OBJECTIVES: To explore the efficacy and adverse reactions of nusinersen combined with risdiplam in the treatment of spinal muscular atrophy (SMA). METHODS: A retrospective analysis was conducted on the clinical data of 10 pediatric SMA patients treated with nusinersen combined with risdiplam at the Children's Medical Center of Xiangya Hospital, Central South University. RESULTS: Among the 10 SMA patients, there were 4 with type I, 4 with type II, and 2 with type III. Nine patients initially received nusinersen monotherapy, while 1 patient received nusinersen combined with risdiplam. The median duration of combination therapy with nusinersen and risdiplam for the 10 patients was 10.5 months (range: 0.5-20.0 months), with 6 patients undergoing combination therapy for more than 6 months, showing improvements in motor and/or respiratory function. The remaining 4 patients had combination treatment durations of 0.5, 1.0, 1.3, and 4.0 months, respectively, with no significant overall improvement. After combined treatment, 5 patients experienced skin hyperpigmentation, 2 had lumbar puncture site pain, 1 experienced vomiting, 1 had increased sputum production, and 1 had reduced total sleep time. All adverse reactions were mild and did not require medical intervention. CONCLUSIONS Nusinersen combined with risdiplam demonstrates efficacy in the treatment of SMA, and no significant adverse reactions have been observed.
Humans ; Oligonucleotides/adverse effects* ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Infant ; Muscular Atrophy, Spinal/drug therapy* ; Drug Therapy, Combination ; Child ; Azo Compounds ; Pyrimidines

OBJECTIVE: To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs. METHODS: From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected. RESULTS: In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content. CONCLUSION DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.
Antineoplastic Combined Chemotherapy Protocols ; Bone Marrow ; Decitabine/therapeutic use* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Myelodysplastic Syndromes/drug therapy* ; T-Lymphocytes, Regulatory ; Treatment Outcome

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bortezomib/therapeutic use* ; Dexamethasone ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Multiple Myeloma/drug therapy* ; Propensity Score ; Retrospective Studies ; Transplantation, Autologous/methods* ; Treatment Outcome

Video-assisted thoracoscopic surgery(VATS)has become the main method of lobectomy.Multimodal analgesia is one of the core contents of enhanced recovery after surgery(ERAS)management in VATS lobectomy,which aims to control perioperative pain,reduce stress response,and achieve rapid recovery after surgery.In recent years,multimodal analgesia has developed rapidly,emphasizing the comprehensive implementation of a variety of analgesic methods and the synergistic application of analgesics with different mechanisms.This article reviews the new progress in the implementation of multimodal analgesia in VATS lobectomy and addresses the current problems and challenges,aiming to help develop more effective and practical analgesic strategies of ERAS.
Analgesia ; Analgesics/therapeutic use* ; Enhanced Recovery After Surgery ; Humans ; Pain ; Thoracic Surgery, Video-Assisted

OBJECTIVETo differentiate patients with esophageal cancer or premalignant lesions from the high-risk population for preliminary screening of esophageal cancer using a feature index determined by a computer-aided tongue information acquisition and processing system (DS01-B).

METHODSTotally, 213 patients diagnosed with esophageal cancer or premalignant lesions and 2,840 normal subjects were collected including primarily screened and reexamined, all of them were confirmed with histological examinations. Their tongue color space values and manifestation features were extracted by DS01-B and analyzed. Firstly, the analysis of variance was performed to differentiate normal subjects from patients with esophageal cancer and premalignant lesions. Secondly, the logistic regression was conducted using 10 features and gender, age to get a predictive equation of the possibility of esophageal cancer or premalignant lesions. Lastly, the equation was tested by subjects undergoing primary screening.

RESULTSSaturation (S) values in the HSV color space showed significant differences between patients with esophageal cancer and normal subjects or those with mild atypical hyperplasia (P<0.05); blue-to-yellow (b) values in the Lab color space showed significant differences between patients with esophageal cancer or premalignant lesions and normal subjects (P<0.05). Logistic regression analysis showed that the computer-aided tongue inspection approach had an accuracy of 72.3% (2008/2776) in identifying patients with esophageal cancer or premalignant lesions for preliminary screening in high-risk population.

