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 explore the application of cognitive interview (CI) in intercultural adaptation of the Happiness Scale for Middle-Aged Women (HAS-MW) .Methods:This was a qualitative study. In January 2022, 20 middle-aged women in community of Yanji City were selected by purposive sampling for two rounds of CI, and 10 subjects participated in each round of CI. According to the interview outline, we understood the understanding of the subjects on the HAS-MW items that were preliminarily localized in Chinese. The expert group discussed and revised the items of the scale according to the interview results.Results:In this study, a total of 2 rounds of cognitive interviews were conducted, the age of 10 respondents (P1-P10) in the first round was (49.00±3.55) , and the age of 10 respondents (P11-P20) in the second round was (51.00±3.16) . After the first round, 6 items in HAS-MW were revised due to "imperfect language, grammar and expression". The second round of CI results showed that the respondents understood the contents of the revised scale items and believed that they were consistent with the original scale.Conclusions:Through CI, we can comprehensively understand middle-aged women's understanding of the content of the HAS-MW, effectively find out the cognitive bias caused by improper language expression in the process of the scale's localization, improve the understanding of the content of the scale by the interviewees, which is conducive to intercultural adaptation of the HAS-MW and provides a reference for the revision of the scale.

Objective:To evaluate the inhibitory effect of a retinoid derivative ECPIRM on proliferation of a cutaneous T-cell lymphoma (CTCL) cell line HH, and to explore its potential mechanisms.Methods:Cultured HH cells were treated with ECPIRM at different concentrations of 0 (control group) , 5, 10 and 20 μmol/L separately for 72 hours, cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ECPIRM on the proliferative activity of HH cells, and flow cytometry to investigate the effect of ECPIRM on apoptosis of HH cells. Some HH cells were treated with 10 μmol/L ECPIRM for 72 hours, transcriptome sequencing was performed to investigate gene expression changes triggered by ECPIRM in HH cells, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and gene ontology (GO) enrichment analysis were then performed to analyze differentially expressed genes in HH cells induced by ECPIRM. Reverse transcription-qPCR was subsequently conducted to verify changes in key gene expression in related pathways. Intergroup differences were analyzed by using one-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:CCK8 assay showed that the 50% inhibitory concentration (IC50) of ECPIRM on HH cells was 4.91 ± 2.48 μmol/L, the viability of HH cells significantly differed among the control group, and 5-, 10-and 20-μmol/L ECPIRM groups (100.00% ± 2.87%, 49.58% ± 4.53%, 48.36% ± 2.88%, 31.44% ± 2.46%, respectively, F=162.86, P < 0.001) , and was significantly lower in the 5-, 10-and 20-μmol/L ECPIRM groups than in the control group ( t=15.36, 15.73, 20.89, respectively, all P < 0.001) . Flow cytometry showed that there was a significant difference in the apoptosis rate among the 4 groups (11.51% ± 1.84%, 23.83% ± 5.72%, 36.19% ± 8.33%, 49.75% ± 4.10%, respectively, F=17.62, P < 0.001) , and the 10-and 20-μmol/L groups showed significantly increased apoptosis rates compared with the control group ( t=4.46, 6.92 respectively, both P < 0.01) . Transcriptomics analysis revealed that the inhibitory effect of ECPIRM on the cellular proliferative activity may be related to the metabolic regulation of steroids. As reverse transcription-qPCR revealed, the 10-μmol/L ECPIRM group showed significantly decreased mRNA expression of L-amino acid oxidase (IL4I1) , acetyl-coenzyme A acetyltransferase 2 (ACAT2) , 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) , mevalonate diphosphate decarboxylase (MVD) , 3-β-hydroxysteroid-8,7-isomerase (EBP) , very low-density lipoprotein receptor (VLDLR) , 3-hydroxy 3-methylglutaryl-CoA reductase (HMGCR) compared with the control group (all P < 0.05) . Conclusion:The retinoid derivative ECPIRM exerted marked anti-proliferative and apoptosis-inducing effects on HH cells, which may be related to the decreased expression of key genes involved in steroid metabolism.

