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

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.

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.

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

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.

Objective To summarize the clinicopathological characteristic,diagnosis and treatment of iatrogenic biliary tree destruction.Methods The retrospective cross-sectional study was conducted.The clinical data of 11 patients with iatrogenic biliary tree destruction who were admitted to the Chinese PLA General Hospital (9 patients) between January 1990 and December 2013 and Beijing Tsinghua Changgung Hospital (2 patients) between December 2014 and May 2017 were collected.Observation indicators:(1) causes and parts of destruction;(2) clinical manifestation;(3) imaging performance;(4) treatment;(5) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect long-term prognosis of patients up to April 2018.Measurement data with skewed distribution were described as M (range).Results (1) Causes and parts of iatrogenic biliary tree destruction:causes of iatrogenic biliary tree destruction in 11 patients:transcatheter arterial embolization for hepatic hemangioma was performed in 7 patients,high intensity focused ultrasound for hepatic hemangioma in 1 patient,arterial embolization for false aneurysm in 1 patient,sclerosant injection for hepatic echinococcosis in 1 patient,and cyberknife radiotherapy for hepatocellular carcinoma in 1 patient.Parts of biliary tree destruction of 11 patients:5,3,2 and 1 respectively involved bilateral biliary tree,right biliary tree,bilateral main biliary ducts in hepatic port and left biliary tree.(2) Clinical manifestation:11 patients had symptoms of recurrent chills and fever,and combined with different degrees of jaundice.The initial symptom occurred in 2 weeks to 3 months after iatrogenic biliary tree destruction.Of 11 patients,7 were complicated by different degrees of hepatic abscess,and abscess involving left and right half liver were detected in 4 patients,aggregating in right half liver in 2 patients and aggregating in left half liver in 1 patient.Eight patients had secondary biliary cirrhosis,portal hypertension,splenomegaly and hypersplenism during the late course of disease.(3) Imaging performance:magnetic resonanced cholangio-pancreatography (MRCP) and cholangiography examinations showed missing bile duct in necrosis area,beading-like stricture and dilation of damaged biliary tree,reducing proximal bile duct branches and associated gallbladder necrosis.CT and MRI examinations showed that structure of distribution area of damaged biliary tree disappeared or bile duct wall was thickened,and hepatic abscesses of patients were scattered and multiple.Five patients had significantly secondary liver atrophy-hypertrophic syndrome,showing atrophy of right liver and hyperplasia of left liver.Radiotherapy-induced biliary tree destruction showed a characteristic of continued progress,localized abnormality in the early stage and typical imaging changes after the damage stability in the late stage.(4) Treatment:of 11 patients,4 didn't undergo surgery,and 7 underwent 18 intentional and conclusive surgeries (1-4 times / per case).(5) Follow-up:11 patients were followed up for 2-132 months,with a median time of 73 months.During the follow-up,2,1 and 8 patients had respectively excellent,good and poor prognoses.Among 11 patients,4 died (2 died of severe infection and 2 died of biliary cirrhosis),and 7 survived.Conclusions Iatrogenic biliary tree destruction is easy to cause hepatic abscess,liver atrophy-hypertrophic syndrome or biliary cirrhosis,and it can be diagnosed by imaging examination.The definitive treatment should be followed by liver resection or liver transplantation of involving area according to the extent of damage.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

The 8th Japan-China Hepato-Pancreato-Biliary Symposium was held in Tokyo,Japan from 22nd to 23rd November 2018.The meeting was convened coincidently with the 80th Annual Congress of Japanese Surgical Association,which attracted the participation of Chinese and Japanese hepatobiliary and pancreatic surgeons.The symposium aimed to explore the latest achievements and clinical issues of diagnosis and treatment for hepato-pancreato-biliary diseases.In this article,authors reviewed the up-to-date research information in order to share the experience,achievements and new information in the field of hepatobiliary and pancreatic diseases with colleagues.

Objective To analyze the clinical features and definitive repair strategies of bile duct strictures after hepatectomy.Methods The clinical data of patients undergoing definite repair for bile duct strictures after hepatectomy in the PLA General Hospital from 2000 to 2014 and Beijing Tsinghua Changgung Hospital from 2014 to 2017 were retrospectively collected.Results Twenty-one patients with bile duct stricture after hepatectomy were treated with reoperation.Among them,13 cases showed continuous bile leakage after operation.The types of hepatectomy include 10 cases of left or extended left hemihepatectomy,7 cases of right or extended right hemihepatectomy,2 cases of mesohepatectomy,and 2 cases of hepatic caudate labectomy.According to classification formulated by the Biliary Surgery Group of Chinese Medical Association,the types of injuries of the patients included four of Ⅱ 2,twelve of Ⅱ 3,and five of Ⅱ 4 respectively.19 of 21 patients underwent definitive repair with hepaticojejunostomy.The long-term follow-up success rate was 89.0％.Conclusions Biliary injury after hepatectomy in which the injury affects the secondary or below hepatic ducts requires surgical repair.Hepaticjejunostomy is an effective definitive repair method.Hepaticjejunostomy for bile duct stenosis after right hemihepatectomy always need to dissect the left intrahepatic bile duct by a hilar plate approach or UPV approach,due to the effect of hepatic portal transposition.Surgical repair for bile duct stenosis after the left hepatectomy,always need the incision of the right anterior and right posterior hepatic duct,due to extensive injuries of hepatic duct.