Objective:To compare safety and efficacy of one-stage laparoscopic common bile duct exploration plus laparoscopic cholecystectomy (LCBDE+ LC) with endoscopic retrodrade cholangiopancreatography plus laparoscopic cholecystectomy (ERCP+ LC) in elderly patients with concomitant gallbladder and common bile duct (CBD) stones.Methods:This is a two-center retrospective study with clinical data on 492 patients aged over 80 years diagnosed with concomitant gallbladder and CBD stones treated between January, 2014 and December, 2020 at The First Affiliated Hospital of Wenzhou Medical University and Quzhou Hospital Affiliated to Wenzhou Medical University. There were 254 males and 238 females, aged (83.9±3.0) years. These patients were divided into two groups based on their operative methods: the one-stage group (LCBDE+ LC, n=186) and the two-stage group (ERCP+ LC, n=306). Differences in surgery, stones and hospitalization costs were compared between the two groups. Results:When compared with the ERCP+ LC group, the LCBDE+ LC group had significantly higher incidences of previous gastrectomy [21.5%(40/186) vs 4.2%(13/306)], multiple stones [77.4%(144/186) vs 49.3%(151/306)], larger stone diameter [13.7(6.4, 18.6)mm vs 10.9(5.7, 16.1) mm], and increased hospitalization expenditure [(2.37±0.31) Wanyuan vs (3.26±0.44) Wanyuan] (all P<0.05). However, the rates of residual stone [2.7%(5/186) vs 1.3%(4/306)], stone recurrence [2.2%(4/186) vs 5.2%(16/306)], postoperatively overall complications [3.2%(6/186) vs 1.3%(4/306)], and total hospital stay [(10.7±6.2) d vs (11.3±5.4) d] were not significantly different between the two groups (all P>0.05). Conclusions:Allowing for the similar safety and effectiveness, and lower hospitalization expenditure, LCBDE+ LC was a preferred choice for patients aged over 80 year, especially in patients who had previous gastrectomy, multiple large CBD stones, or who could not accept endoscopic procedures for treatment of CBD stones.

Objective:To explore the expression of indoleamine 2, 3-dioxygenase 1(IDO-1), lymphocyte-activation gene 3 (LAG-3) and T cell immunoglobulin domain and mucin domain-containing molecule 3 (TIM-3) in differentiated thyroid cancer (DTC), and the value of them on prognosis.Methods:From May 2014 to November 2015, 119 DTC patients (33 males, 86 females, media age: 42 years) who underwent surgical treatment in Shanghai Sixth People′s Hospital were retrospectively analyzed. The expressions of IDO-1, LAG-3 and TIM-3 in the specimens were analyzed by immunohistochemistry and the expression differences between cancer tissues and normal tissues were analyzed by χ2 test. The correlation of IDO-1, LAG-3 and TIM-3 with clinical characteristics were analyzed using logistic regression analysis. The patients were followed up for 5 years, and the relationships of the progression-free survival (PFS) rate with the expressions of the three immune checkpoints were analyzed by Kaplan-Meier method, log-rank test and Cox proportional hazard models. Results:The overall 5-year PFS rate for 119 DTC patients (median follow-up time: 55(2-66) months) was 76.47%(91/119). The positive expression rates of LAG-3 and TIM-3 in cancer tissues were 21.85%(26/119) and 78.15%(93/119) respectively, which were significantly higher than those in normal thyroid tissues (7.34%(8/109) and 62.39%(68/109); χ2 values: 9.43, 6.81, both P<0.05). While the positive expression rate of IDO-1 was 70.59%(84/119) in cancer tissues, which did not show a significant difference from that in normal thyroid tissues (64.22%(70/109); χ2=1.05, P>0.05). Factors associated with the positive expression of LAG-3 included tumors with a single lesion (odds ratio ( OR)=0.248, 95% CI: 0.086-0.716, P=0.010). Log-rank test ( χ2=4.96, P=0.026) and multivariate Cox regression analysis (hazard ratio ( HR)=2.239, 95% CI: 1.013-4.592, P=0.046) suggested that LAG-3 positive expression was an independent risk factor of PFS. The same analysis of TIM-3 found no clinicopathological factors related to TIM-3 positive expression ( OR: 0.309-3.084, all P>0.05) and no association between TIM-3 positive expression and PFS ( χ2=0.008, P=0.929). Conclusion:The expressions of LAG-3 and TIM-3 are significantly increased in DTC tissues, and the higher expression of LAG-3 is associated with the worse prognosis, suggesting that LAG-3 may be a potential target for immunotherapy in DTC patients.

