Transcatheter aortic valve replacement(TAVR)has become one of the effective methods for treating patients with aortic valve disease.With the continuous maturity of technology,innovation of instruments and increasing experience,the indications for TAVR has been expanded.Following international trends,the number of TAVR in China has steadily increased with each passing year.In 2023,the long-term follow-up results of TAVR in low-risk AS patients further confirm the long-term benefits of TAVR.The relevant research on TAVR for patients with aortic regurgitation and patients with bicuspid aortic stenosis provide evidence support for the expansion of TAVR indications.At the same time,the development of valve devices and new technological innovations are emerging in an endless stream,and the new concept of full life cycle management is increasingly being valued.Especially in China,the development of local devices is progressing rapidly,and multiple devices have entered the clinical research stage.The clinical manifestations and research results are worth pursuing.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

OBJECTIVE: To evaluate the clinical efficacy of local infiltration anesthesia of ropivacaine combined with compound betamethasone for postoperative analgesia in patients with hallux valgus. METHODS: From September 2019 to December 2020, 48 patients with hallux valgus were treated surgically. According to different postoperative analgesia methods, the patients were divided into combined local infiltration group and intravenous analgesia pump group. There were 24 cases, in the combined local infiltration group including 2 males and 22 females;the age ranged from 21 to 78 years old, with an average of (58.3±7.7) years old;soft tissue release and chevron osteotomy were performed in 15 cases and metatarsophalangeal joint fusion in 9 cases;immediately after operation, 20 ml of ropivacaine combined with compound betamethasone mixed diluent was used for local infiltration anesthesia once. There were 24 patients in intravenous analgesia pump group, including 3 males and 21 females;the age ranged from 23 to 81 years old, with an average of(56.8±8.3) years old;soft tissue release and Chevron osteotomy were performed in 17 cases and metatarsophalangeal joint fusion in 7 cases;immediately after operation, intravenous analgesia pump was used for analgesia. The basic flow was 2 ml / h;the self control dose was 0.5 ml;and the locking time was 15 min. Visual analogue scale (VAS) was recorded at 12, 24, 48 and 72 hours after operation;and the VAS was recorded at 24 hours after operation. The occurrence of adverse drug reactions at 0 to 12 hours, 12 to 24 hours and 24 to 48 hours after operation were recorded;and the healing of incision was recorded. RESULTS: All patients were followed up, and the duration ranged from 14 to 17 days, with a mean of (14.60±0.92) days. There was significantdifference in VAS at 12, 24 and 48 hours between the combined local infiltration group and the intravenous analgesia pump group( CONCLUSION Compared with intravenous analgesia pump group, ropivacaine combined with compound betamethasone can significantly reduce postoperative wound pain without increasing adverse drug reactions, and does not increase wound infection.
Adult ; Aged ; Aged, 80 and over ; Analgesia ; Anesthesia, Local ; Bunion ; Feasibility Studies ; Female ; Hallux Valgus/surgery* ; Humans ; Male ; Middle Aged ; Pain, Postoperative/drug therapy* ; Young Adult

The College of Life Sciences (CLS) remains one of the most prestigious-and the oldest-colleges in Zhejiang University. This special issue, which includes 16 reviews contributed by our alumni and faculties, is dedicated to mark the 90th Anniversary of CLS. The reviews provide a glimpse of current progresses in the areas of life sciences such as biochemical processes and their association with diseases (Ding et al., 2019; Hu et al., 2019; Jin et al., 2019; Nie and Yi, 2019), cancer biology (Feng, 2019; Huang et al., 2019; Leonard and Zhang, 2019; Zhu F et al., 2019), plant and environmental microbiology (Li et al., 2019; Yang et al., 2019; Zhu XR et al., 2019), cell cycle (Gao and Liu, 2019; Zhang et al., 2019), RNA biology (Gudenas et al., 2019; Luo et al., 2019), and protein structural biology (Yang and Tang, 2019).