CONCLUSIONComputer-aided tongue inspection, with descriptive and quantitative profile as described in this study, could be applied as a cost- and timeefficient, non-invasive approach for preliminary screening of esophageal cancer in high-risk population.

Bentysrepinine (Y101), a derivative of phenylalanine dipeptide, is a novel drug candidate for the treatment of hepatitis B virus (HBV) infection. Our previous preclinical pharmacokinetic study showed that its in vivo absorption and distribution characteristics were probably related to transmembrane transport after Y101 was administered intragastically in rats. In this study, Caco-2 and MDCK-MDR1 cell models were used to investigate interactions between Y101 and P-gp through the apparent permeation coefficient (P_app) and efflux ratio (R_E); the results showed that Y101 was a substrate of P-gp. In addition, gene-transfected cell models, HEK293-hOATP1B1, HEK293-hOATP2B1 and CHO-PEPT1 were used to evaluate the affinity to OATP1B1,

Bentysrepinine (Y101), a derivative of phenyalanine dipeptide, has a novel mechanism in the treatment of hepatitis B virus (HBV) infection with a good anti-HBV effect. In the present study, a fluorometric-based high throughput method using cytochrome P450 (CYP) screening kit was adopted to evaluate in vitro inhibition potential of Y101 on CYP isoenzymes by calculating remaining enzyme activities and inhibitory potential (IC₅₀ values) using the determined values of fluorescence intensity. The result showed that Y101 exhibited little activity in the inhibition of CYP1A2, CYP3A4, CYP2C9, CYP2C19 and CYP2D6 (IC₅₀ > 100 μmol·L^-1). Y101 was used to treat human primary hepotocytes for 72 h, and the enzyme activities of CYP1A2, CYP2B6 and CYP3A4 were determined with a cocktail of probe substrates for the three CYP isoforms. The metabolites were simultaneously determined using a LC-MS/MS method. Y101 had no activity in the induction of CYP1A2, CYP2B6 and CYP3A4 on the basis of the following results:① The ratio of enzyme activities between test and control groups were all below than 1 (varied from 0.662 to 0.928); ② The induction potential of Y101 were lower than forty percent compared with that of positive groups. The above results suggest that Y101 has little activity in the regulation of metabolic drug-drug interactions based on the CYP isoform changes following co-administration of drugs.

Objective To develop an ultra?high performance liquid chromatography mass spectrometer method for the rapid determination of 8?hydroxy?2'?deoxyguanosine (8?OHdG) in human urines. Methods 8?OHdG standard solution with the concentration from 0.01 to 0.1μg/ml was formulated. The solution was implanted into ion source with a rate of 7μl/min, the mass?to?charge ratio of parent ion and product ions, and ion mass to charge ratio was identified. The mass spectrum parameters of each Ion pairs, such as DP, EP and EXP, were gradually optimized. The urine sample with a concentration of 10.0μg/L was detected, and the pH of the sample was adjusted using 1 mol/L ammonium formate and formic acid solution with a volume ratio of 5∶1, 4∶1, 3∶1, 2∶1, and 1∶1. It was tested using three different polarity of SPE, i.e.:HLB, MCX, and MAX. The elution effect of methanol and water mixture with the proportion of 90∶10, 80∶20, 50:50, 20:80, and 10:90 were tested, and then acetonitrile and water mixture with the proportion of 90∶10, 80∶20, 50∶50, 20∶80, 10∶90 were also tested. The standard curve was constructed using the ratio of a standard series application fluid concentration to corresponding compounds quantitative ion liquid concentration of the peak area. The detection limit was determined as 3 times of the signal to noise ratio corresponding to the concentration of 8?OHdG, and the quantitative lower limit was determined as 10 times of the signal to noise ratio corresponding to the concentration of 8?OHdG. The blank urine spiked recovery method was used to evaluate the precision and recovery rate. Results The mass to charge ratio of parent ion was 284.1 and the product ions was 168.1, 140.1, 123.0, and 112.0, respectively. The collision voltage of quantitative ion?pair 284.1/168.1 was 18 V, the 284.1/140.1 collision voltage was 42 V, the 284.1/123.0 collision voltage was 48 V, and the 284.1/112.0 collision voltage was 53 V. The recovery rate was the highest (87.9%-104.3%) when the pH of urine was adjusted by a 10 ml 1 mol/L ammonium formate solution, 2 ml of formic acid, 88 ml of water are mixed with the sample solution volume ratio of 1∶5, and then purified with 3 ml of methanol and 3 ml water activated HLB extraction column. Within 1.0-100.0 μg/L concentration range, 8?OHdG standard application solution test results showed a good linear relationship. The regression equation was y=1.25x+0.74, and the correlation coefficient was r=0.999 5. The detection limit was 0.2μg/L, and the limit of quantification was 0.7μg/L. The method of recovery rate was in the range of 87.9%to 104.3%, the precision was in the range from 1.5% to 3.7% and inter?assay precision was in the range from 1.6% to 5.4%. Conclusion The method developed in this study had high sensitivity, good precision and accuracy, and a wide range of testing concentrations.

