Adult ; Aged ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/diagnosis* ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia/diagnosis* ; Pneumonia, Viral/diagnosis* ; Retrospective Studies ; SARS-CoV-2

Objective:To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features.Methods:Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed.Results:Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age ( P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions:Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

OBJECTIVE: To study the significance of dishevelled (DVL) proteins in the Wnt signaling pathway in the pathogenesis and prognosis of childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 33 children with new-onset ALL were enrolled as the case group. According to the degree of risk, they were divided into 3 groups: low-risk (n=14), intermediate-risk (n=5) and high-risk (n=14). A total of 29 children with immune thrombocytopenia were enrolled as the control group. At diagnosis and on day 33 of induction therapy, 2 mL bone marrow samples were collected from the case and control groups, and qRT-PCR was used to measure the mRNA expression of DVL1, DVL2 and DVL3 in blood cells of bone marrow. RESULTS: The mRNA expression of DVL1, DVL2 and DVL3 in the case group in the incipient stage was significantly higher than that in the remission stage and the control group (P<0.05). Compared with the control group, the case group had a significant increase in the mRNA expression of DVL2 in the remission stage (P<0.05). The mRNA expression of DVL2 was significantly higher than that of DVL1 and DVL3 in both remission and incipient stages (P<0.05). The high- and intermediate-risk groups had significantly higher mRNA expression of DVL1 and DVL2 than the low-risk group (P<0.05). The mRNA expression of DVL2 was significantly higher than that of DVL1 and DVL3 in the low-, intermediate- and high-risk groups (P<0.05). CONCLUSIONS The change in the expression of DVL, especially DVL2, in the Wnt signal pathway has certain significance in the pathogenesis and prognosis of childhood ALL.
Child ; Dishevelled Proteins ; Humans ; Phosphoproteins ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Wnt Signaling Pathway

This paper summarizes research progresses of Chinese scholars in the field of drug metabolism and pharmacokinetics (DMPK) in 2018. Chinese scholars focused on drug metabolizing enzymes and transporters, and carried out studies on the mechanisms of drug metabolism and transport of active molecules. Topics of research included regulatory mechanisms of drug metabolizing enzymes or transporters, and their implications in drug development and disease etiology or progression. Here, we summarized studies on drug toxicity based on drug metabolism or transport, rational drug use in the clinic, drug metabolism mediated by intestinal flora, metabolism of traditional Chinese medicines, and new technologies or models in DMPK. In recent years, the research focus of drug metabolism in China has transformed from serving for new drug discovery and rational use, to innovation driven and mechanism oriented research. The domestic research topics and technology utilization are gradually aligning with the international conventions.

OBJECTIVE: To evaluate the safety and efficacy of the seven-step two-lobe holmium laser enucleation of the prostate (HoLEP) technique with low power laser device, and to introduce the detailed operating procedures, key points, short-term outcomes of this modified HoLEP technique. METHODS: From March 2016 to November 2017, 90 patients underwent HoLEP in Peking University Third Hospital. The patients were divided into two groups: high-power group (32 patients) were performed with traditional Gilling's three-lobe enucleation using high power (90 W) laser; Low-power group (58 patients) were performed with seven-step two-lobe enucleation using low power (40 W) laser. The main steps of the low power seven-step two-lobe HoLEP phase included: (1) The identification of the correct plane between adenoma and capsule at 5 and 7 o'clock laterally to the veru montanum; (2) The connection of the bilateral plane by making a adenoma incision at the proximal point of veru montanum; (3) The extension of the dorsal plane under the whole three lobes between adenoma and capsule towards the bladder neck; (4) The separation of the middle lobe from two lateral lobes by making two retrograde incisions separately from apex 5 and 7 o'clock towards the bladder neck; (5) The enucleation of the middle lobe adenoma by extending the dorsal plane through into the bladder; (6) The prevention of the apex mucosa by making a circle incision at the apex of the prostate; (7) The en-bloc enucleation of the two lateral lobe adenomas by extending the lateral and ventral plane between adenoma and capsule from 5 and 7 o'clock to 12 o'clock conjunction and through into the bladder. RESULTS: The mean patient age was (66.25±5.37) years vs. (68.00±5.18) years; The mean body mass indexes were (24.13±4.06) kg/m² vs. (24.57±3.50) kg/m²; The mean prostate specific antigen values were (3.23±2.47) μg/L vs. (6.00±6.09) μg/L; The average prostatic volumes evaluated by ultrasound was (49.03±20.63) mL vs. (67.55±36.97) mL. There was no significant difference between the two groups. Furthermore, there were no significant differences in terms of perioperative and follow up data, including operative time; enucleation efficiencies; hemoglobin decrease; blood sodium and potassiumthe change postoperatively; catheterization duration and hospital stay; the international prostate symptom scores and quality of life scores pre- and post-operatively. There was 1 transurethral resection of the prostate (TURP) conversion in high-power group and 1 transfusion in low-power group during the operations. The follow-up one month after operation showed no severe stress incontinence in both the groups, whereas 3 cases ejaculatory dysfunctions in high-power group versus 1 case in low-power group were observed; Other surgeryrelated complications included: 2 cases postoperative hemorrhage (Clavien II and Clavien IIIb) in high-power group, 2 cases postoperative temperature more than 38 °C (Clavien I) and 1 case dysuria following catheter removal (Clavien I) in low-power group. CONCLUSION Low power laser device can be applied safe and effectively for HoLEP procedure using the seven-step two-lobe HoLEP technique. The outcomes comparable with high power laser HoLEP can be achieved.
Holmium ; Humans ; Laser Therapy ; Lasers, Solid-State ; Male ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Transurethral Resection of Prostate ; Treatment Outcome

Objective To evaluate the survival and prognostic factors of esophageal cancer treated with definitive ( chemo ) radiotherapy by applying novel radiation techniques including three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT). Methods Clinical data of 2762 patients with non-operated esophageal squamous cell carcinoma who underwent definitive ( chemo ) radiotherapy from 2002 to 2016 in 10 hospitals were retrospectively analyzed.The prognostic factors were also identified and analyzed. Results The median follow-up time was 60. 8 months. The 1-, 2-, 3-and 5-year overall survival (OS) of all patients was 71. 4％,48. 9％,39. 3％,and 30. 9％,respectively.The 1-,2-,3-and 5-year progression-free survival (PFS) was 59.5％,41.5％,35.2％,and 30％,respectively.The median survival was 23 months.The median time to progression was 17. 2 months.Multivariate analysis demonstrated that age, primary tumor location, clinical stage, tumor target volume, EQD2 and treatment mode were the independent prognostic factors for OS.Primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS. Conclusions In this first large-scale multi-center retrospective analysis of definitive ( chemo) radiotherapy for esophageal squamous cell carcinoma in China, the 5-year OS of patients with esophageal squamous cell carcinoma is significantly improved by 3DCRT, IMRT combined with chemotherapy drugs. However, the findings remain to be validated by prospective clinical trials with high-level medical evidence.

Background: Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study. Methods: TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54). Results: Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning. Conclusions: Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China. Trial Registration ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China ; Crotonates ; administration & dosage ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Administration Schedule ; Humans ; Immunosuppressive Agents ; administration & dosage ; adverse effects ; therapeutic use ; Multicenter Studies as Topic ; Multiple Sclerosis ; drug therapy ; metabolism ; Proportional Hazards Models ; Toluidines ; administration & dosage ; adverse effects ; therapeutic use