Clinical management strategies for recipients with renal graft loss / 器官移植

With the maturity of kidney transplantation, introduction of new immunosuppressive drugs and improvement of immunosuppressive regimen, the short-term survival rate of kidney transplant recipients has been significantly improved, whereas the long-term survival rate has not been significantly elevated. Kidney transplant recipients may have the risk of renal graft loss. Clinical management after renal graft loss is complicated, including the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy. These management procedures directly affect clinical prognosis of patients with renal graft loss. Nevertheless, relevant guidelines or consensuses are still lacking. Clinical management of patients after renal graft loss highly depend upon clinicians’ experience. In this article, the adjustment of immunosuppressive drugs, management of renal graft and selection of subsequent renal replacement therapy were reviewed, aiming to provide reference for prolonging the survival and improving the quality of life of these patients.

Distinction and processing of common artifact in clinical visual electrophysiology / 中华实验眼科杂志

Objective:To explore the common causes and solutions for artifacts in clinical visual electrophysiological examination.Methods:A cross-sectional study was performed.The clinical visual electrophysiological examination results of 25 001 cases were collected from 2012 to 2020 at the Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University). Artifacts were identified and analyzed according to the standard waveform provided by the International Society for Clinical Electrophysiology of Vision.The characteristics and causes of the artifact were analyzed.The solutions to reduce and eliminate the artifact were proposed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University) (No.KY2020053).Results:There were 60 typical artifacts identified among the 25 001 cases.Common causes of the artifacts were classified as three categories, the factors related to subjects, environment, or instruments.Among the 60 cases, 42(70.0%) were caused by tension in head and facial muscles of patients, 9(15.0%) due to blinking of patients, 4(6.7%) resulted from 50 Hz power frequency artifact, 2(3.3%) arisen from abnormal amplifier, and 3(5.0%) for other reasons.The strategies to avoid artifact were as follows.First, examiners could inform patients of the examination process in advance to help patients to relax and avoid the influencing factors, such as muscle tension in head and face, blinking, inattention and so on; second, high-quality 50 Hz hardware wave trap was recommended to reduce 50 Hz artifact, with good ground connection and removing of the high-power electrical appliances near the visual electrophysiological instrument; third, clean the skin sufficiently to reduce the reference electrode impedance to less than 1 kΩ.Conclusions:There is a variety of artifact waveforms and causes.The technicians should make correct judgments and handle the artifact in time to provide more accurate examination results.The doctors should know about artifact, which is helpful for better interpretation of visual electrophysiological examination reports.

Advances in Mechanotransduction Pathway of Macrophage / 医用生物力学

Mechanical stimulation in micro-environment ( such as matrix stiffness, surface topography, cyclical stretch) can be perceived by macrophages through receptors on cell membrane, transmitted to the nucleus along the adhesion protein molecular chain and cytoskeleton, and also converted into biochemical signal to stimulate gene transcription. Mechanical stimulation drives various biological functions in macrophages, such as adhesion, proliferation, migration, and polarization, thereby playing a corresponding role in disease progression and tissue regeneration. This study demonstrates the role of micro-environment mechanics in macrophages polarization and function, and elucidates the related mechanism of mechanotransduction pathway in macrophages, so as to provide molecular biomechanics insights into the development of macrophage-targeting immunomodulatorybiomaterials.

Preliminary experience of gasless transoral vestibular robotic thyroidectomy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P25, P75), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.

Effects of umbilical moxibustion on phobic behavior and monoamine neurotransmitters in stress-model rats / 中国针灸

OBJECTIVE@#To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior.@*METHODS@#Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined.@*RESULTS@#Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group.@*CONCLUSION@#Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.

