In recent years， the research method of Mendelian randomization based on genome-wide association studies has been widely used for etiological exploration in the medical field， which can effectively overcome the confounding biases and interference of reverse causalities in traditional observational researches with its unique advantages of the distributive randomness and timing priority of genetic variants. This article reviews the method of Mendelian randomization and its application in liver cancer， in order to provide new ideas for the research on causal association in liver cancer.

Objective:To compare the differences in prefrontal activation patterns between major depressive disorder and schizophrenia during the eye basic emotion discrimination task (EBEDT).Methods:Using functional near infrared spectroscopy (fNIRS) technology and block design, the changes of prefrontal lobe oxyhemoglobin (Oxy-Hb) concentrations under EBEDT in 40 patients with major depressive disorder, 47 patients with schizophrenia and 55 normal controls were compared. Subsequently, employing years of education as a covariate, an analysis of covariance was performed on the EBEDT behavioral results and the changes in prefrontal Oxy-Hb concentrations in the three groups.The statistical software was SPSS 25.0.Results:(1)The correct number of EBEDT in schizophrenia group (13.93±7.67) was significantly lower than that in major depressive disorder group (19.26±8.07) and normal control group (21.79±6.36)(both P<0.05), and the EBEDT reaction time in schizophrenia group ((3.97±1.77) s) was significantly longer than those in major depressive disorder group ((3.21±1.27) s) and normal control group ((2.63±0.62) s)(both P<0.05).(2)During the EBEDT task block, the normal control group showed increased activation levels in the frontal polar region, Broca's area, anterior motor cortex and supplementary motor area (SMA) compared with the control block( t=2.02-3.18, all P<0.05); and the schizophrenia group showed increased activation levels in the frontal eye field compared with the control block( t=2.26, P=0.03); while the major depressive disorder group exhibited decreased activation levels in the entire prefrontal lobe compared with the control block( t=-3.47--2.34, all P<0.05). (3)During the emotion recognition task of EBEDT, the activation levels of the frontal polar area (ch37), dorsolateral prefrontal cortex (ch31), Broca's area (ch49, ch51, ch53), and SMA (ch1, ch47, ch52) were significantly different among the major depressive disorder, schizophrenia and normal controls( F=3.23-5.53, all P<0.05). Further pairwise comparisons showed that the activation levels in all the above pathways were lower in the major depressive disorder group than those in the normal control group, and the activation levels in Broca's area (ch53) and SMA area (ch52) were lower in the schizophrenia group than those in the normal control group, while the activation levels in the frontal polar area (ch37) and Broca's area (ch49) were lower in the major depressive disorder group than those in the schizophrenia group(all P<0.05). Conclusions:In EBEDT, the activation patterns of the prefrontal cortex are different between patients with major depressive disorder and patients with schizophrenia. Patients with major depressive disorder have a decrease in prefrontal cortex activation, while patients with schizophrenia have an increase in the frontal eye field activation.The activation levels in prefrontal cortex of both patients group are lower than that of normal controls. Meanwhile, the prefrontal cortex activation level of patients with major depressive disorder is lower than that of patients with schizophrenia.

The spectrum of biopsy-confirmed kidney disease varies with regions and periods. We describe the distribution of pathological types and epidemiological characteristics of kidney diseases in Northwest China due to regional differences in geographical environment, social economy, and dietary habits. Methods: Kidney biopsy cases from 2005 to 2020 in Xijing Hospital were retrospectively analyzed. Pathological characteristics of patients in different periods were analyzed using the t test or chi-square test. Joinpoint regression was used to analyze trends in pathological types and disease spectrum. Results: A total of 10,528 eligible patients were included. Primary glomerular disease (PGD) accounted for the majority of the cases and exhibited an obvious downward trend, whereas secondary glomerular disease (SGD) showed an obvious upward trend. Among PGD, immunoglobulin A nephropathy (IgAN) remained the most common pathological type, and the detection rate of membranous nephropathy (MN) was significantly increased. Among SGD, Henoch-Schönlein purpura nephritis (HSPN) was the most common pathological type and may present a significant characteristic of Northwest China. Diabetic nephropathy (DN) exhibited the most obvious upward trend in the whole process, whereas the fastest growth since 2012 was in hypertensive nephropathy. Conclusion: The proportion of SGD increased whereas PGD declined. IgAN remained the most common PGD, and HSPN was the most common SGD. MN and DN showed the most obvious upward trend among PGD and SGD, respectively. Changes in the spectrum of kidney disease, especially the constituent ratio of SGD, pose a great challenge to public health.