Objective:To explore the efficacy of percutaneous osteoplasty (POP) combined with 131I therapy in patients with bone metastases from differentiated thyroid carcinoma (DTC) and assess the survival. Methods:From Januray 2008 to January 2020, 29 DTC patients with bone metastases (16 males, 13 females, age range: 24-64 years) who received POP combined with 131I therapy in Shanghai Sixth People′s Hospital were retrospectively analyzed. Clinical data and characteristics of patients were analyzed. The efficacy and prognosis were evaluated based on the changes of serum thyroglobulin (Tg) and relieving condition of bone pain after the combined treatment. χ2 test was used to determine the association between clinical characteristics and efficacy, and Kaplan-Meier analysis was used to estimate the overall survival (OS) rate. Results:The biochemical response rate of serum Tg was 68.97% (20/29) after the combined treatment. For the influence on changes of serum Tg, whether or not combined with non-osseous distant metastasis, and cumulative dose of 131I treatment(≥22.2 vs <22.2 GBq) were statistically significant ( χ2 values: 5.448 and 4.371, both P<0.05). The rate of bone pain relief was 65.52%(19/29). Age (≥55 vs <55 years) and the cumulative dose of 131I treatment had statistically influences on bone relief ( χ2 values: 7.486 and 5.154, both P<0.05). The 5-years OS rate of patients was 87.68%, while the 10-years OS rate was 65.76%. Conclusion:POP combined with 131I therapy is effective on relieving the pain, reducing the serum Tg to some extent, and improving the long-term survival of DTC patients with bone metastasis.

Endocrine therapy is one of the standard treatment options for breast cancer which plays an important role in treating patients with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer.However,some patients develop resistance during therapy due to factors such as tumor heterogeneity,which is particularly acute in the treatment of advanced breast cancer.Based on aiming at a rational and effective treatment,some clinical trials recently have demonstrated that compared to endocrine therapy alone,cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy can significantly improve the prognosis of ER-positive,HER2-negative advanced breast cancer.Its main products are Palbociclib,Ribociclib and Abemaciclib.This review mainly focuses on the mechanism and related clinical trials of CDK4/6 inhibitor inhibitors in ER-positive,HER2-negative advanced breast cancer.

Objective: To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases, and to provide more useful guidance information for the clinic practice. Methods: A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poiso-ning in Children′s Hospital, Chongqing Medical University from January 2014 to December 2016, were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way, dysfunction organs and poison concentration were studied respectively. Results: (1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg/L (55-4 654 μg/L). Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L). Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L), respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning, 16 cases with dermal poisoning, while 23 cases denied any involved ways of poisoning, and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r=0.619, P<0.01). (5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P>0.05). Conclusions The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is, the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.

Objective: To evaluate whether the self-designed single-channel intracavitary applicator yields equivalent clinical efficacy and safety to the standard Fletcher-type three-channel applicator in the high-dose-rate (HDR) brachytherapy for uterine cervical cancer. Methods: From December 2011 to April 2017, patients initially diagnosed with cervical cancer were randomly assigned into the external beam radiotherapy (EBRT)+ single-channel intracavitary applicator group (the patent single-channel group) and EBRT+ the Fletcher applicator group. Whole pelvis irradiation was delivered with 6-MV photons via a four-field box variant or anterior and posterior parallel fields. Five to six fractions of intracavitary brachytherapy were performed at a dose of 7 Gy at point A once a week after 30 Gy (BED at point A: 80-90 Gy). Chemotherapy was given with intravenous injection of cisplatin at a dose of 40 mg/m² once weekly during EBRT.Clinical efficacy and safety were evaluated after the treatment. Results: In total, 150 eligible cases were assigned into the Fletcher applicator group and 149 cases into the patent single-channel group. The short-term clinical efficacy and acute toxicity did not significantly differ between two groups. The response rate was 94.0% in the Fletcher group, and 94.7% in the patent single-channel group. In the Fletcher applicator group, 76(50.7%) patients developed ≥ grade 3 hematologic toxicity and 61(40.9%) in the patent group (P=0.195). Conclusions: The self-designed patent single-channel intracavitary applicator yields equivalent clinical efficacy and safety (acute toxicity) to the standard Fletcher-type three-channel applicator in the HDR brachytherapy for uterine cervical cancer. Clincal Trial Registration Chinese Clinical Trial Registry (ChiCTR-TRC-12002321).