The value of peripheral blood and pleural effusion T-SPOT.TB combined with pleural effusion adenosine deaminase in diagnosis of tuberculous pleurisy / 中国热带医学

@#Abstract: Objective To explore the relationship between peripheral blood and pleural effusion tuberculosis (TB) infection effector T cells, and to further evaluate the value of combined pleural effusion adenosine deaminase (ADA) for rapid diagnosis of tuberculous pleurisy. Methods The test data of 80 cases of tuberculous pleurisy and 70 cases of nontuberculous pleurisy treated in the Sixth People's Hospital of Nantong City from January 2017 to December 2020 were analyzed. The TBinfected effector T cells were also detected simultaneously in the peripheral blood and the pleural effusion by the T-SPOT technique, and the pleural effusion ADA was detected by the rate method. The subject operating characteristic curve (ROC) was applied to take the optimal pleural effusion ADA threshold to compare the sensitivity and specificity of different critical values. Person phase analysis was applied to analyze the correlation between peripheral blood and pleural effusion T-SPOT.TB. Data of peripheral blood, pleural effusion T-SPOT.TB and ADA were integrated. Results When pleural effusion ADA>45 U/L, the sensitivity and specificity for the diagnosis of tuberculous pleurisy were 50.0% and 94.3%, respectively; when ADA > 25.15 U/ L, the sensitivity and specificity were 80.0% and 72.9%. When ADA > 45 U / L, pleural/ blood T-SPOT.TB spot ratio (spot forming cells, SFCs) > 2 times, the specificity for the diagnosis of tuberculous pleurisy was 100% (highest); when 25.15 U/L< pleural effusion ADA ≤ 45 U/L, pleural/blood T-SPOT.TB spot ratio > 2 times, the specificity for the diagnosis of tuberculous pleurisy was 92.3% (second). When pleural effusion ADA ≤ 25.15 U/L, and the pleural effusion/blood T-SPOT.TB spot number ratio > 2 times, with 83.3% specificity (the lowest of the three groups). Conclusions The level of pleural effusion ADA is one of the most used methods for diagnosing tuberculous pleurisy. Further combination of pleural effusion and blood T-SPOT.TB, if the ratio of pleural effusion / blood T-SPOT. TB spots is greater than 2 times, it can further improve the diagnosis rate of tuberculous pleurisy.

The role of mammalian target of rapamycin inhibitor in virus infection of organ transplant recipients / 器官移植

At present, mammalian target of rapamycin (mTOR) inhibitors are commonly-used immunosuppressive drugs after organ transplantation, including sirolimus (rapamycin) and everolimus. mTOR inhibitors not only exert an immunosuppressive effect by inhibiting T cell proliferation, but also possess multiple potential functions, such as antiaging, anti-tumor and anti-virus infection, etc. Virus infection is one of the most common complications after organ transplantation. Current anti-viral treatments are limited and yield poor efficacy. In this article, the role of mTOR pathway in virus infection, the mechanism of common mTOR inhibitors and the role of mTOR inhibitors in different types of virus infections were reviewed, aiming to provide reference for clinical application and subsequent research of mTOR inhibitors in organ transplant recipients.

Effect of home visit based on empowerment education on psychotic symptoms， self-management ability and well-being of schizophrenia patients in home rehabilitation / 四川精神卫生

ObjectiveTo explore the effect of home visit based on empowerment education on psychotic symptoms， self-management ability and well-being of schizophrenia patients in home rehabilitation. MethodsA total of 87 cases of schizophrenia patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） and were recovering at home in Caiba town， Yibin city from January to July 2021 were selected by random sampling method as research subjects. They were divided into experimental group （n=43） and control group （n=44） according to the random number table method. The two groups received routine family visits， and the experimental group received family visits based on empowerment education. The intervention cycle of the two groups was 6 months. Before and after the intervention， the severity of psychotic symptoms， self-management ability and well-being of the patients in the two groups were assessed with the Brief Psychiatric Rating Scale （BPRS）， the Schizophrenia Self-Management Instrument Scale （SSMIS） and the Index of Well-Being Scale （IWB）. ResultsAfter intervention， the intra group comparison showed that the BPRS score in the experimental group was lower than that before the intervention （t=4.550， P<0.01）， the SSMIS scores in both groups were higher than those before intervention （t=-17.107， -6.367， P<0.01）， and the IWB score in the experimental group was higher than that before intervention （t=-9.239， P<0.01）. The comparison between groups showed that the BPRS score of the experimental group was lower than that of the control group， and the SSMIS and IWB scores were higher than those of the control group （t=-3.899， 10.564， 9.690， P<0.01）. ConclusionThe implementation of family visit based on empowerment education may help to improve the psychotic symptoms of home rehabilitation schizophrenia， and improve their self-management ability and well-being.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Research progress and application of donor-derived cell-free DNA in diagnosis and treatment of kidney transplantation / 器官移植

Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.

