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 investigate the classification,clinical manifestations,diagnosis,differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.Methods Hospital ethical approval and patient informed consent were obtained.We report a case of oral lichenoid lesion in children and review the diagno-sis and treatment of oral lichenoid damage in the literature.Results The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years.There was a large area of tongue back surface erosion with an irregular shape,surrounded by pearly-white lines.The left erosive area was accompanied by tissue hyperplasia,which was approximately 1.5 cm × 2.0 cm,with tough texture and broad masses.The pathological diagnosis of the pa-tient was oral lichenoid lesion.After biopsy of the dorsal surface of the tongue,the pathological diagnosis of the patient was granulomatous inflammation.The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features,systemic history,medication history and histopathological findings.A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus,oral lichenoid drug reactions,oral lichenoid contact damage and chronic ulcerative stomatitis.The clini-cal treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.Conclusion There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions.They rely mainly on history tak-ing,clinical manifestations and histopathological findings,and the treatment is mainly based on the topical and/or sys-temic use of glucocorticoids.

Celastrol is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook.f..It is a kind of traditional Chinese medicine monomer with extensive pharmacological activity and has anti-tumor,anti-inflammation,anti-oxidation and neuroprotective effects.Studies have found that celastrol is not only closely related to obesity,tumor and cardiovascular diseases,but also plays a neuroprotective role in the cerebrovascular system by regulating various signaling pathways.At present,effective drugs for stroke are still limited,but with the deepening of the research on celastrol,its therapeutic potential in stroke has received more and more attention,especially in ischemic and hemorrhagic stroke,which has shown good therapeutic effects.Therefore,this is the first time to systematically summarize the therapeutic effects of celastrol on stroke and the underlying mechanisms involved,in order to provide further directions and references for the neuroprotective effects of celastrol.

Objective:To investigate the diagnostic value of serum Aspergillus fumigatus immunoglobulin G (IgG), bronchoalveolar lavage fluid (BALF) galactomannan antigen test (GM test) and combined detection of the two methods in chronic pulmonary aspergillosis (CPA). Methods:A total of 310 patients with suspected CPA who were hospitalized in Wuhan Pulmonary Hospital from January 2020 to December 2022 were screened. BALF-GM test and serum Aspergillus fumigatus IgG were detected. According to the inclusion and exclusion criteria, 151 confirmed or clinically diagnosed CPA patients were enrolled and 60 non-CPA cases were included as controls. The underlying diseases, clinical symptoms and imaging findings of the two groups were analyzed using case-control study. Statistical comparison was performed by chi-square test. The efficacies of BALF-GM test, serum Aspergillus fumigatus IgG test, and their combined detection for CPA were analyzed by receiver operating characteristic curve. Results:There were 130 confirmed cases and 21 clinically diagnosed cases among 151 patients with CPA, including 106 males (70.2%) with age of (54.6±15.5) years. The age of 60 non-CPA patients was (53.6±17.8) years, including 42 males (70.0%). The proportions of pulmonary tuberculosis, bronchiectasis and chronic obstructive pulmonary disease, and the incidence of hemoptysis in CPA group were 79.47%(120/151), 86.09%(130/151), 26.49%(40/151) and 43.71%(66/151), respectively, which were all higher than those in non-CPA group (10.00%(6/60), 25.00%(15/60), 8.33%(5/60) and 11.67%(7/60), respectively), and the differences were statistically significant ( χ2=86.14, 74.56, 8.44 and 19.48, respectively, all P<0.05). The proportion of interstitial lung disease in non-CPA group was 28.33%(17/60), which was higher than that in CPA group (2.65%, 4/151), and the difference was statistically significant ( χ2=31.61, P<0.001). The common imaging findings of CPA patients were pulmonary cavity (70.86%, 107/151), cavity inclusions (41.72%, 63/151) and lung damage (33.77%, 51/151). The specificity and sensitivity of serum Aspergillus fumigatus IgG for CPA diagnosis were 81.7% and 68.9%, respectively, and the area under the curve (AUC) was 0.753 (95% confidence interval (95% CI) 0.681 to 0.825, P< 0.001). The specificity and sensitivity of BALF-GM test were 76.7% and 67.5%, respectively, and the AUC was 0.724 (95% CI 0.649 to 0.800, P<0.001). The specificity and sensitivity of the two methods in series combined detection were 95.0% and 44.4%, respectively, and those of the two methods in parallel detection were 60.3% and 94.5%, respectively. The AUC of the combined diagnosis of CPA by the two methods was 0.843 (95% CI 0.783 to 0.903, P<0.001). Conclusions:Serum Aspergillus fumigatus IgG combined with BALF-GM test has a good diagnostic efficacy for CPA. The detection of serum Aspergillus fumigatus IgG is non-invasive and highly specific, which is beneficial to the early diagnosis and treatment of CPA.

