Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe dose-limiting adverse event of chemotherapy. Presently, the mechanism underlying the induction of CIPN remains unclear, and no effective treatment is available. In this study, through metabolomics analyses, we found that nab-paclitaxel therapy markedly increased serum serotonin [5-hydroxtryptamine (5-HT)] levels in both cancer patients and mice compared to the respective controls. Furthermore, nab-paclitaxel-treated enterochromaffin (EC) cells showed increased 5-HT synthesis, and serotonin-treated Schwann cells showed damage, as indicated by the activation of CREB3L3/MMP3/FAS signaling. Venlafaxine, an inhibitor of serotonin and norepinephrine reuptake, was found to protect against nerve injury by suppressing the activation of CREB3L3/MMP3/FAS signaling in Schwann cells. Remarkably, venlafaxine was found to significantly alleviate nab-paclitaxel-induced CIPN in patients without affecting the clinical efficacy of chemotherapy. In summary, our study reveals that EC cell-derived 5-HT plays a critical role in nab-paclitaxel-related neurotoxic lesions, and venlafaxine co-administration represents a novel approach to treating chronic cumulative neurotoxicity commonly reported in nab-paclitaxel-based chemotherapy.
Paclitaxel/toxicity* ; Animals ; Albumins/adverse effects* ; Serotonin/metabolism* ; Mice ; Humans ; Male ; Female ; Venlafaxine Hydrochloride/therapeutic use* ; Neurotoxicity Syndromes/metabolism* ; Middle Aged ; Schwann Cells/metabolism* ; Peripheral Nervous System Diseases/drug therapy* ; Antineoplastic Agents

OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester-ase 1(CES1)and CES2 was detected to investigate the herb-drug interactions(HDIs)of TWHF.METHODS Human liver microsomes catalysed hydrolysis of 2-(2-benzoyl-3-methoxyphenyl)benzothi-azole(BMBT)and fluorescein diacetate(FD)were used as the probe reaction to phenotype the activity of CES1 and CES2,respectively.The residual activities of CES1 and CES2 were detected by ultra-high performance liquid chromatography(UPLC)after intervention with celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine(100 μmol·L-1).Kinetics analysis,involving half inhibitory concentra-tion(IC50),inhibition type and kinetic parameter(Ki),and in vitro-in vivo extrapolation(IVIVE),was carried out to predict the HDIs between these compounds and CES-metabolizing drugs.Molecular docking was performed to analyze the ligand-enzyme interaction.RESULTS Out of the six main con-stituents of TWHF,only celastrol exhibited strong inhibition towards both CES1 and CES2,with the inhibitory rates of 97.45%(P<0.05)and 95.62%(P<0.05),respectively.The IC50 was 9.95 and 4.02 mol·L-1,respectively,and the types of inhibition were all non-competitive inhibition.Based on the kinetics analysis,the Ki values were calculated to be 5.10 and 10.55 μmol·L-1 for the inhibition of celastrol on CES1 and CES2,respectively.IVIVE indicated that celastrol might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CES1.Molecular docking results showed that hydrogen bonds and hydrophobic contacts contributed to the interaction of celastrol and CESs.CONCLUSION The inhibitory effect of celastrol on CES1 and CES2 might cause HDIs with clinical drugs hydrolysed by CESs.

The ultrasonic manifestations of benign and malignant breast imaging-reporting and data system(BI-RADS)4 lesions overlap in some degrees,is able to result in unnecessary biopsy or untimely therapy.Accurate classifying the nature of BI-RADS 4 breast lesions can provide reliable references for clinical decision-making.The progresses of application of new ultrasonic technologies,including automated breast volume scanner,superb micro-vascular imaging,elastography,contrast-enhanced ultrasound and artificial intelligence for assisting diagnosis of BI-RADS 4 lesions were reviewed in this article.

Surgery is the main treatment for patients with hepatocellular carcinoma to achieve long-term survival. However, only 20%-30% of patients can receive radical surgery. How to optimize the surgery oriented comprehensive treatment strategy and enable patients to successfully downstage to surgery are key issues to be solved in hepatocellular carcinoma treatment in China. Selective internal radiation therapy with yttrium-90 microspheres ( 90Y-SIRT) has strong ability of tumor killing, and it is reported that 90Y-SIRT is an ideal downstaging and bridging therapy for hepatocellular carcinoma, due to its superior downstaging efficacy compared with transarterial chemoembolization. Based on the introduction of characteristics of 90Y-SIRT, the authors review the clinical research progress of 90Y-SIRT in the preoperative downstaging and bridging treatment of hepatocellular carcinoma before liver transplantation, and discuss 90Y-SIRT-based conversion strategy. The 90Y-SIRT has shown syner-gistic effect with targeted therapy and immunotherapy, and will have a broad application prospect in downstaging and conversion therapy in the future.

Surgery is the main treatment for patients with hepatocellular carcinoma to achieve long-term survival. However, only 20%-30% of patients can receive radical surgery. How to optimize the surgery oriented comprehensive treatment strategy and enable patients to successfully downstage to surgery are key issues to be solved in hepatocellular carcinoma treatment in China. Selective internal radiation therapy with yttrium-90 microspheres ( 90Y-SIRT) has strong ability of tumor killing, and it is reported that 90Y-SIRT is an ideal downstaging and bridging therapy for hepatocellular carcinoma, due to its superior downstaging efficacy compared with transarterial chemoembolization. Based on the introduction of characteristics of 90Y-SIRT, the authors review the clinical research progress of 90Y-SIRT in the preoperative downstaging and bridging treatment of hepatocellular carcinoma before liver transplantation, and discuss 90Y-SIRT-based conversion strategy. The 90Y-SIRT has shown syner-gistic effect with targeted therapy and immunotherapy, and will have a broad application prospect in downstaging and conversion therapy in the future.