Objective To develop an ultra?high performance liquid chromatography mass spectrometer method for the rapid determination of 8?hydroxy?2'?deoxyguanosine (8?OHdG) in human urines. Methods 8?OHdG standard solution with the concentration from 0.01 to 0.1μg/ml was formulated. The solution was implanted into ion source with a rate of 7μl/min, the mass?to?charge ratio of parent ion and product ions, and ion mass to charge ratio was identified. The mass spectrum parameters of each Ion pairs, such as DP, EP and EXP, were gradually optimized. The urine sample with a concentration of 10.0μg/L was detected, and the pH of the sample was adjusted using 1 mol/L ammonium formate and formic acid solution with a volume ratio of 5∶1, 4∶1, 3∶1, 2∶1, and 1∶1. It was tested using three different polarity of SPE, i.e.:HLB, MCX, and MAX. The elution effect of methanol and water mixture with the proportion of 90∶10, 80∶20, 50:50, 20:80, and 10:90 were tested, and then acetonitrile and water mixture with the proportion of 90∶10, 80∶20, 50∶50, 20∶80, 10∶90 were also tested. The standard curve was constructed using the ratio of a standard series application fluid concentration to corresponding compounds quantitative ion liquid concentration of the peak area. The detection limit was determined as 3 times of the signal to noise ratio corresponding to the concentration of 8?OHdG, and the quantitative lower limit was determined as 10 times of the signal to noise ratio corresponding to the concentration of 8?OHdG. The blank urine spiked recovery method was used to evaluate the precision and recovery rate. Results The mass to charge ratio of parent ion was 284.1 and the product ions was 168.1, 140.1, 123.0, and 112.0, respectively. The collision voltage of quantitative ion?pair 284.1/168.1 was 18 V, the 284.1/140.1 collision voltage was 42 V, the 284.1/123.0 collision voltage was 48 V, and the 284.1/112.0 collision voltage was 53 V. The recovery rate was the highest (87.9%-104.3%) when the pH of urine was adjusted by a 10 ml 1 mol/L ammonium formate solution, 2 ml of formic acid, 88 ml of water are mixed with the sample solution volume ratio of 1∶5, and then purified with 3 ml of methanol and 3 ml water activated HLB extraction column. Within 1.0-100.0 μg/L concentration range, 8?OHdG standard application solution test results showed a good linear relationship. The regression equation was y=1.25x+0.74, and the correlation coefficient was r=0.999 5. The detection limit was 0.2μg/L, and the limit of quantification was 0.7μg/L. The method of recovery rate was in the range of 87.9%to 104.3%, the precision was in the range from 1.5% to 3.7% and inter?assay precision was in the range from 1.6% to 5.4%. Conclusion The method developed in this study had high sensitivity, good precision and accuracy, and a wide range of testing concentrations.