【Objective】 To explore the perioperative blood management in patients with pancreatic pseudocyst combiend with coagulation factor Ⅴ(FⅤ) deficiency. 【Methods】 Preoperative: In order to determine the effect of cryoprecipitated antihemophilic factor and fresh frozen plasma (FFP) on the elevation level of factor Ⅴ, we alternately infused cryoprecipitate and FFP in the resting state. TEG, coagulation function and coagulation factor activity were monitored before and 1 h, 24 h and 48 h after infusion, and intraoperative and postoperative blood transfusion strategies were formulated. FFP 600 mL and cryoprecipitate 10 U were supplemented preoperatively. Intraoperative: The operation procedure was performed for 7 hours with an infusion of 600 mL FFP without significant bleeding. Postoperative: FFP was infused. 【Results】 Preoperative: The coagulation factor Ⅴ activity on pre-operation was 1.9% and 1.8%. After alternating infusion cryoprecipitate 10 U and FFP 1 200 mL, the FⅤactivity increased to 5.1% and 6.0%, respectively. There was no significant difference in TEG parameters, PT and ATPP results were decreased to varying degrees. Intraoperative: The operation was successful without obvious bleeding. Postoperative: FFP 500 mL was infused 2 h after operation, and FFP 250-500 mL was injected daily from 1 to 7 days after surgery. No significant bleeding was observed in the wound, the results of TEG, PT, APTT and hemoglobin (Hb) did not change significantly compared with those before surgery. The patient was discharged successfully 12 days after surgery. The genetic test results showed that he had inherited coagulation factor Ⅴ deficiency, which was a compound heterozygous variation. 【Conclusion】 Perioperative blood management in patients with FⅤ deficiency combined with surgical disease, requiring pre-transfusion evaluation and post-transfusion evaluation in combination with laboratory investigations and clinical manifestations, cryoprecipitate and fresh frozen plasma can be effective in supplementing coagulation factors. The TEG seems to be better than the Seven items of coagulation function in judging the clotting status of patients with FⅤ deficiency.

Metabolic reprogramming, such as abnormal utilization of glucose, addiction to glutamine, and increased de-novo lipid synthesis, extensively occurs in proliferating cancer cells, but the underneath rationale has remained to be elucidated. Based on the concept of the degree of reduction of a compound, we have recently proposed a calculation termed as potential of electron transfer (PET), which is used to characterize the degree of electron redistribution coupled with metabolic transformations. When this calculation is combined with the assumed model of electron balance in a cellular context, the enforced selective reprogramming could be predicted by examining the net changes of the PET values associated with the biochemical pathways in anaerobic metabolism. Some interesting properties of PET in cancer cells were also discussed, and the model was extended to uncover the chemical nature underlying aerobic glycolysis that essentially results from energy requirement and electron balance. Enabling electron transfer could drive metabolic reprogramming in cancer metabolism. Therefore, the concept and model established on electron transfer could guide the treatment strategies of tumors and future studies on cellular metabolism.
Electrons ; Energy Metabolism ; Glucose ; Glycolysis ; Humans ; Neoplasms

【Objective】 To explore the effect of allogeneic platelet gel on hemostasis and repair of vascular anastomoses and wounds in patients with giant aortic aneurysms during surgery. 【Methods】 One adult dose of allogeneic platelets, applied as platelet rich plasma (PRP), was prepared as platelet gel (PG) (about 220 mL) for spraying or smearing at the vascular anastomosis and thoracic wound during the surgery of giant aortic aneurysms. 【Results】 The gel formation was presented about 30 seconds after spraying or smearing with PG on the anastomotic and wound surface. The hemostatic effect is good, with less postoperative drainage fluid from pericardium and mediastinum than usual, and the ICU stay was 4 days. 【Conclusion】 Allogeneic platelets as a source of PRP to prepare PG may be applied to obtain the clotting and healing during surgical operation.

Objective:In this study, we aimed to determine the change and clinical significance of serum level Apo A1 in MM patients.Methods:In total, 412 multiple myeloma patients were examined. SPSS 22.0 was used for data analysis. Correlation analysis was performed using linear correlation or Spearman rank correlation coefficients. Measurement data were analyzed with the t-test, Mann-Whitney U-test, or oneway analysis of variance (ANOVA) . Used the ROC curve to calculate the cutoff value and compared the OS and PFS between high Apo A1 subgroup and low Apo A1 subgroup with Kaplan-Meier survival analysis.Results:Our study showed that value of Apo A1 in the patient group was lower than that in the control group (0.89 g/L vs 1.24 g/L, P<0.05) . We found that Apo A1 dynamically changed with different MM stages. As it was increased when the disease was in remission, and decreased after disease in progression. According the result of multivariate analysis Apo A1 reduction become the independent risk factors of MM. On the basis of Kaplan-Meier survival analysis between high Apo A1 subgroup and low Apo A1 subgroup, we found higher Apo A1 patienta had longer OS rate and PFS. Conclusions:Apo A1 is a useful biomarker of tumor burden and a prognostic factor of multiple myeloma.