BACKGROUND: Inducing factors are currently used as a main method for the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes. OBJECTIVE: To investigate the collaborative stimulation of transforming growth factor beta1 (TGF-β1) and insulin-like growth factor 1 (IGF-1) to induce the directed differentiation of BMSCs to chondrocytes, and to explore the best inductive effect. METHODS: Rat BMSCs were isolated, cultured and purified using adherent culture. Then, different inducing factors were added in the induction medium: TGF-β1+IGF-1 group, TGF-β1 group, IGF-1 group, and control group without growth factors. Immunofluorescence was carried out at 21 days of induction. The expression of collagen type Ⅱ was evaluated by immuncytochemical staining at 7, 14 and 21 days of induction. RESULTS AND CONCLUSION: (1) Immunofluorescence detection of the TGF-β1+IGF-1 and TGF-β1 groups showed highly expressed collagen type Ⅱ (brown red-stained cytoplasm), while negatively expressed collagen type Ⅱ in the other two groups. (2) Findings from the immuncytochemical staining showed that the expression of collagen type Ⅱ was stronger in the TGF-β1+IGF-1 group than the TGF-β1 group (P < 0.01), and the expression was gradually enhanced with time. Meanwhile, there was also no expression of collagen type Ⅱ in the IGF-1 and control groups. To conclude, the combination of TGF-β1 and IGF-1 can achieve the better inductive effect on the chondrogenic differentiation of BMSCs in vitro.

Insomnia and depression are common mental disorders and there exists bidirectionality between sleep symptoms and depressive symptoms.Cognitive behavioral therapy for insomnia (CBT-I) is recommanded first in patients with accute or chronic insomnia.Phannacotherapy treatment is recommended when CBT-I is insufficient or patients are comorbided with depression or other mental diseases.Pharmacotherapy treatment options include antidepressants,benzodiazepines,non-benzodiazepines,atypical antipsychotics as monotherapy or cotherapy.The aim of the present review was to discuss the selection and clinical application of sedative-hypnotic drugs in patients with comorbid depression and insomnia.

Objective To investigate the influential factors of serum drug concentration/dosage ratio (C/D) for schizophrenia patients after oral administration of risperidone.Methods Medical records of inpatients who received oral administration of risperidone in Guangzhou Huiai Hospital during 2016 were consulted and the C/Ds were calculated.Effects of age,gender,dosage form,combined medication,comorbidity and serum concentration ratio of 9-OH risperidone and risperidone were evaluated.Results C/D in patients aged 60 or older was (10.06 ± 6.61) ng · mL-1 · mg-1 · d.It was significantly larger than those under 60 years old,which were (7.82 ± 3.31) and (8.02 ±4.05) ng · mL-1 · mg-1 · d for 40-59 and under 40 years old,respectively.In addition,C/D was decreased with the increase of 9-OH risperidone/ risperidone ratio.The C/D were(10.96 ±6.46),(8.71 ±4.45)and (6.30 ± 2.99) ng · mL-1 · mg-1 · d for 9-OH risperidone/risperidone ratio ＜ 1,1-10 and ＞ 10,respectively.Gender,dosage form andthe major combined medications and comorbidities in the recruited patients hardly affected the C/D of oral risperidone.Conclusion The dose of risperidone that administered to the aged should be reduced properly.Serum concentration ratio of 9-OH risperidone and risperidonehas a potential to be used as an indirect index of the activity of metabolic enzymes.

Objective To evaluate the uncertainty in the determination of lamotrigine (LTG) in human serum with high performance liquid chromatography (HPLC).Methods It was analyzed that the influences of various factors for detection results,including weighing,solution preparation,serum extraction,calibration curve fitting repeatability and so on.The expanded uncertainty was evaluated and combined by each component of uncertainty.Results The expanded uncertainty of lamotrigine at low (1.50 μg · mL-1),middle (8.00 μg · mL-1),high (20.00 μg · mL-1) concentrations were UL =0.30,UM =0.53,UH =0.98,respectively (P =95％,k =2).The corresponding test concentration were (1.51 ±0.30),(8.22±0.53),(20.40±0.98) μg · mL-1,respectively.Conclusion The relative uncertainty on the determination of lamotrigine in human serum by HPLC was mainly caused by repeatability,calibration curve fitting and extraction recovery;repeatability and calibration curve fitting were the important factor in influencing the results of low concentrations.

OBJECTIVETo establish a new function method for the analysis of a-fetoprotein (AFP) and beta-hCG in testicular tumors.

METHODSWe reexamined the serum levels of AFP and beta-hCG after radical orchiectomy, and calculated the measured coordinate, with the abscissa representing the number of the half-lives of tumor markers, and the ordinate representing the measured value of tumor markers. Referring to the measured value of tumor markers before surgery as a, the number of half-lives as x, and their theoretical value over a period of x elimination half-lives as y (logarithm to the base 2 of y), we calculated the predicted coordinate according to the formula y = log2(a/2x) ==> x + y = log2a (function 1). Then we assessed tumor residue and metastasis by analyzing the relationship between the measured and predicted coordinates.

