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: 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

Objective:To explore the risk factors affecting the incidence of acute kidney injury(AKI)after liver transplantation(LT).Methods:From November 2019 to November 2022, clinical data were retrospectively reviewed for 105 recipients of classic orthotopic LT.There are 89 males and 16 females with an age range of(50.52±10.35)years.They are assigned into two groups of AKI(66 cases)and non-AKI(39 cases)according to the AKI diagnostic and staging criteria of Global Kidney Disease Prognosis Organization in 2012.General profiles and clinical data(e.g.previous medical history, MELD score, total bilirubin, albumin, serum creatinine level, coagulation function, anhepatic phase and time to surgery)of two groups of recipients are compared.The factors with statistically significant differences are included into multivariate Logistic regression analysis for obtaining independent risk factors for early AKI post-LT.Results:Among them, 66 patients developed AKI within 7 days post-operation with an incidence rate of 62.86%(66/105).The clinical stages of AKI are Ⅰ(46 cases, 69.70%), Ⅱ(10 cases, 15.15%)and Ⅲ(10 cases, 15.15%).Statistically significant inter-group differences exists in age, abdominal surgery history, preoperative serum level of creatinine, operative duration, anhepatic phase and intraoperative plasma transfusion(all P<0.05).Multivariate Logistic regression analysis indicated that abdominal surgery history( OR=5.803, 95% CI: 1.008~33.401, P=0.049), anhepatic phase( OR=1.054, 95% CI: 1.008~1.101, P=0.020)and preoperative serum level of creatinine( OR=0.968, 95% CI: 0.943~0.994, P=0.016)are independent risk factors for early AKI after classical orthotopic LT recipients. Conclusions:Abdominal surgery history, anhepatic phase, and preoperative serum level of creatinine are independent risk factors for early AKI in classic orthotopic LT recipients.

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.

Under the diagnosis-related groups(DRG) prospective payment system, innovative health technologies with high costs and risks may be limited to some extent. How to balance the increase of health care cost and the development of innovative health technology is a difficult problem to be solved in the current reform. By studying the relatively mature payment systems of innovative health technologies in the world, the authors found that countries generally adopted additional payment or compensation to encourage the development of new technologies. But at the same time, a relatively perfect health technology assessment and payment management mechanism had been established to ensure the standardized operation of payment plan. These international advanced experience and practice could provide references for China′s innovative health technology payment strategy under the DRG payment system. It is suggested to establish a scientific and reasonable assessment mechanism of innovative health technology, create a special access channel for innovative health technology with limited short-term evidence, and gradually form a long-term incentive mechanism of innovative health technology in DRG payment system.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

Objective:Since December 2019, novel coronavirus infection has occurred in Hubei province and spread throughout the country quickly. This new crown viral pneumonia was named as coronavirus disease of 2019 (COVID-19) by WHO. However, at present, there is a high incidence of acute aortic dissection in winter and spring. How to prevent the spread of the epidemic and choose the appropriate treatment is an important topic for the patients with acute aortic dissection.Methods:From January 16, 2020 to February 26, 2020, a total of 37 of acute aortic dissection operations were carried out in several cardiovascular surgery centers in Hubei Province. There were 18 cases of Stanford type A aortic dissection and 19 cases of Stanford type B aortic dissection. There were 10 cases (55.55%) with ascending aorta replacement and 7 cases (38.89%) with Bentall procedure for aortic root surgery, and total arch replacement with stented elephant trunk implantation were performed in 14 cases (77.8%). In 19 patients with Stanford type B aortic dissection, thoracic endovascular aortic repair was performed, with the left subclavian artery chimney technique in 2 cases.Results:No deaths occurred within 30 days of hospitalization. Preoperative nucleic acid testing excluded 7 cases of novel coronavirus infection, and 3 suspected cases underwent emergency surgery. the three-level protective standard was adopted in the majority of the surgeries(62.2%, 23/37), and 11 patients were negative in the reexamination of viral nucleic acid after the operation.Conclusion:During the epidemic period, patients with acute aortic dissection should be carefully identified with actife COVID-19 before surgery. The treatment principles-" prevention and control of pneumonia epidemic should be emphasized, conservative medical management should be taken in the comfirmed cases, the selective operation should be delayed as far as possible, and the operation should be reasonable performed in critical cases" should be followed, which can save patients' lives to the greatest extent and prevent the spread of the virus.

