to collect data and focused on elderly individuals infected with COVID-19 in the fifth isolation zone of the mobile field hospital set up at the National Exhibition and Convention Center (Shanghai). The patients were categorized into different age groups for analysis. RESULTS: Among the 3,183 elderly patients, 54.7% were males and 45.3% were females, with an average age of 65.32 ± 4.41 years. Among them, 47.8% (1523/3183) were 60-64 years old, 34.0% (1082/3183) were 65-69 years old, 14.0% (444/3183) were 70-74 years old, 3.2% (103/3183) were 75-79 years old, and 1.0% (31/3183) were ⩾ 80 years old. The majority (95.7%) of the elderly patients with chronic conditions had hypertension, diabetes, and coronary heart disease. The first viral nucleic acid screening showed a higher positive rate in the community and hospital fever clinics. The cumulative positive rate of the nucleic acid test in the mobile field hospital was 38.7%. The average CT value of the COVID-19 ORF1ab gene was 34.56 ± 5.98, while the average CT value of the N gene was 33.10 ± 6.50. The patients took an average of 3.40 ± 0.45 days to test negative, with a positive rate of 15.4% and an average hospital stay of 7.45 ± 0.53 days. The overall rate of COVID-19 vaccine coverage was 68.0%, with an enhanced coverage rate of 40% and a non-coverage rate of 29.3%. CONCLUSIONS: The overall prognosis for elderly patients who experienced a mild or asymptomatic SARS-CoV-2 Omicron infection at the mobile field hospital was favorable, although the vaccination rate in general was not high. By effectively managing underlying health conditions, the duration of their hospital stay in the mobile field hospital was reduced.

FOXM1/DVL2/Snail axis drives metastasis and chemoresistance of colorectal cancer.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Metastasis and chemoresistance are regarded as the two leading causes of treatment failure and high mortality in CRC. Forkhead Box M1 (FOXM1) has been involved in malignant behaviors of cancer. However, the role and mechanism of FOXM1 in simultaneously regulating metastasis and chemoresistance of CRC remain poorly understood. Here, we found that FOXM1 was overexpressed in oxaliplatin- and vincristine-resistant CRC cells (HCT-8/L-OHP and HCT-8/VCR) with enhanced metastatic potential, compared with HCT-8 cells. FOXM1 overexpression increased migration, invasion and drug-resistance to oxaliplatin and vincristine in HCT-8 cells, while FOXM1 knockdown using shFOXM1 impaired metastasis and drug-resistance in HCT-8/L-OHP and HCT-8/VCR cells. Moreover, FOXM1 up-regulated Snail to trigger epithelial-mesenchymal transition-like molecular changes and multidrug-resistance protein P-gp expression, while silencing Snail inhibited FOXM1-induced metastasis and drug-resistance. We further identified that disheveled-2 (DVL2) was crucial for FOXM1-induced Snail expression, metastasis and chemoresistance. Furthermore, FOXM1 bound to DVL2, and enhanced nuclear translocation of DVL2 and DVL2-mediated transcriptional activity of Wnt/ß-catenin known to induce Snail expression. In conclusion, FOXM1/DVL2/Snail axis triggered aggressiveness of CRC. Blocking FOXM1/DVL2/Snail pathway simultaneously inhibited metastasis and chemoresistance in CRC cells, providing a new strategy for successful CRC treatment.

[Effects of high thoracic epidural anesthesia on ventricular remodeling and expression of beta(3)-adrenoceptor in rats with heart failure induced by acute myocardial infarction].

OBJECTIVE: To investigate the effect of high thoracic epidural anesthesia on ventricular remodeling and cardiac function in rats with heart failure induced by myocardial infarction, and to investigate their mechanism. METHODS: Rats that had been established successively model were randomly divided into S group (n = 12), HTEA group and CHF group (24/group). 9.0 g/L normal sodium 100 microl/kg was injected to epidural cavity twice a day separately in group S and group CHF. 1.25 g/L bupivacaine 100 microl/kg was injected to epidural cavity twice a day in group HTEA. Epidural injection was started 24 hrs after the epidural surgery and continued 4 weeks. Then the change of cardiac function was observed by using echocardiogram. The ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW) were measured. Noninfarct ventricular tissue were stained with hematoxylin-eosin (HE) and Masson's trichrome respectively. beta(3)-adrenoceptor levels and eNOS levels were detected with reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: LVEDD and LVESD were significantly decreased in the group HTEA compared with group CHF (P < 0.01), while LVEF% and LVFS% were significantly increased (P < 0.01). The ratios HW/BW and LVW/BW were significantly increase in the group CHF compared with the group S (P < 0.01), but they were limited in the group HTEA (P < 0.01). Hypertrophy and edema, degeneration and necrosis of myocytes can be seen in rats with CHF, as well as muscle fibers disruption and collagen fiber increase, while the pathological amorphous were attenuated in HTEA rats. beta(3)AR and eNOS mRNA levels were significantly decreased in the group THEA compared with the group CHF. CONCLUSIONS: These results indicate that HTEA could ameliorate ventricular remodeling and cardiac function in rats with heart failure induced by myocardial infarction. The mechanism could involve decreases of beta(3)AR expression in rats of heart failure.