RESULTSThe pathological examination of case 1 revealed a germ cell tumor of a mixed histological pattern of syncytiotrophoblast and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.22, 6.21) and (10, 8.38), and the predicted coordinates (2.22, 6.34) and (10, 4.41) , indicating the elimination of the yolk sac tumor and metastasis of the syncytiotrophoblast tumor. Case 2 demonstrated the mixed pathological nature of teratocarcinoma and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.67, -1.03) and (12, -3.32), and the predicted coordinates (2.67, 1.41) and (12, -5.80). But the review times of AFP and beta-hCG were out of the effective range of half-lives, with the measured values below the normal, which suggested no tumor residue or metastasis. Case 3 was found to be embryonal carcinoma. The measured coordinate of AFP was (0.22, 9.25) , and the predicted coordinate (0.22, 9.55) , indicating the elimination of tumor.

CONCLUSIONThe change of the tumor markers predicted by the function method coincided with the natural course of disease in the three cases. The coincidence of the measured with the predicted coordinate after radical orchiectomy indicates no metastasis, while their disagreement suggests possible residue and metastasis of the tumor.

Adult ; Biomarkers, Tumor ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; blood ; Humans ; Male ; Models, Statistical ; Orchiectomy ; Testicular Neoplasms ; metabolism ; pathology ; alpha-Fetoproteins ; analysis

OBJECTIVETo explore the effects of bisphenol A (BPA) exposure on toxicity characteristic and OCT4 and SOX2 gene expression of mouse embryonic stem cells (mESC).

METHODSmESC were cultured, and treated with the doses of 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L respectively of BPA and DMSO (the solvent control group)for 24 hours, and three groups of cells were treated with the same method. The morphological changes of mESC in the control and exposure groups were observed through an inverted microscope. Cell counting kit 8 (CCK8) was used to detect the effects of BPA on proliferation of mESC, and based on the results, the half inhibitory concentration (IC50) was calculated. Real-time fluorescent quantitative polymerase chain reaction (RT-QPCR) and western blotting were used to detect the expression of OCT4 and SOX2.

RESULTSBPA had certain toxicity on mESC, the treatment of BPA significantly increased cell toxicity in a concentration-dependent manner, and the IC50 was 4.3×10(-4) mol/L, combined with the BPA exposure concentration of the environment and the related literature, eventually taking the five concentrations of 10(-8), 10(-7), 10(-6), 10(-5), 10(-4) mol/L as the experimental groups. The mESC morphology were effected after the treatment of BPA for 24 h, compared with the control group, the number of cells decreased, appearing some floating cells, and the cell cloning became irregular and differentiation in the higher concentration groups. The OCT4 mRNA expression level in the 10(-7) mol/L (1.146 ± 0.087), 10(-6) mol/L (1.156 ± 0.030), 10(-5) mol/L (1.158 ± 0.103) and the 10(-4) mol/L (1.374 ± 0.053) dose group were all significantly higher than the control group (1.000 ± 0.000) (t values were -2.384, -2.953, -3.203, -4.021 respectively, P value all < 0.05). Meanwhile, the SOX2 mRNA expression level in the 10(-4) mol/L (1.113 ± 0.052) were higher than the control group (1.000 ± 0.000) (t value was -2.765, P value < 0.05). Moreover, the OCT4 protein expression level in the 10(-5) mol/L (1.360 ± 0.168) and 10(-4) mol/L (1.602 ± 0.151) were all significantly higher than the control group (1.000 ± 0.000) (t values were -3.538, -4.002 respectively, P value all < 0.05), while no obvious change of the SOX2 protein expression level was detected in all treated groups.

CONCLUSIONBPA in a certain dose range could upregulate the expression of OCT4 gene in mouse embryonic stem cells while had no significant effect on the expression of SOX2 gene.

Animals ; Benzhydryl Compounds ; toxicity ; Cells, Cultured ; Embryonic Stem Cells ; drug effects ; metabolism ; Gene Expression ; Mice ; Octamer Transcription Factor-3 ; genetics ; Phenols ; toxicity ; SOXB1 Transcription Factors ; genetics ; Signal Transduction ; drug effects