Objective To explore the value of high-frequency ultrasound in the detection of metastatic hepatocellular carcinoma and displaying lesion characteristics. Methods A total of 38 paitients with hepatocellular carcinoma satellite lesions within 40 mm of subcutaneous tissue were underwent low-frequency (1-5 MHz) and high-frequency (6-9 MHz) ultrasound. Detection rates and ultrasonic features were compared. Results High-frequency grayscale ultrasound had a higher detection rate (71.1% vs. 36.8%, P＜0.001). Subgroup analysis showed higher detection rates with chemotherapy history (88.9% vs. 33.3%, P＝0.002), fatty liver (71.9% vs 31.3%, P＜0.001) or superficial lesion (within 20 mm, 76.5% vs 41.2%, P＝0.031). High-frequency ultrasound also showed clearer margins (P＝0.004) and more arterial-phase rim enhancement (P＝0.007). Conclusions 6-9 MHz ultrasound detects metastatic hepatocellular carcinoma, especially superficial lesions, more effectively than 1-5 MHz ultrasound and better visualizes characteristics.

Objective:We aimed to investigate the relationship between CYP2D6*10 gene polymorphisms and adverse reactions associated with tamoxifen treatment in breast cancer patients, and assess the value of CYP2D6*10 gene polymorphism testing in guiding the use of medications in endocrine therapy for breast cancer.Methods:177 breast cancer patients with HR-positive and postoperative tamoxifen were admitted to the First Affiliated Hospital of Nanjing Medical University from November 2012 to December 2021. Their clinicopathologic data were collected for follow-up observation of adverse reactions related to tamoxifen treatment. After two years of tamoxifen treatment, finger blood of these patients was taken for CYP2D6 gene polymorphism detection. Moreover, databases including RNAfold, QTLbase, 3DSNP v2.0, RegulomeDB 2.2, and HaploReg v4.2 were used to predict the annotation of proximal and distal interactions of CYP2D6 polymorphic sites between genes and regulatory elements.Results:Genotyping analysis revealed 40 patients (22.6%) with the CC genotype, 79 (44.6%) with the CT genotype, and 58 (32.8%) with the TT genotype. Common adverse reactions to tamoxifen included abnormal liver function (58), fatty liver (81), uterine fibroids (12), and endometrial surgery for endometrial thickening (17). Univariate and multivariate logistic regression analyses showed that there were no significant statistical differences between the CC and CT+TT genotypes in terms of liver damage, new-onset fatty liver, uterine fibroids, or tumor recurrence and metastasis ( P＞0.05). Notably, endometrial thickening was more significant in patients with the CT+TT genotype (4.37±3.82 mm) than in those with the CC genotype (2.43±2.96 mm), with a statistically significant difference between them ( P＜0.01). Bioinformatic analysis suggested that in breast tissues, the CYP2D6*10 polymorphic locus had a significant expression quantitative trait locus (eQTL) effect with CYP2D6, and its genetic variations could affect the binding of CYP2D6 to transcription factors, which might modulate the expression of CYP2D6 through changes in secondary structure and chromatin modifications, etc., and thus affect the tamoxifen drug sensitivity. Further eQTL analysis showed significant correlation between CYP2D6 expression levels with different genotypes of the CYP2D6 rs1065852 polymorphism in breast tissues ( P＜0.01). Conclusion:Tamoxifen remains a primary therapeutic agent for premenopausal HR-positive breast cancer patients, and its efficacy is influenced by polymorphisms in the CYP2D6*10. It is recommended that for breast cancer patients carrying the CYP2D6 CT and TT genotypes, endometrial monitoring should be strengthened during treatment with tamoxifen, and the medication should be adjusted in a timely manner.