Objective:To explore the effect of autologous fat transplantation based on the fine anatomy of the female perineum and aesthetic standards.Methods:From June 2015 to September 2020, 25 female patients with perineal cosmetology requirements in the Department of Plastic Surgery, the Fourth Affiliated Hospital of Harbin Medical University, aged from 28 to 55 years, with an average of 33.7 years. 50-80 ml of the patient＇s autologous fat were collected and filled according to the perineal anatomy and aesthetic standards. Postoperative anti-inflammatory treatment was implemented and sexual life was forbidden for 2 weeks.Results:25 patients were satisfied with the filling effect immediately after operation. Follow-up for 7 days, 1, 3, and 6 months after operation, 20 of 21 cases underwent pudendal filling operation were very satisfied with the postoperative morphology, and 1 case was less satisfied. Among the 20 cases underwent vaginal filling and labia major filling, 17 cases were very satisfied with the postoperative morphology, 2 cases were satisfied after the operation, and 1 case was less satisfied. Of the 10 cases underwent vaginal and G-spot injection, 6 cases were satisfied after the operation. The morphology was very satisfactory, 2 cases were more satisfactory, and 2 cases were less satisfactory. According to a survey of 25 cases of postoperative sexual life satisfaction, 19 cases (76%) had a significant improvement in their conscious sexual life, 3 cases had a more obvious improvement, 1 case had less improvement, and 2 cases had no conscious improvement.Conclusions:The autologous fat injection based on the fine anatomy and aesthetics of the perineum can significantly improve the aesthetic appearance of the perineum.

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.

AIM: To observe the influence of gold nanoparticles combined with Endostar (AuNPs-Endostar) on the melanoma lung metastasis of mice and the underlying mechanism.METHODS: C57BL/6 mice (n=24) were selected for constructing the model of spontaneous lung metastasis of melanoma B16-F10 cells.Subsequently, the mice were randomly divided into Endostar group, AuNPs group, AuNPs-Endostar group and model group.After the formation of melanoma, the mice in each group were injected with different drugs through tail vein for 0.1 mL daily.After 9 d, the mice were narcotized for cutting the tumors in situ.After the operation, they were raised for 2 weeks before killed for obtaining the lung tissues to observe the situation of the metastasis.HE staining was utilized for observing the necrosis status of the tumors in situ, while immunostaining was applied for testing the expression of CD31, carbonic anhydrase-IX (CA-IX), vimentin and zonula occludens-1 (ZO-1) in the tumors.RESULTS: Compared with model group, the pulmonary metastasis in the groups with medical treatment was obviously reduced.In AuNPs-Endostar group, the metastasis inhibition rate was the highest, and the tumor necrosis was also decreased obviously, with the significant reduction of CD31, CA-IX and vimentin expression in the tumors and significant increase in ZO-1 expression.CONCLUSION: Compared with using Endostar or AuNPs alone, the combination of AuNPs with Endostar significantly improves the curative effect of inhibiting the pulmonary metastasis of melanoma in the mice.The mechanism may be related to reducing the tumor angiogenesis, norma-lizing the blood vessels and improving tumor hypoxia, thus inhibiting the tumor epithelial-mesenchymal transition, increasing the tight junctions between tumor cells and decreasing the invasiveness.