Objective:To investigate the diagnosis, treatment and prognosis of squamous cell carcinoma of renal pelvis.Methods:The clinic data of 28 cases with squamous cell carcinoma of renal pelvis confirmed by pathologic examination treated during June 2007 and September 2019 was retrospectively analyzed. There were 19 male and 9 female patients, with a median age of 56 years. Hematuria was present in 18 cases, flank pain was present in 11 cases, and abdominal mass was present in 1 case. All 28 cases accepted CT or MRI examination. Renal pelvis or renal tumors were found in 26 cases, and severe hydronephrosis was observed in 2 cases. 2 cases underwent PET/CT, and bone metastasis was found in 1 case. Preoperative diagnoses were renal pelvic tumor in 13 cases, renal tumor in 13 cases and renal abscess in 2 cases. Coexisting renal calculi or renal pelvic calculus was detected in 19 cases. All 28 cases underwent surgical excision, including radical nephroureterectomy in 13 cases, radical nephrectomy in 12 cases, palliative resection in 1 case, and pyonephrenectomy in 2 cases. Enlarged lymph nodes were found in 9 cases during the surgery, and local lymph node dissection was performed in these cases.Results:The mean diameter of the tumors was 8.5 cm. Histopathological examination revealed that 9 cases were well differentiated, 11 cases were moderately differentiated, and 8 case was poorly differentiated. 1 case had pT 2 stage, 15 cases had pT 3 stage and 12 cases had pT 4 stage. 9 cases had lymph node metastasis. 5 cases had renal vein thrombosis. Immunohistochemistry staining exhibited consistent characteristics including CK5(+ ), 34βE12(+ ), p63(+ ), CK20(-) and GATA3(-). Postoperatively, 12 cases received adjuvant therapy including chemotherapy, radiotherapy and/or immunotherapy. Within a median follow-up of 6.0 months (ranging 1-80 months), median overall survival was 10.0 months. 15 cases died of tumor progression. Conclusion:Squamous cell carcinoma is a rare and highly aggressive neoplasm, typically associated with long-lasting renal calculi, hydronephrosis and chronic inflammation. The diagnosis should be established on pathologic examination.CK5, 34βE12 and p63 positivity contribute to the diagnosis of squamous cell carcinoma. Surgery is the foremost choice of treatment, but the risk of recurrence and metastasis is high. The prognosis is extremely poor as the majority of patients are diagnosed with advanced stages.

Objective:To study the pathological characteristics, diagnosis and treatment of primary adenocarcinoma of renal pelvis and ureter.Methods:The clinical pathological characteristics, treatment and prognosis of 5 patients with adenocarcinoma of upper urinary tract treated between January 2007 and May 2019 was retrospectively reviewed. There were 4 male and 1 female patients, with a median age of 60 years. The major symptoms were hematuria in 5 cases and low back pain in 4 cases. All cases underwent B-ultrasound and CT examination, and 4 cases accepted cystoscopy. Preoperative diagnoses were ureter tumor in 2 cases, renal pelvis tumor in 1 case, renal tumor in 1 case and renal calculus in 1 case.Results:5 cases were treated with surgery. Radical nephroureterectomy was performed in 3 cases, and nephrectomy in one case. 1 case underwent first-stage percutaneous nephrolithotomy and second-stage radical nephroureterectomy due to the discovery of tumor. 1 case was treated with radiotherapy and immune checkpoint inhibitor postoperatively. The mean diameter of the tumors was 4.4 cm. There were 3 renal pelvis adenocarcinomas and 2 ureter adenocarcinomas confirmed by pathologic examination, including 3 cases of pT 3 stage and 1 case of pT 4 stage. Lymph node metastasis was found in 2 cases. Immunohistochemistry revealed that CDX2(+ ), p63(-), GATA3(-), β-catenin(-)were the common features of five cases. The median survival was 12 months with a median follow-up of 6 months. 2 cases died of tumor progression within 1 year. Conclusions:Adenocarcinoma is an extremely rare malignancy, typically associated with long-standing calculi and chronic inflammation. Given the fact that clinical and imaging findings are nonspecific, the diagnosis is based on pathologic examination, supported by glandular structure of histology. Immunohistochemical staining exhibited CDX2 and CK20 positivity and β-catenin negativity, moreover, GATA3, p63 and CK7 was usually negative or partially positive. Surgery is the foremost choice of treatment. The prognosis is correlated with subtypes, whereas the overall prognosis is poor due to high rates of recurrence and metastasis.