OBJECTIVE: To evaluate the effectiveness of robot-guided percutaneous fixation and decompression via small incision in treatment of advanced thoracolumbar metastases. METHODS: A clinical data of 57 patients with advanced thoracolumbar metastases admitted between June 2017 and January 2021 and met the selection criteria was retrospectively analyzed. Among them, 26 cases were treated with robot-guided percutaneous fixation and decompression via small incision (robot-guided group) and 31 cases with traditional open surgery (traditional group). There was no significant difference in gender, age, body mass index, lesion segment, primary tumor site, and preoperative Tokuhashi score, Tomita score, Spinal Instability Neoplastic Score (SINS), visual analogue scale (VAS) score, Oswestry disability index (ODI), Karnofsky score, and Frankel grading between groups ( P>0.05). The operation time, hospital stays, hospital expenses, intraoperative blood loss, postoperative drainage volume, duration of intensive care unit (ICU) stay, blood transfusion, complications, and survival time were compared. The pedicle screw placement accuracy was evaluated according to the Gertzbein-Robbins grading by CT within 4 days after operation. The pain, function, and quality of life were evaluated by VAS score, ODI, Karnofsky score, and Frankel grading. RESULTS: During operation, 257 and 316 screws were implanted in the robot-guided group and the traditional group, respectively; and there was no significant difference in pedicle screw placement accuracy between groups ( P>0.05). Compared with the traditional group, the operation time, hospital stays, duration of ICU stay were significantly shorter, and intraoperative blood loss and postoperative drainage volume were significantly lesser in the robot-guided group ( P<0.05). There was no significant difference in hospital expenses, blood transfusion rate, and complications between groups ( P>0.05). All patients were followed up 8-32 months (mean, 14 months). There was no significant difference in VAS scores between groups at 7 days after operation ( P>0.05), but the robot-guided group was superior to the traditional group at 1 and 3 months after operation ( P<0.05). The postoperative ODI change was significantly better in the robot-guided group than in the traditional group ( P<0.05), and there was no significant difference in the postoperative Karnofsky score change and Frankel grading change when compared to the traditional group ( P>0.05). Median overall survival time was 13 months [95% CI (10.858, 15.142) months] in the robot-guided group and 15 months [95% CI (13.349, 16.651) months] in the traditional group, with no significant difference between groups ( χ ²=0.561, P=0.454) . CONCLUSION Compared with traditional open surgery, the robot-guided percutaneous fixation and decompression via small incision can reduce operation time, hospital stays, intraoperative blood loss, blood transfusion, and complications in treatment of advanced thoracolumbar metastases.
Humans ; Blood Loss, Surgical ; Quality of Life ; Retrospective Studies ; Robotics ; Surgical Wound ; Decompression

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. It is highly contagious and can cause death in severe cases. As reported by the World Health Organization (WHO), as of 6:36 pm Central European Summer Time (CEST), 12 August 2022, there had been 585 950 285 confirmed cases of COVID-19, including 6 425 422 deaths (WHO, 2022).
Humans ; COVID-19 ; SARS-CoV-2 ; Mental Health ; Cohort Studies ; Quality of Life ; China/epidemiology* ; Health Personnel ; Hospitals ; Lung

This manuscript is a narrative review on experience in the healthcare public-private partnerships (PPP) field project in China. The PPP model allows healthcare officials to share the risk of building new facilities with the private sector. The objective of this study is to evaluate and to review the PPP of healthcare sector in China, and to investigate the critical success factors and best practice of PPP. We adapted the PPP evaluation framework of the World Bank Independent Evaluation Group as our conceptual framework to summarize the literatures. The current study systematically reviewed the evolution and current status of public and private hospitals development in China, and to investigate factors related to the successful and less successful deployment and performance of PPP in the healthcare sector of China, and to develop best practice models of PPP among hospitals of China. We found that the PPP organizations providing finance and political risk coverage, thus enabling specific PPP transactions to reach financial closure—potentially setting demonstration effects. Such PPPs may then contribute to improving access to infrastructure and social services, which drives economic growth and other optimal outcomes.

This manuscript is a narrative review on experience in the healthcare public-private partnerships (PPP) field project in China. The PPP model allows healthcare officials to share the risk of building new facilities with the private sector. The objective of this study is to evaluate and to review the PPP of healthcare sector in China, and to investigate the critical success factors and best practice of PPP. We adapted the PPP evaluation framework of the World Bank Independent Evaluation Group as our conceptual framework to summarize the literatures. The current study systematically reviewed the evolution and current status of public and private hospitals development in China, and to investigate factors related to the successful and less successful deployment and performance of PPP in the healthcare sector of China, and to develop best practice models of PPP among hospitals of China. We found that the PPP organizations providing finance and political risk coverage, thus enabling specific PPP transactions to reach financial closure—potentially setting demonstration effects. Such PPPs may then contribute to improving access to infrastructure and social services, which drives economic growth and other optimal outcomes.

It is known that LINC01018 and CDK6 are associated with the occurrence, progression and recurrence of malignant tumor. Our preliminary data showed that the expression of LINC01018 was down-regulated and that of CDK6 was up-regulated, which were related with the malignancy grade. Bioinformatics suggested that E2F1 binding site exist in the CDK6 promoter region, and LINC01018 might interact with E2F1. Thus we speculate that the expression of LINC01018 in malignant tumor is decreased. The interaction between LINC01018 and E2F1 activates E2F1, promotes the transcription activation of CDK6, and affects tumor proliferation, invasion and metastasis. All these are expected to reveal the effect and mechanisms of LINC01018 in the development and regulation of malignant tumor, and provide new ideas and evidences for its treatment.