Objective To investigate the regulatory role and mechanism of mitochondrial riboso-mal protein S35(MRPS35)in the proliferation,invasion,and migration of colon cancer cells.Meth-ods A total of 120 colon cancer tissues and adjacent normal tissues from patients undergoing radical resection for colon cancer were collected.Human colon cancer cell lines(HCT116,SW480,SW620)and a human normal colon epithelial cell line(NCM460)were cultured.Bioinformatics analysis,real-time quantitative polymerase chain reaction,Western blot,immunohistochemical(IHC)analysis,and cellular functional experiments(plate clone formation assay,scratch test,Transwell migration assay,CCK-8 cell viability assay)were conducted to evaluate the expression and regulatory mechanism of MRPS35 in colon cancer.Results Bioinformatics analysis showed that the expression level of the MRPS35 gene was higher in colorectal cancer tissues than in adjacent normal tissues(P＜0.05).The relative expression levels of MRPS35 mRNA and MRPS35 protein were higher in human colon cancer cell lines(HCT116,SW480,SW620)than in NCM460 cells(P＜0.05).The relative ex-pression level of MRPS35 protein was higher in colon cancer tissues than that in adjacent normal tis-sues(P＜0.05).The expression level of MRPS35 was significantly correlated with tumor diameter,tumor differentiation,and T stage(P=0.002,0.021,0.036).Patients with high MRPS35 expres-sion had a higher overall survival rate than those with low MRPS35 expression(Log-rank P=0.015).After knockdown of MRPS35,the abilities of colon cancer cell cloning,proliferation,invasion,and migration were significantly enhanced.Furthermore,the expression of Wnt1,β-Catenin,and their downstream target proteins increased significantly after MRPS35 knockdown.Conclusion MRPS35 is significantly overexpressed in both colon cancer tissues and colon cancer cells,and it may inhibit the occurrence and development of colon cancer by regulating the Wnt/β-Catenin signaling pathway.Therefore,MRPS35 has the potential to become a novel biomarker and therapeutic target for colon cancer.

Objective:We aimed to investigate the relationship between CYP2D6*10 gene polymorphisms and adverse reactions associated with tamoxifen treatment in breast cancer patients, and assess the value of CYP2D6*10 gene polymorphism testing in guiding the use of medications in endocrine therapy for breast cancer.Methods:177 breast cancer patients with HR-positive and postoperative tamoxifen were admitted to the First Affiliated Hospital of Nanjing Medical University from November 2012 to December 2021. Their clinicopathologic data were collected for follow-up observation of adverse reactions related to tamoxifen treatment. After two years of tamoxifen treatment, finger blood of these patients was taken for CYP2D6 gene polymorphism detection. Moreover, databases including RNAfold, QTLbase, 3DSNP v2.0, RegulomeDB 2.2, and HaploReg v4.2 were used to predict the annotation of proximal and distal interactions of CYP2D6 polymorphic sites between genes and regulatory elements.Results:Genotyping analysis revealed 40 patients (22.6%) with the CC genotype, 79 (44.6%) with the CT genotype, and 58 (32.8%) with the TT genotype. Common adverse reactions to tamoxifen included abnormal liver function (58), fatty liver (81), uterine fibroids (12), and endometrial surgery for endometrial thickening (17). Univariate and multivariate logistic regression analyses showed that there were no significant statistical differences between the CC and CT+TT genotypes in terms of liver damage, new-onset fatty liver, uterine fibroids, or tumor recurrence and metastasis ( P＞0.05). Notably, endometrial thickening was more significant in patients with the CT+TT genotype (4.37±3.82 mm) than in those with the CC genotype (2.43±2.96 mm), with a statistically significant difference between them ( P＜0.01). Bioinformatic analysis suggested that in breast tissues, the CYP2D6*10 polymorphic locus had a significant expression quantitative trait locus (eQTL) effect with CYP2D6, and its genetic variations could affect the binding of CYP2D6 to transcription factors, which might modulate the expression of CYP2D6 through changes in secondary structure and chromatin modifications, etc., and thus affect the tamoxifen drug sensitivity. Further eQTL analysis showed significant correlation between CYP2D6 expression levels with different genotypes of the CYP2D6 rs1065852 polymorphism in breast tissues ( P＜0.01). Conclusion:Tamoxifen remains a primary therapeutic agent for premenopausal HR-positive breast cancer patients, and its efficacy is influenced by polymorphisms in the CYP2D6*10. It is recommended that for breast cancer patients carrying the CYP2D6 CT and TT genotypes, endometrial monitoring should be strengthened during treatment with tamoxifen, and the medication should be adjusted in a timely manner.

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.