Objective:To analyze the clinical characteristics of intestinal tuberculosis improving the diagnosis rate of intestinal tuberculosis.Methods:From January 2014 to June 2018, at Wuhan Pulmonary Hospital, the data of clinical symptoms, laboratory examination, imaging, endoscopy, surgery and pathological examination of 205 patients with intestinal tuberculosis were retrospectively analyzed. Descriptive analysis was performed for statistical analysis.Results:Among 205 patients with intestinal tuberculosis, 145 cases were male and 60 cases were female, aged 14 to 85 years old. A total of 189 cases (92.2%) were complicated with lung tuberculosis, of which 151 cases (79.9%) were positive for sputum acid fast staining. A total of 126 cases were tested for feces acid fast staining, of which 83 cases (65.9%) were positive. A total of 60 cases (29.3%) were tested for GeneXpert Mycobacterium tuberculosis/rifampicintablet (GeneXpert MTB/RIP), of which 49 cases (81.7%) were positive. A total of 44 cases of intestinal tuberculosis were diagnosed by biopsy under electronic enteroscopy, and 21 cases were pathologically diagnosed with intestinal tuberculosis after surgical resection. The 21 patients were tested for GeneXpert MTB/RIP, of which 19 cases (90.5%) were positive and 10 cases (47.6%) were positive for tuberculin test. Six patients were clinically diagnosed with intestinal tuberculosis after effective treatment of antituberculosis drugs. Conclusions:Combination of clinical symptoms and laboratory, imaging, endoscopic and pathological examination, as well as the therapeutic effect of diagnostic antituberculosis treatment could make comprehensive diagnosis of intestinal tuberculosis. The GeneXpert MTB/RIP examination is of great value in the diagnosis of intestinal tuberculosis.

Objective To analyze the effect of long-term anti-viral treatment in children with acquired immune deficiency syndrome (AIDS) and investigate the factors affecting the treatment efficacy and growth and development of the children, so as to provide reference for improving the efficacy of antiviral drugs.Methods Children with AIDS receiving anti-retroviral treatment during 2004 to 2016 were retrospectively enrolled.The height, weight and CD4+ T cell counts were recorded every half year and the measurement of HIV RNA load was recorded on an annual basis.The CD4+ T cell counts and viral inhibition rates for the children who were under the treatment in the first year, 1~<5 years, 5~<10 years, and ≥10 years were compared.And their growth and development were also assessed.Treatment efficacy and growth and development of the children were compared between those who raised by social organization and by family.Children who raised by family were further divided into two groups: high-income and low-income groups.All categorical data were analyzed using chi-square test and those non-normal distribution were compared by rank-sumtest.Results After comparison between the children who have received anti-virus treatment for 1 to 5 years (including 5 year) and those for 5 to 10 year (including 10 years), the baseline CD4+ T cell counts were 436.5(265, 728)cells/μL and 334 (102, 535)cells/μL, respectively with the statistically significant difference (Z=-2.619, P<0.01).The last measured CD4+ T cell counts were 779 (622, 1 024)cells/μL and 720 (640, 977)cells/μL, respectively with no statistical significance (Z=-0.708, P>0.05);and viral inhibition rates were 92.9% and 97.6%, respectively with no statistical significance (χ2=1.071, P>0.05).The viral inhibition rate for the children receiving the treatment for 1 year was 85.7%, while that for whose treatment lasted for more than 10 years was 100.0%.A total of 5 cases developed drug-resistance (2 cases treated for 1 to 5 years and 3 cases for 5 to 10 years), and the virus replication was completely inhibited after switching to Lopinavir/ritonavir (LPV/r).The drug compliance was more than 95.0%.64.8% of children met the standard height, while 68.5% met the standard body mass.The baseline and last measured CD4+ T cell counts showed no significant differences between family-raised and social organization-raised children (Z=-1.159 and -0.523, respectively, both P>0.05).The children from high-income families had no significant differences compared with those from low-income ones in terms of the baseline and last measured CD4+ T cell counts (Z=-0.019 and -0.776, respectively, both P>0.05).Conclusions The long-term anti-retroviral treatment can effectively elevate the CD4+ T cell counts, inhibit viral replication and ensure drug compliance, which may promote the growth and development of children.However, approximately 30% children are still lower than the normal standards in terms of height and body mass.The drug-taking observer plays a central role on treatment effect.Most of the children′s family suffer from poor economic conditions.