According the current National standard for laboratory animal, herpes B virus antibody must be tested and negative for all the breed/tested macaques,howere,in fact the positive rate is around 60-70% in breeding colony. Being the National Standard, if it is too far from the reality of the filed, weighing and changing should be made.Hardness/crispness degree of laboratory animal diet never been considered as a listed value in the National Standard for Laboratory Animal to identify the quality of diet.In fact, this index affects a lot about daily diet intake and physiological status of laboratory animals.Hereby, the authors suggest to take the index into the National Standard, to assess the quality of laboratory animal diet in a more comprehensive way.

AIM:To investigate whether gold nanoparticles (GNPs) reverses adriamycin (ADM), resistance of human hepatocellular carcinoma drug-resistant cell line HepG2/ADM and to explore the potential mechanism.METH-ODS:The sensitivities of HepG2 cells and HepG2/ADM cells to ADM were tested by MTT assay before and after GNPs pretreatment.The apoptotic rate was examined by flow cytometry.The concentration of ADM in HepG2/ADM or HepG2 cells was determined by ultraviolet-visible spectrophotometer .The content of glutathione ( GSH ) in HepG2/ADM or HepG2 cells by DTNB method.RESULTS:The half maximal inhibitory concentrations ( IC50 ) of ADM for HepG2/ADM cells were(29.46 ±1.73) mg/L and (15.18 ±0.85) mg/L before and after GNPs pretreatment,respectively.The IC50 of ADM for HepG2 cells was (9.16 ±2.03) mg/L before pretreatment.The apoptotic rate in GNPs+ADM group was higher than that in ADM group ( P<0.05 ) .The concentration of ADM in HepG2/ADM group was lower than that in HepG2 group (P<0.01).After GNPs pretreatment, the concentration of ADM in HepG2/ADM cells was higher than that before pretreatment.The content of GSH in HepG2/ADM group was higher than that in HepG2 group (P<0.01).After GNPs pretreatment, the content of GSH in the HepG2/ADM cells was lower than that before pretreatment.CONCLUSION:Gold nanoparticles can reverse ADM resistance of human hepatocellular carcinoma drug-resistant cell line HepG2/ADM,
reduce the content of GSH and increase the concentration of ADM in HepG2/ADM cells.

Objective To investigate the emergency treatment measures of spontaneous frontotemporal intracerebral hematoma.Methods Retrospectively analyzed the rescue process and surgical experiences of 27 patients with spontaneous frontotemporal intracerebral hematoma combined with subarachnoid hemorrhage or ventricular hemorrhage.Twenty-three cases underwent surgery;4 cases with cerebral hernia under general anesthesia underwent craniotomy hematoma clearance,aneurysm clip and decompressive craniectomy;7 cases with previous history of hypertension,considered with hypertensive intracerebral hemorrhage,was performed with craniotomy hematoma clearance and decompressive craniectomy in the emergency under general anesthesia; 12 cases of middle cerebral artery aneurysms bleeding,chosen craniotomy hematoma clearance and aneurysm clip;4 cases found nothing by digital subtraction angiography (DSA) or CT angiography (CTA),were given conservative treatment,one of them was found arteriovenous malformations after 1 month,which was treated by γ-ray.Results After the surgery,2 cases died due to severe cerebral infarction,25 cases were followed up for 6 months,according to the Glasgow outcome scale(GOS) classification:17 cases with good prognosis,7 cases with poor prognosis,1 case with vegetative state.Conclusions Cerebral hernia formation in patients with spontaneous frontotemporal intracerebral hematoma should relieve cerebral hernia and mass effect as soon as possible,early surgery to save lives.Which of them without brain hernia,after diagnosis by CTA or DSA,choice suitable treatment.Sufficient preoperative evaluation,suitable surgical timing and good microsurgical techniques can improve the prognosis.