Blood homocysteine and folic acid levels may provide reference value for the treatment of sudden total frequency deafness.

BACKGROUND: The cause of sudden sensorineural hearing loss (SSNHL) is still unknown. Literature has indicated that there is a statistically significant correlation between hyperhomocysteinemia and SSNHL, yet there is lack of study in the relationship concerning total frequency deafness subtype of SSNHL. This study investigated the relationship between plasma concentration of homocysteine (Hcy), serum concentration of folic acid and occurrence and treatment responding in total frequency deafness adult patients, and explored whether targeted early intervention was associated with improved clinical outcome in this subgroup. METHODS: A total of 54 consecutive adult patients with diagnosis of sudden total frequency deafness in a single institution was enrolled into the study group. Two control groups were established. Control group 1 was derived from inpatients with normal listening comprehension. Control group 2 included 52 patients with sudden total frequency deafness treated in a parallel hospital. Blood concentration of folic acid and Hcy was investigated. Treatment included Ginkgo biloba extract, dexamethasone, hyperbaric oxygen, folic acid, vitamin B6, and optional vitamin B12. All data was statistically analyzed. Blood level of Hcy and folic acid was compared between study group and control group 1. RESULTS: Although there was no clear evidence for the divergence trend of Hcy and folic acid levels individually, the results showed that the study group had higher blood level of Hcy and lower blood level of folic acid, than control group. In the study group, 24 patients (44.44%) demonstrated treatment effectiveness after the 2-week treatment course. Patients without vertigo had higher effective rate than patients with vertigo (P<0.05). CONCLUSIONS: Effective rate of study group was higher than control group 2 which had no folic acid and vitamin B6/B12 supplement. High blood Hcy and low blood folic acid were closely associated in patients with sudden total frequency deafness. The currently accepted concept of treatment for sudden total frequency deafness is not essentially satisfactory. Testing of plasma Hcy and serum folic acid may provide referential value for its treatment and prognosis evaluation.

Clinical study on the wrist-ankle acupuncture treatment for 30 cases of diabetic peripheral neuritis.

OBJECTIVE: To study the mechanisms of wrist-ankle acupuncture for prevention and treatment of diabetic peripheral neuritis. METHODS: Ninety cases of diabetic peripheral neuritis were randomly divided into 3 groups, and treated respectively with wrist-ankle acupuncture, body-acupuncture, and the western routine medical treatment, with 30 cases in each of the groups; and therapeutic effects and laboratory results compared. RESULTS: It is proved that the therapeutic effects of the wrist-ankle acupuncture group and body acupuncture group were significantly superior to those of the control group, with no significant differences between the former two groups. CONCLUSION: Wrist-ankle acupuncture has the actions of improving the metabolisms of blood sugar and blood-lipid, lowering down blood viscosity, and restoring the functions of peripheral nerve cells, thus giving definite therapeutic effects for diabetic peripheral neuritis.

Genetic variants in de novo lipogenic pathway genes predict the prognosis of surgically-treated hepatocellular carcinoma.

Over-expression of de novo lipogenesis (DNL) pathway genes is associated with the prognosis of various types of cancers. However, effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and death of hepatocellular carcinoma (HCC) patients after surgery are still unknown. A total of 492 primary HCC patients treated with surgery were included in this study. Nine SNPs in 3 genes (ACACA, FASN and ACLY) of DNL pathway were genotyped. Multivariate Cox proportional hazard regression model and Kaplan-Meier curve were used to analyze the association of SNPs with clinical outcomes. Two SNPs in ACACA gene were significantly associated with overall survival of HCC patients. Patients carrying homozygous variant genotype (VV) in rs7211875 had significantly increased risk of death, while patients carrying VV genotype in rs11871275 had significant decreased risk of death, when compared with those carrying homozygous wild-type or heterozygous genotypes. Moreover, patients carrying VV genotype in rs11871275 had decreased recurrence risk, while patients carrying variant genotype in rs4485435 of FASN gene had increased recurrence risk. Further cumulative effect analysis showed significant dose-dependent effects of unfavorable SNPs on both death and recurrence. SNPs in DNL genes may serve as independent prognostic markers for HCC patients after surgery.