[Objective]To compare and contrast the dosimetry between Tomo planning and BrainLab planning for lung metasta-ses in stereotactic body radiation therapy(SBRT).[Methods]Four Patients with one,two,three and four metastases were selected. The PTV is 2.89 ± 1.15 cm3. Two plannings with total dose of 50 Gy to cover 95% of PTV ,5 Gy/Fraction and 10 fractions were designed using Tomo planning system and BrainLab planning system respectively. The DVH curves of spinal cord ,both lungs and normal tissue were compared. The conformity index andhomogeneityindex were analyzed as well.[Results]The homogeneity index (HI)and conformity index(CI)of the targets in Tomo planning system were 1.0314 ± 0.0700 and 0.687 ± 0.075,respectively. In BrainLab planning system the HI and CI of the targets were 1.0764 ± 0.1241 and 0.571 ± 0.042,respectively. To HI the P value in T test was less than 0.01 and the HI was better in Tomo than BrainLab and so was CI. The dose to spinal cord was higher in BrainLab planning system than that in Tomo. The dose to nomal tissue and both lungs were not different in the two planning systems and V20 of lung is as small as 10%.[Conclusions]For small volume lung metastases which longest diameter were less than 4 cm,the tomotherapy should be better choice.

OBJECTIVE:To understand the situation of essential medicines and promote their rational use in our hospital. METHODS:The prescription variety and cost percentages of essential medicines in outpatient department in the two halves years of 2013 in our hospital(eye and ENT specialized hospitals)were compared;the medicines with forefront prescription kind percent-ages in eye and ENT departments were sorted and rankings in 4 quarters were compared. RESULTS:After the approval of the Na-tional Essential Medicine List(2012 edition),compared with the first half year of 2013,prescription variety and cost percentages of essential medicines in outpatient department in the second half year were significantly increased (P<0.01). Prescription variety and cost percentages of essential medicines in eye department in the second half year were significantly increased(P<0.01),in the top 20 prescription variety,totally 2 kinds were contained by the list 2012 edition and 3 were contained by the supplementary list of Shanghai(2012 edition). Compared with the first half year of 2013,prescription variety and cost percentages of essential medi-cines in ENT department in the second half year were significantly decreased(P<0.01),the cost percentage was significantly in-creased(P<0.01),in the top 20 prescription variety,totally 2 kinds were contained by the list 2012 edition and 3 were contained by the supplementary list of Shanghai (2012 edition). CONCLUSIONS:The prescription variety and cost percentages of essential medicines in our hospital show increase trend. Nevertheless,the non-essential medicines are still dominant and further improvement of essential medicines is still needed. Medicine variety and dosage forms of eye in ENT department are insufficient concluded in Es-sential Medicine List. Further adjustment of Essential Medicine List still needs more consideration for the medication characteristics in specialized hospital.

ObjectiveTo explore the effect of CQI on the teaching of physical diagnostics.MethodsThe theory and practice of CQI are discussed in accordance with specific conditions of the teaching of physical diagnostics.ResultsThe level of the teaching of physical diagnostics can be raised by applying CQI.ConclusionThere will be broad prospects in the application of CQI to quality teaching of physical diagnostics.

Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.
Aged ; Aging ; genetics ; metabolism ; pathology ; Amyotrophic Lateral Sclerosis ; genetics ; metabolism ; pathology ; Animals ; Animals, Genetically Modified ; Disease Models, Animal ; Drosophila melanogaster ; genetics ; metabolism ; Gene Expression ; Humans ; Microscopy, Electron, Scanning ; Motor Neurons ; metabolism ; pathology ; Mushroom Bodies ; metabolism ; pathology ; Mutant Proteins ; genetics ; metabolism ; Mutation ; Photoreceptor Cells, Invertebrate ; metabolism ; pathology ; Plasmids ; RNA-Binding Protein FUS ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism ; Retinal Degeneration ; pathology ; physiopathology ; Transfection