Objective To determine the influence of abiraterone acetate (AA) on neuroendocrine differentiation (NED) in metastatic castration-resistant prostate cancer (mCRPC) and the prognostic predicting value of the serum NED markers in mCRPC patients treated with AA.Methods We conducted an analysis in 115 chemotherapy-naive mCRPC patients who were treated with chemotherapy in Renji hospital from 2013 to 2017.The median age was 70,ranged from 65 to 76 years old.The median CgA,NSE and PSA levels were 101.1 ng/ml (78.5-150.0 ng/ml),13.4 ng/ml (10.5-17.6 ng/ml) and 38.8 ng/ml (11.2-123.2 ng/ml),respectively.Among them,48 cases were classified as the group without AA treatment.The other 67 cases were classified as group after AA failure.In group without AA treatment,the median CgA,NSE and PSA levels were 109.1 ng/ml(80-151.5 ng/ml);13.8 ng/ml(10.8-18.2 ng/ml) and 39.2 ng/ml (8.6-200 ng/ml),respectively.In group after AA failure,the median CgA,NSE and PSA levels were 105.4 ng/ml(78.8-175.5 ng/ml),13.8 ng/ml(10.8-17.6 ng/ml) and 39.0 ng/ml(8.4-219.8 ng/ml),respectively.In the group with serial evaluation of NED markers during AA treatment,the median serum CgA,NSE levels at baseline were 115.9 ng/ml(90.1-201.5 ng/ml),13.3 ng/ml (10.4-18.1 ng/ml),respectively.The endpoints were PSA PFS(progression-free survival) and radiographic PFS (rPFS).Results In 34 patients with serial evaluation,serum NED markers level in 19 patients increased after the failure of AA treatment.Median serum CgA and NSE levels were 115.9 ng/ml(90.1-201.5 ng/ml)and 13.25 ng/ml (10.37-18.14 ng/ml) at baseline.Median serum CgA and NSE levels were 129.6ng/ml (75.5-230.5 ng/ml) and 14.7 ng/ml (11.8-19.1 ng/ml) after 6 months treatment,respectively.The median serum CgA and NSE levels were 130.4 ng/ml (95.7-205.7 ng/ml) and 15.2 ng/ml(12.4-18.7 ng/ml) at the time of failure of AA treatment,respectively.There was no significant difference of NED markers between baseline and failure of AA treatment (P =0.243).In logistic univariate analysis,AA treatment and its duration were not independent factors influencing NED(P =0.30;P =0.52).Compared with the NED markers elevation group in the first 6 months of AA treatment and baseline supranormal NED markers group,the NED markers decline group(PSA PFS(17.1 vs.10.4 months,P ＜ 0.001) and rPFS (17.0 vs.10.4 months,P =0.003)) and baseline normal NED markers group(PSA PFS(14.1 vs.9.5 months,P =0.001) and rPFS(16.4 vs.10.5 months,P ＜ 0.001)) has a longer median PSA PFS and rPFS respectively.In multivariate Cox analysis,baseline NED markers level and NED markers variation during the first 6 months of AA treatment remained significant predictors of rPFS(P ＜ 0.05),and PSA-PFS (P ＜ 0.05).Conclusions We found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment,and AA might not significantly lead to progression of NED of mCRPC in general.Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.Serum NED markers elevation during the first 6 months of AA treatment and elevated baseline NED markers levels indicated poor prognosis in mCRPC treated with AA.

Objective To summarize the experiences of postoperative care of 7 patients with lung transplantation patients receiving high flow nasal cannulae oxygen therapy. Methods The key points to ensure the success of operation were oxygen therapy waiting for lung transplantation,sequential treatment after tracheal intubation, assisted by fiberoptic bronchoscopy, nasal high flow oxygen therapy failed to switch to non-invasive treatment or re intubation. Results All 7 patients got through the intensive care period successful. Conclusions High flow nasal cannulae can improve the comfort and compliance of lung transplant patients,and easy to operate.

This paper summarized nursing care in intra-hospital transfer of 13 critically ill patients with extracorporeal membrane oxygenation. The key points to guarantee safety of critically ill patients were establishing a well-trained professional team and developing standardized procedures,and applying checklist for ECMO Transfer. The key points in nursing were assessment and pretreatment,homogenized nursing during transfer and effective handover after transfer. As a result,six cases of avian influenza patients successfully completed CT ex-amination,five cases of lung re-transplant patients and two cases of lung transplant patients were successfully trans-ferred to the operating room.

Objective To study the expression of vesicular GABA transporter and vesicular glutamate transporter 1 in de‐pression .Methods Mice was divided into control group and defeat group stochastically .By social defeat model and social avoidance , the defeat group was divided into two groups:susceptible group and unsusceptible group .Synaptic proteins were extracted respec‐tively from the 3 groups .We detected the expression abundance of VGAT and VGLUT1 by Western blot .Results Compared with the control group ,in susceptible group ,the residence time in the contact area was significantly reduced ,and the residence time in the corner area was significantly increased ,with statistical difference(P<0 .05) .In the prefrontal cortex and hippocampus ,Com‐pared with the control group and the unsusceptible group ,the expression levels of VGLUT1 and VGAT were increased in the sus‐ceptible group(P<0 .05) .there were no statistically significant in VGLUT1 and VGAT leveles between control group and the un‐susceptible group(P>0 .05) .In the striatum ,although the expression levels of VGAT and VGLUT1 were increased in susceptible group ,but in unsusceptible group ,the expression of these proteins also increased significantly .Conclusion The prefrontal cortex and hippo‐campus excitability and inhibitory vesicle transport were changed in depression ,which may relate to the transcription disorder .

Objection To observe the change rules of quantity and species of diatom sin Hunhe River in Shenyang and to provide technology and scientific evidence for drow ning identification and the location of drow ning in forensic investigation. Methods In 2011, different locations for collecting water sam pleswere chosen in Hunhe River in Shenyang. Water sam pleswere collected and variation of quantity and species of diatom swere observed every month. And variation of dom inant species of diatom swas ob-served every week. Results The quantity, speciesand dom inant species of diatom sin Hunhe River in Shenyang varied with different tim eand locations. The quantity and species of diatom swere lowest from Decem ber to February and gradually increased, reaching peak in May and second peak in October, and then gradually decreased. The dom inant species of diatom s varied significantly adjacent two weeksat same location from April to N ovem ber, but had little changesat different locationsin same week from July to August. Conclusion The change rules of quantity and species of diatom sare com plicated and affected by various factors such as environm ent and hydrology. The change rules of speciesand quantity of diatom s should be considered in forensic investigation of drow ning identification and the lo-cation of drow ning.