Recommendations of severe acute respiratory syndrome coronavirus 2 vaccination in renal transplant recipients / 中华器官移植杂志

As novel coronavirus infection has become a major public health problem affecting human health, vaccination is the most effective means of preventing novel coronavirus infection.Therefore, besides implementing regular epidemic prevention and control, it has become the consensus of international community for effective prevention and control of novel coronavirus infection through accelerating the speed of novel coronavirus vaccination, expanding the scope of vaccination and improving public vaccination rate.Kidney transplant recipients are at an elevated risk of novel coronavirus infection.This population has been in a low immune state for a long time.Thus there are problems such as reduced immunogenicity of COVID-19 vaccine, selection and use of vaccine and breakthrough of infection.Based upon the published international and domestic data, this paper serves as a practical reference for clinicians and healthcare workers to provide consultations to kidney transplant recipients about the administration of novel coronavirus vaccine.

Clinical analysis of 81 cases of intravenous leiomyomatosis confined to pelvic cavity / 中华妇产科杂志

Objective:To investigate the clinical features, treatment and recurrence factors of intravenous leiomyomatosis (IVL) confined to the pelvic cavity after the operation.Methods:The clinical data of 81 patients who underwent surgery and were pathologically diagnosed with IVL at Women′s Hospital, School of Medicine, Zhejiang University from January 2014 to March 2021, were analyzed retrospectively to explore the influencing factors of postoperative recurrence of IVL, including age, gravidity and parity, surgical methods, intraoperative conditions and so on.Results:(1) Clinical features: the age of 81 IVL patients was (43.9±8.1) years old; increased menstrual volume in 26 cases (32%, 26/81), prolonged menstrual period in 31 cases (38%, 31/81), frequency and urgency to urinate in 4 cases (5%, 4/81), abdominal pain and abdominal distension in 8 cases (10%, 8/81), and pelvic masses in 34 cases (42%, 34/81). IVL was diagnosed right in 4 of 72 patients (6%, 4/72) underwent preoperative ultrasound, right in 11 of 51 patients (22%, 11/51) underwent magnetic resonance imaging (MRI), and right in 4 of 19 patients (4/19) underwent CT. (2) Treatment: all patients with IVL underwent surgical treatment. Surgical procedure: myomectomy in 37 cases, total hysterectomy and bilateral salpingectomy in 19 cases, total hysterectomy and bilateral salpingo-ophorectomy in 25 cases. Surgical approach: hysteroscopic operation in 6 cases, transabdominal operation in 52 cases, laparoscopic operation in 23 cases. Fifty-three cases underwent rapid intraoperative pathological examination, 17 cases (32%, 17/53) of them were diagnosed right as IVL. (3) Influencing factors of IVL postoperative recurrence: among 81 patients with IVL, 3 cases were lost to follow-up, and 8 cases (10%, 8/78) had recurrence during follow-up. Age<35 years, number of pregnancies<2, number of births<2, number of fibroids ≥10, abnormal appearance of fibroids (long, vermicular, beadlike, cystic, etc.) and IVL invasion into adjacent vessels were all the risk factors influencing postoperative recurrence of IVL (all P<0.05). Methods of operation, ovariectomy or not, IVL invasion or not, maximum diameter of IVL, abundant blood vessels near uterine fibroids were not associated with postoperative recurrence of IVL (all P>0.05). Conclusions:The clinical manifestations and preoperative auxiliary examination of IVL are lack of specificity. Doctors need to pay attention to young patients with uterine fibroids, and choose the appropriate surgical scope when the characteristic manifestations of IVL be found during the operation, or the right diagnoses of IVL in the surgery′s rapid intraoperative pathology be examined, and should remove the IVL lesions to reduce the recurrence as far as possible.

Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%‍-‍50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).