Objective: To investigate the clinical application value of single nucleotide polymorphism (SNP) haplotype analysis in the preimplantation genetic diagnosis (PGD) of monogenic diseases. Methods: The whole genome amplification products of biopsied trophectoderm cells were analyzed by SNP haplotype analysis and verified by Sanger sequencing. Results: A total of 205 embryos were performed SNP haplotype analysis and Sanger sequencing. Among them, Sanger sequencing failed in 14.63% (30/205) of embryos, and SNP haplotype analysis failed in 0.98% (2/205) of embryos. The failure rate of the latter was significantly lower than that of the former (P＜0.05). There were consistent results in 155 (75.61%) embryos, and inconsistent results in 18 (8.78%) embryos. Forty-five embryos in 41 cycles were performed embryo transplantation. The clinical pregnancy rate was 70.73% (29/41) and the implantation rate was 71.11% (32/45). The results of prenatal diagnosis of amniotic fluid during the second trimester of pregnancy were completely consistent with those of SNP haplotype analysis. Conclusion SNP haplotype analysis is accurate, and its failure rate is lower than that of Sanger sequencing. It can be effectively used in the PGD of clinical monogenic diseases.

Objective To explore the relationship between cytotoxin associated protein A (cagA), cytotoxin associated protein E(cage), vacuolating cytotoxin A (vacA) genotypes of Helicobacter pylori (Hp) and the upper digestive tract diseases. Methods A total of 112 patients with upper gastrointestinal diseases were selected. The cagA, cagE, vacA genotypes of Hp strains in gastric mucosa of the patients were detected and analyzed. Results All Hp strains in the gastric mucosa samples of patients were found with both cagA gene and cagE gene expression, and the positive rate was 100%. The positive rates of vacA s1/m2 genotype in the patients were the highest with 54.1% and 60.5% respectively, followed by the vacA s1/mlb genotype and vacA s1/m- phenotypes, and the positive rates were from 13.2% to 21.1%. The differences of positive rates of each genotypes in Hp genes between the patients with peptic ulcer and chronic gastritis were not significant (P>0.05). Conclusion Hp strains in gastric mucosa patients with upper gastrointestinal diseases show the advantage expressions of cagA, cagE, vacA s1/m2 subtypes, which refers that such virulence phenotypes may play important roles in initiation and promotion process of upper gastrointestinal diseases by Hp, but the correlation with the type of upper digestive tract diseases is not proved.

Objective To explore the relationship between cytotoxin associated protein A (cagA), cytotoxin associated protein E(cage), vacuolating cytotoxin A (vacA) genotypes of Helicobacter pylori (Hp) and the upper digestive tract diseases. Methods A total of 112 patients with upper gastrointestinal diseases were selected. The cagA, cagE, vacA genotypes of Hp strains in gastric mucosa of the patients were detected and analyzed. Results All Hp strains in the gastric mucosa samples of patients were found with both cagA gene and cagE gene expression, and the positive rate was 100%. The positive rates of vacA s1/m2 genotype in the patients were the highest with 54.1% and 60.5% respectively, followed by the vacA s1/mlb genotype and vacA s1/m- phenotypes, and the positive rates were from 13.2% to 21.1%. The differences of positive rates of each genotypes in Hp genes between the patients with peptic ulcer and chronic gastritis were not significant (P>0.05). Conclusion Hp strains in gastric mucosa patients with upper gastrointestinal diseases show the advantage expressions of cagA, cagE, vacA s1/m2 subtypes, which refers that such virulence phenotypes may play important roles in initiation and promotion process of upper gastrointestinal diseases by Hp, but the correlation with the type of upper digestive tract diseases is not proved.