Association between leukocyte telomere length and glioma risk: a case-control study.

BACKGROUND: Compelling epidemiological evidence indicates that alterations of telomere length are associated with risks of many malignancies in a tumor-specific manner, such as lung cancer, breast cancer, and non-Hodgkin's lymphoma. However, the association between leukocyte telomere length and glioma risk has not been investigated. METHODS: Relative telomere length (RTL) of peripheral blood leukocytes from 467 glioma patients and 467 healthy controls, matched by age and sex, was measured using the real-time PCR-based method in a case-control study. An unconditional multivariate logistic regression model was applied to estimate the association between RTL and glioma risk. RESULTS: Glioma patients showed notably longer RTL than controls (median, 0.555 vs 0.444; P > .04). RTL was negatively correlated with age in both cases (ρ = -0.430; P < .001) and controls (ρ = -0.388; P < .001). After adjusting for age, sex, smoking status and family history of cancer, multivariate logistic regression analysis showed that there was a U-shaped association between RTL and glioma risk (P for nonlinearity <.001). Compared with individuals in the second tertile of RTL, the odds ratios (95% CI) for participants in the first and third tertiles were 2.16 (range, 1.52-3.09) and 3.51 (range, 2.45-5.00), respectively. Stratified analysis showed that the association between RTL and glioma risk was not modulated by major host characteristics. CONCLUSIONS: Our study demonstrates for the first time that either shorter or longer RTL in peripheral blood leukocytes is associated with increased glioma risk, which warrants further investigation in the future.

[The ocular optic fiber used in the endoscopic sinus surgery of dacryocystorhinostomy in the treatment of chronic dacryocystitis and recurrent dacryocystitis].

OBJECTIVE: To explore a method for locating the area of lacrimal sac in dacryocystorhinostomy under endoscopy. METHOD: Sixty-eight patients were performed dacryocystorhinostomy under endoscopy. Take light spot of ocular optic fiber as the lacrimal sac projection to the lateral wall of the nasal cavity position. RESULT: With the guiding of ocular optic fiber, lacrimal sac can be located accurately. The operating time of dacryocystorhinostomy under endoscopy was shortened significantly, and the operation procedure was simplified. All patients were followed up for 2 years, only 2 recurrent cases were found. The success rate reach to 97.06% (66/68). CONCLUSION: Ocular optical fiber used in locating the lacrimal sac in dacryocystorhinostomy under endoscopy is simple and feasible, and can be widely used.

[A clinical study of dacryocystorhinostomy per nasal endoscope guided by endo-ophthalmic optical fiber].

OBJECTIVE: To get a method of dacryocyst allocation for dacryocystorhinostomy per nasal endoscope. METHOD: The dacryocyst of 7 chronic dacryocystitis cases(8 eyes) were located through nasal cavity guided by endo-ophthalmic optical fiber. RESULT: All the 7 patients got successful operations, the bleeding was 10-20 ml during the operation , postoperative recovery was good, no infection occurred. Five patients received operations twice, all of them were detained anaesthetic tubes for 3 to 6 months, dacryocyst rinsing were conducted once per month after extubation. No obstructions and complications occurred after one year follow up. CONCLUSION: Endo ophthalmic optical fiber can be used to locate dacryocyst in dacryocystorhinostomy per nasal endoscope.

[Protective effect of estrogens replacement on apoptosis cells of nasal mocosas in ovariectomized rats].

OBJECTIVE: To study the protective effect of nylestriol on apoptosis cells of atrophic nasal mucosas in ovariectomized rats and the difference between nasal drip and gastrogavage. METHOD: Sixty rats with atrophic rhinitis were divided into four groups at random (each with 15 rats): contrary group (Cg), ovariectomized group (Og), ovariectomized + nylestriol nasal drip group (ONNDg), and ovariectomized + nylestriol by gastrogavage (ONGg). Earlier apoptosis cells of nasal mucosas taken from nasal septum were measured with flow cytometry. RESULT: After being ovariectomized, the number of apoptosis cells of mucosas increased. In ONGg, the number of apoptosis cells of mucosas increased at 15 d after operation (P < 0.05), but it recovered at 30 d and 60 d after operation. In ONGg, the number of apoptosis cells of mucosas increased at 15 d and 30 d after operation (P < 0.05), but it recovered at 60 d after operation. CONCLUSION: Estrogen replacement by gastrogavage and via nasal drip have effects on protecting cells of mucosas from lacking of estrogen by decreasing apoptosis cells in ovariectomized rats. It might cost more time to get therapeutic effectiveness via nasal drip than by gastrogavage.