Single-center analysis of pathogenic bacteria distribution and drug resistance in renal transplantation patients during perioperative period / 中华器官移植杂志

Objective:To explore the distribution of pathogenic bacteria during perioperative period of kidney transplantation(KT)patients and examine drug resistance of major clinical pathogens to commonly used antibiotics to provide references for empirical medication of pathogenic bacteria infection after KT.Methods:From January 1, 2020 to June 30, 2021, 251 patients undergoing deceased donation KT on kidney transplant ward were selected.Clinical samples were collected and distribution and drug resistance of pathogenic bacteria examined for analyzing the incidence of possible donor-derived infections and predicting prognoses.Results:The detection rate of pathogens was 12.18%(367/3 014). A total of 225 non-repetitive strains were isolated.Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 48.89%(110/225), 43.11%(97/225)and 8.00%(18/225). The proportion of lavage fluid in all isolated bacteria was 49.78%(112/225). And Staphylococcus epidermidis and Klebsiella pneumoniae predominated.Drainage fluid accounted for 24.88%(56/225)and Pseudomonas putida and Staphylococcus haemolyticus predominated.Urine accounted for 18.67%(42/225)with a dominance of Enterococcus faecium; blood accounted for 6.22%(14/225)with a dominance of S. epidermidis.All detected pathogens showed varying degrees of resistance.The resistance rates of E. faecium to ampicillin, vancomycin and linezolid were 93.33%(28/30), 6.45%(2/31)and 38.71%(12/31). The resistance rates of K. pneumoniae and Acinetobacter baumannii to carbapenems were 71.43%(20/28)and 80.00%(12/15). The incidence of possible donor-derived infection was 3.59%(9/251)and there was no mortality.Conclusions:The detection rate of pathogenic bacteria is high in KT patients during perioperative period.There is a diverse distribution of isolates of different specimen types and all detected pathogens show varying degrees of drug resistance.Clinicians should regularly analyze the distribution characteristics and causes of drug-resistant bacteria.And antibiotics should be optimized according to the results of drug sensitivity.

Research progress of novel drug therapy for antibody-mediated rejection in kidney transplantation / 中华泌尿外科杂志

Antibody-mediated rejection (AMR) is the primary factor affecting the long-term prognosis of kidney transplant recipients and kidney allograft. Currently, there is no universally recognized or approved drug for the treatment of AMR. Therefore, more novel drug studies and clinical trials are urgently needed in order to change the long-term prognosis of kidney transplant recipients. Based on the core principles of prevention and treatment of AMR, this paper discusses the mechanism and efficacy of several new types of drugs of most concern in the treatment of AMR from three aspects: removing donor specific antibody, blocking antibody-mediated and complement-mediated tissue damage, and inhibiting the proliferation and activation of antibody-producing cells. These emerging drugs have shown potential in preventing and treating AMR and improving the prognosis of recipients, which is expected to change the dilemma of AMR treatment in the future and provide more effective treatment options for improving the long-term prognosis of kidney transplant recipients.

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

EGCG and ECG induce apoptosis and decrease autophagy via the AMPK/mTOR and PI3K/AKT/mTOR pathway in human melanoma cells / 中国天然药物

Catechins have been proven to exert antitumor effects in different kinds of cancers. However, the underlying mechanisms have not been completely clarified yet. This study aimed to assess the effects and mechanisms of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) on human melanoma skin A375 cells. Results showed that EGCG and ECG inhibited the proliferation of A375 cells and ECG showed better inhibitory effect. Flow cytometry analysis had shown that EGCG and ECG induced apoptosis and led to cell cycle arrest. EGCG and ECG decreased Bcl-2 expression and upregulated Caspase-3 protein level, indicating the development of apoptosis. Furthermore, EGCG and ECG could decreased mitochondrial membrane potential of A375 cells. In addition, the expression of Beclin-1, LC3 and Sirt3 were downregulated at protein levels, which known to be associated with autophagy. After autophagy was increased by rapamycin, the apoptotic trend was not change, indicating that apoptosis and autophagy are independent. Mechanistically, EGCG and ECG treatments decreased phosphorylated-AMPK (p-AMPK) and increased the ratios of p-PI3K, p-AKT and p-mTOR in melanoma cells. Conclusively, EGCG and ECG induced apoptosis via mitochondrial signaling pathway, downregulated autophagy through modulating the AMPK/mTOR and PI3K/AKT/mTOR signaling pathway. It indicated that EGCG and ECG may be utilized in human melanoma treatment.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial / 中西医结合学报

BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

Study on the effect and mechanism of SKA1 activated by E2F1 transcription in promoting the proliferation of liver cancer cells / 中华内分泌外科杂志

Objective:To investigate whether SKA1 is a key molecule regulating malignant proliferation of liver cancer, and further explore its mechanism to provide molecular theoretical basis for subsequent targeted therapy.Methods:The data of liver cancer from TCGA database were analyzed by bioinformatics technology. The expression of SKA1 in liver cancer was analyzed. At the same time, we also analyzed the relationship between the expression of SKA1 and the prognosis of patients with liver cancer. The hepatoma cell line overexpressing SKA1 was constructed by liposome-mediated cell transfection technique, and the effect of SKA1 on the proliferation of hepatoma cells was further tested by CCK-8 and plate cloning assay. At the same time, we found that E2F1 is also highly expressed in liver cancer, using bioinformatics technology to analyze the correlation between SKA1 and E2F1 expression, further detecting the binding site of E2F1 in the SKA1 promoter region, and using dual luciferase technology to detect E2F1 against SKA1. Transcriptional activation.Results:KA1 was highly expressed in liver cancer tissues, and the overall survival rate of liver cancer patients with high SKA1 expression was 49.8%, lower than that of patients with low SKA1 expression, showing a negative correlation. E2F1 is also highly expressed in liver cancer tissues, and the survival time of patients with liver cancer with high E2F1 expression is significantly lower than that in the low expression group, which was negatively correlated with poor prognosis. SKA1 overexpression could increase the proliferation ability of liver cancer cells by nearly 50%. SKA1 is regulated by the E2F1 transcription factor, and the E2F1 transcription factor is combined with the SKA1 promoter to transcriptionally activate the expression of SKA1 in liver cancer cells.Conclusion:E2F1 transcriptional activation of SKA1 promotes proliferation of hepatoma cells, leading to poor prognosis in patients with liver cancer

Clinical outcomes of neoadjuvant chemotherapy with Gemcitabine and Cisplatin for muscle-invasive bladder cancer / 国际外科学杂志

Objective:To investigate the clinical outcomes of neoadjuvant chemotherapy with Gemcitabine and Cisplatin (GC) for muscle-invasive bladder cancer (MIBC).Methods:Retrospective analysis of 67 MIBC patients admitted to Beijing Friendship Hospital, Capital Medical University from December 2010 to June 2020. Fifty-five MIBC patients (cT2-T4aN0M0) underwent GC plus radical cystectomy-pelvic lymph node dissection. Pathological responses, prognosis and chemotherapy toxicities were analyzed. The Chi-square test and Fisher′s exact probability method were used to compare the count data between groups. The overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier survival curve, and the Log-rank test was used to evaluate the difference between groups in the survival curve. Prognostic analysis adopts Cox proportional hazards regression model.Results:Fifty-five MIBC patients received GC plus radical cystectomy-pelvic lymph node dissection. The 81.8% patients ( n=45) received 2 cycles GC and 18.2% patients ( n=10) received 3 cycles. The complete pathological response (pT0N0M0) rate was 30.9% ( n=17) and partial response (pT 1/Tis/T aN 0M 0) rate was 10.9% ( n=6). Overall pathological response rate was 41.8%. The median follow-up was (47.0±37.7) months, 5-year OS were 82.2% and 22.1% (<pT 2 versus ≥pT 2, P<0.001), and DFS were 86.1% and 32.1% (<pT 2 versus ≥pT 2, P<0.001). Pathological response and positive lymph nodes were independent risk factors of overall survival and disease-free survival on multivariable analysis ( P<0.05). The most common chemotherapy toxicities were hematologic toxicities and gastrointestinal reactions, and none delayed surgery due to toxicities. Conclusion:Neoadjuvant GC plus radical cystectomy-pelvic lymph node dissection has a significant clinical benefit in MIBC patents and chemotherapy toxicities are well tolerated.