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 value of dual-phase enhanced CT radiomics in predicting post-acute pancreatitis diabetes mellitus(PPDM-A).Methods A total of 145 patients with acute pancreatitis(AP)were retrospectively collected,including 62 patients in PPDM-A group and 83 patients in non-PPDM-A group.The patients were randomly divided into training set and test set at a ratio of 7︰3,the pancreatic parenchyma in arterial phase and venous phase was delineated and the radiomics features were extracted.Vari-ance threshold method,univariate selection method and least absolute shrinkage and selection operator(LASSO)were used to screen radiomics features.The prediction performance of the model was evaluated by the area under the curve(AUC).The DeLong test was used to compare the prediction efficiency between the models,and the calibration curve and decision curve were used to evaluate the prediction efficiency of the model.Results The AUC of arterial phase model,venous phase model,combined arterial venous phase model,clinical model and radiomics combined clinical model in the training set were 0.845,0.792,0.829,0.656 and 0.862,respec-tively.The DeLong test results showed that only the difference between the radiomics combined clinical model and the clinical model in the training set and the test set was statistically significant(P<0.05).The decision curve showed that the radiomics combined clinical model had high clinical practicability in a certain range,and the calibration curve showed that the radiomics combined clinical model had the best fitting degree with the actual observation value.Conclusion Based on the dual-phase enhanced CT radiomics combined clinical model,PPDM-A can be predicted more accurately,and it can provide a certain reference value for the clinical development of per-sonalized treatment programs.

Objective·To evaluate the relationship between anxiety level,alexithymia degree and quality of life in patients with anxiety disorders.Methods·Anxiety disorder patients admitted to the outpatient department of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine from October 1,2020 to March 31,2023 were selected as the research subjects,and 438 patients were ultimately included after exclusion.Among them,there were 271 patients with generalized anxiety disorder,101 patients with panic disorder,48 patients with social anxiety disorder,12 patients with agoraphobia,and 6 patients with specific phobia.Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale-17(HAMD-17),the twenty-item Toronto Alexithymia Scale(TAS-20)and World Health Organization Quality of Life Scale-Brief Form Questionnaire(WHOQOL-BREF)were used to assess the patients'anxiety level,depression level,alexithymia degree and quality of life,respectively,and the scale scores of patients with different subtypes of anxiety disorders were evaluated.Spearman correlation coefficient was used to analyze the correlation between anxiety level,depression level,alexithymia degree and quality of life in patients with anxiety disorders.Stepwise regression model was used to analyze the key variables affecting the quality of life in patients with anxiety disorders.Results·There were no significant differences in HAMA score,HAMD-17 score and TAS-20 score among patients with different subtypes of anxiety disorders,but the differences in WHOQOL-BRIEF score were statistically significant(H=10.076,P=0.039).The results of Spearman correlation analysis showed that the WHOQOL-BRIEF score of anxiety disorder patients was negatively correlated with HAMA score,HAMD-17 score and TAS-20 score(r=-0.256,P=0.000;r=-0.311,P=0.000;r=-0.342,P=0.000).The results of stepwise regression analysis showed that age,HAMA score,HAMD-17 score and TAS-20 score had significant impact on the quality of life of patients(all P<0.05).Conclusion·The quality of life in patients with different subtypes of anxiety disorders is different.The anxiety level,depression level and alexithymia degree are the key variables affecting their quality of life.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

OBJECTIVE: To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR. METHODS: The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed. RESULTS: The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR. CONCLUSION Tissue engineering technology can provide a new treatment method for ATR.
Humans ; Tissue Engineering/methods* ; Tissue Scaffolds ; Rhinitis, Atrophic ; Printing, Three-Dimensional ; Cytokines

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

【Objective】 To explore the clinical value of thromboelas-tography, coagulation four items and platelet count in guiding platelet transfusion in critically ill patients. 【Methods】 A total of 188 critically ill patients in Intensive Care Unit of our hospital from January 2020 to January 2022 were selected as subjects, and were divided into study group(n=89) and the control(n=99) according to the presence of bleeding symptoms. T-test was used for comparative analysis between the two groups. Spearman was used to analyze the correlation between TEG, coagulation four items and platelet count, and binary Logistic regression analysis was used to predict the influential factors of bleeding in critically ill patients, ROC curve was used to analyze the guiding value of the above-mentioned indexes for platelet transfusion. 【Results】 1) K and PT values in the study group, above the normal range, were significantly higher than those in the control, while the Angle value, MA value, CI value, FIB value and platelet count were significantly lower than those of the control, among which MA value, CI value and platelet count were below the normal range. 2) TEG, coagulation four items and platelet count were correlated. MA and CI values were positively correlated with platelet count, instead, R and K values were negatively correlated. R value was positively correlated with PT and APTT, CI value, on the contrary, was negatively correlated, K value was positively correlated with PT, while Angle value and MA value were negatively correlated. 3) Binary Logistic regression analysis showed that decreased MA value and decreased platelet count were independent risk factors for predicting bleeding in critically ill patients(P<0.05). 4) ROC curve analysis showed that the areas under ROC curve corresponding to Angle value, MA value, CI value, FIB value and platelet count were 0.866, 0.932, 0.9, 0.838 and 0.987(P<0.05). The sensitivity was highest in platelet count and lowest in FIB. The specificity was highest in MA and lowest in Angle. Compared with the single index, the area under the curve of the combined index(K value, MA value, CI value, PT value and platelet count) was 0.995(P<0.05), Yoden index 0.944, sensitivity 100%, specificity 93.3%, all higher than the individual index. 【Conclusion】 Thromboelas-tography combined with coagulation four items and platelet count can be used to accurately predict the critically ill patients with bleeding risk. To guide clinical platelets transfusion, the combined use of indexes, including K value, MA, CI value, PT and platelet count, is superior to separate use of them as the former showed better sensitivity and specificity, demonstrating a good clinical value.