【Objective】 To investigate the protective effect and mechanism of platelet-rich plasma (PRP) on lipopolysaccharide (LPS) -induced inflammatory response in BV2 cells. 【Methods】 BV2 microglia were divided into normal control group, 10%PRP control group, LPS group (LPS induction), 3%PRP+ LPS group (LPS induction, 3%PRP pretreatment), 5%PRP+ LPS group (LPS induction, 5%PRP pretreatment), 10%PRP+ LPS group (LPS induction, 10%PRP pretreatment), and the proliferation of BV2 cells was measured by CCK-8. The mitochondrial membrane potential of BV2 cells was measured by confocal microscopy, ROS was measured by fluorescence method, and NO was measured by Griess method. The protein expressions of IL-6, TNF-α, BACH1, GPX4, NRF2 and HO-1 were detected by Western blot. In addition, BV2 microglia were treated with HO-1 inhibitor and divided into normal control group, LPS group, ZnPP+ LPS group, 10%PRP+ LPS group, ZnPP+ LPS+ 10%PRP group, and the protein expressions of HO-1, IL-6 and TNF-α were detected by Western blot. 【Results】 Compared with normal control group, PRP promoted the proliferation of BV2 cells (P<0.01). The mitochondrial membrane potential decreased, ROS production increased, the levels of NO, IL-6, TNF-α and BACH1 increased (P<0.01). However, the expression levels of GPX4, NRF2 and HO-1 decreased (P<0.01) in LPS group. Compared with LPS group, the proliferation activity and mitochondrial membrane potential of BV2 cells in 3%PRP+ LPS, 5%PRP+ LPS and 10%PRP+ LPS groups significantly increased. The levels of ROS, NO, IL-6, TNF-α and BACH1 significantly decreased (P<0.01). The expressions of GPX4, NRF2 and HO-1 in different concentrations of PRP (3%, 5% and 10%) increased (P<0.01). Moreover, the expression of IL-6 and TNF-α in ZnPP+ LPS group was significantly higher than that in LPS group after HO-1 inhibitor treatment. Compared with 10%PRP+ LPS+ ZnPP group, HO-1 inhibitor could reverse the effect of PRP on the expression of IL-6 and TNF-α in LPS-induced BV2 cells (P<0.01). 【Conclusion】 PRP inhibits the inflammatory response of BV2 microglia induced by LPS by activating the NRF2/HO-1 signaling pathway.

Objective This paper introduces the research progress on the pathogenesis of depression related to gut microbiota and provides the resources for the subsequent development of antidepressant drugs targeting gut microbiota. Methods 33 literatures on gut microbiota and depression in recent years were reviewed. The changes of gut microbiota diversity under depression were discussed from the perspectives of phylum, family and genus. The relationship between gut microbiota and the pathogenesis of depression was expounded at the molecular level, and the existing relevant studies were summarized. The feasibility of drug development targeting gut microbiota was explored. Results There is a relationship between gut microbiota disorder and depression. Existing biological agents such as probiotics can alleviate depression by adjusting the disorder of gut microbiota. Conclusion The imbalance of gut microbiota is closely related to the occurrence of depression, and the development of drugs targeting gut microbiota may become a new way to treat depression.

Objective:To systematically evaluate the effect of hydrocortisone combined with vitamin C and vitamin B1 on the efficacy of patients with sepsis or septic shock.Methods:Databases including CNKI, Sino Med, VIP, Wanfang, PubMed, the Cochrane Library, and Embase were searched from inception to January 2021 for the randomized controlled trial (RCT) about hydrocortisone combined with vitamin C and vitamin B1 to treat sepsis or septic shock. The experimental group was given intravenous injection of hydrocortisone, vitamin B1 and vitamin C based on conventional treatment; the control group was given conventional treatment or placebo/hydrocortisone/hydrocortisone+vitamin B1 based on conventional treatment. Outcome indicators included sequential organ failure assessment (SOFA), mortality, the duration of vasoactive drugs, new acute kidney injury (AKI) patients, length of stay in intensive care unit (ICU) and in hospital. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.3 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 6 articles involving 816 patients were included, with 411 patients in the experimental group and 405 patients in the control group. The Meta-analysis results showed that the duration of vasoactive drugs in the experimental group was significantly shorter than that in the control group [mean difference ( MD) = -24.02, 95% confidence interval (95% CI) was -32.36 to -15.68, P < 0.000 01]. However, there were no significant differences in SOFA, mortality, new AKI patients, the length of ICU stay and hospital stay between the two groups [SOFA: MD = -0.14, 95% CI was -1.15 to 0.87, P = 0.79; mortality: relative risk ( RR) = 0.99, 95% CI was 0.81 to 1.21, P = 0.92; new AKI patients: RR = 1.10, 95% CI was 0.42 to 2.87, P = 0.84; length of ICU stay: MD = 1.33, 95% CI was -2.22 to 4.89, P = 0.46; length of hospital stay: MD = 1.02, 95% CI was -0.66 to 2.69, P = 0.23]. The funnel plot showed that most of the points were symmetrical and showed an inverted funnel shape, suggesting that the publication bias among the studies was small. There was no significant publication bias on this Meta-analysis. Conclusions:Hydrocortisone combined with vitamin C and vitamin B1 can shorten the duration of vasoactive drugs in patients with sepsis or septic shock, but it cannot effectively reduce the SOFA score, mortality, new AKI patients, length of stay in ICU and in hospital. Limited by the number and quality of the included studies, further large-scale, multi-center, blinded, RCT are still needed for verification.

Objective    To summarize the individualized selection of surgical treatment strategies and the key points of perioperative management for patients with heart valve disease complicated with severe chronic heart failure. Methods    The clinical characteristics of 5 male patients with valvular heart disease complicated with severe chronic heart failure (CHF) were analyzed retrospectively from June 2017 to October 2018 in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, with an average age of 60.21 years. Results    Five patients were given angiotensin receptor and neprilysin inhibitor (ARNI)-based anti-heart failure treatment after admission. The operation mode of these patients was decided to be valve replacement under cardiopulmonary bypass after individualized evaluation of patients’ improving symptoms. Three patients were treated with intra-aortic balloon pump (IABP) and continuous renal replacement therapy (CRRT) early after operation to assist patients in improving cardiac function. Five patients recovered oral anti-heart failure after awakening. All patients were discharged smoothly 2 weeks after operation. Conclusion    Individualized evaluation is needed for the choice of operation timing and mode, standardized preoperative treatment for heart failure, shortening the aortic blocking time during cardiopulmonary bypass, and early application of left ventricular adjuvant drugs or instruments are all important measures to help patients recover smoothly.

Objective To summarize the characteristics and management of pregnancy complicated with aortic dissection, and to explore the reasonable diagnosis and treatment plan. Methods The clinical data of 10 patients of pregnancy complicated with aortic dissection in Wuhan Tongji Hospital from January 2011 to June 2017 were collected. Their age was 25.2 (21-29) years. Results In the 10 patients, the majority (8 patients) were primipara, and most of them were in the late stages of pregnancy (5 patients) and puerperal (4 patients). Among them, 1 patient had gestational hypertension, and the blood pressure of the left and right upper extremities was significantly abnormal (initial blood pressure: left upper limb blood pressure: 90/60 mm Hg, right upper limb blood pressure: 150/90 mm Hg). The major clinical manifestations were severe chest and back pain which happened suddenly, with D-dimmer and C-creative protein increased which may be associated with inflammatory reaction. All patients were diagnosed by thoracoabdominal aortic CTA, including 5 patients of Stanford type A dissection and 5 patients of Stanford type B dissection. In the 10 patients, 1 patient refused surgery and eventually died of aortic rupture with the death of fetus before birth. And the remaining 9 patients underwent surgical treatment, 3 patients of endovascular graft exclusion for thoracic aortic stent graft, 2 patients underwent Bentall operation, 1 patient with Bentall + total aortic arch replacement + vascular thoracic aortic stent graft, 1 patient with Bentall operation combined with endovascular graft exclusion for thoracic aortic stent graft, 1 patient with Bentall + coronary artery bypass grafting, 1 patient of thoracoabdominal aortic vascular replacement. Among them, 1 patient underwent endovascular graft exclusion for thoracic aortic stent graft died of severe postoperative infection, and the remaining 8 patients were discharged from hospital. Nine patients were single birth, among them 5 newborn patients had severe asphyxia, 4 patients had mild asphyxia. Finally, 3 neonates died of severe complications, and the remaining 6 survived. Conclusion The ratio of pregnancy with Stanford type A aortic dissection is far higher than in the general population, the possibility of fetal intrauterine asphyxia is larger, but through active and effective surgical and perioperative treatment, we can effectively save the life of mother and fetus.