[High expression of Circ-PALLD in heart failure is transcriptionally regulated by the transcription factor GATA4].

OBJECTIVE: To determine the changes in the expression of circular RNA Circ-PALLD in heart failure and explore the biogenesis of Circ-PALLD. METHODS: We analyzed second-generation sequencing results of human and murine heart failure samples to identify the candidate CircRNAs. Sanger generation sequencing was performed after PCR amplification, and the sequencing results were compared to determine the reverse splicing pattern of the corresponding CircRNAs. We further examined the expressions of CircRNAs and linear RNAs in 8 patients with heart failure admitted in our hospital, and RT-qPCR was performed to detect the expression levels of Circ-PALLD and PALLD in the failing myocardium. Bioinformatic analysis was performed to predict the transcription factors that may regulate PALLD. Small interfering RNAs (siRNAs) against GATA4 were used to determine the regulatory effect of the transcription factor GATA4 on PALLD. RESULTS: Sanger sequencing and sequence alignment verified the reverse splicing of Circ-VWA8, Circ-VMP1, Circ-PRDM5, Circ-PLCL2, Circ-PALLD, Circ-NFATC3, Circ-MLIP, Circ-FAM208A, Circ-ANKIB1, and Circ-AGTPBP1, demonstrated their loop-forming nature and determined the exon arrangement of reverse splicing. Semi-quantitative PCR results showed that the expression levels of CircPALLD, Circ-NFATC3 and Circ-AGTPBP1 were significantly increased while the expression level of linear PALLD was significantly decreased in the myocardial tissues of heart failure patients. Bioinformatic analysis suggested that the transcription of PALLD was regulated possibly by the transcription factor GATA4. RT-qPCR showed that the expression level of Circ-PALLD was significantly increased, while PALLD expression was significantly decreased in the failing myocardium, which was consistent with the results of semi-quantitative PCR. In primary mammary rat cardiomyocytes, GATA4 knockdown resulted in lowered expressions of both Circ-PALLD and PALLD. CONCLUSION: Circ-PALLD is highly expressed in heart failure and can be used as a novel molecular marker for chronic heart failure, and GATA4 may play important role in regulating its transcription. Circ-PALLD points a new direction for investigating the molecular mechanism of heart failure and may also serve as a potential therapeutic target for heart failure.

[Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study].

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

[Methodology and clinical use of superb microvascular imaging in assessing micro-circulation changes of fingertips in systemic sclerosis].

OBJECTIVE: To explore the feasibility of superb microvascular imaging (SMI) in evaluating microcirculation damage of the finger of systemic sclerosis (SSc), and determining the optimal scanning method by assessing the effect of scanning position (finger pulp or nail bed), plane (transverse or sagittal) and Doppler gain on the results. METHODS: In the study, 32 SSc patients and 32 non-SSc volunteers admitted to Peking University Third Hospital from February to October 2022 were included. The SMI image under different gain set (40 dB or 35 dB) of the third fingertip (sagittal scans or transverse scan of nail bed or pulp) of both hands were collected while vascular index (VI) was measured. RESULTS: Non-SSc volunteer presented abundant SMI signal distributed in the third fingertip. Arteriole of nail bed was observed on the dorsal side of the distal phalanx under SMI and gave off multiple vertical branches towards the nail. The arteriole of finger pulp ran parallel to the skin and gave off vertical branches towards the skin distributing subcutaneously as a network. In SSc group, the SMI signal in nail bed and finger pulp was reduced. The arteriole of nail bed and finger pulp was discontinuous and presented as sporadic dots and short rod-like color signal under SMI. The vascular index of the SSc patients was significantly lower than that of the non-SSc controls (P < 0.001). Among different positions and sections, the area under the receiver operating characteristic curve (AUC) of the sagittal plane of nail bed was the highest. Under low gain, the AUC of sagittal plane of nail bed was 0.871, the cut-off value was 5.4%, the sensitivity was 90.6%, and the specificity was 74.2%. Under high gain, the AUC was 0.893, the cut-off value was 14.0%, the sensitivity was 75.0%, and the specificity was 93.6%. Multivariate analysis showed that there was statistical significance on the diagnostic impact of the sagittal plane of nail bed (P < 0.005 for high gain condition; P < 0.05 for low gain condition). CONCLUSION: SMI can be used to evaluate the abnormal changes of vascular in patients with SSc. Using the sagittal scan of nail bed with high gain can evaluate the vascular loss of the fingertip in SSc patient accurately and specifically.

[Clinical effect of laparoscopy for the treatment of biliary stricture after biliary dilatation operation].

Objective: To investigate the safety and effect of laparoscopy for the treatment of biliary stricture after the biliary dilatation operation. Methods: The clinical data of 78 patients,including 27 males and 51 females aged (48.6±14.2)years(range:17 to 76 years),who presented biliary stricture after biliary dilatation operation from January 2017 to June 2021 in the Department of Minimally Invasive Hepatobiliary Surgery,Hunan Provincial People's Hospital,were retrospectively collected,with 38 cases in the laparoscopy group and 40 cases in the laparotomy group. Of the 78 patients,there were 67 cases of cholangiojejunostomy stricture and 11 cases of stricture of the high intrahepatic bile duct. Statistical methods such as t-test and χ2 test were carried out to compare perioperative clinical data and follow-up information between the two groups. Results: Less intraoperative blood loss((102.6±76.4)ml vs. (162.5±105.9) ml, t=-2.874,P=0.005),shorter postoperative stay length of stay((10.5±3.7)days vs. (14.5±6.4)days, t=-3.379,P=0.001) and shorter waiting time for postoperative anal exhaust((2.0±0.6)days vs. (2.5±0.9)days, t=-2.827,P=0.006) were found in the laparoscopy group than that in the laparotomy group,with statistically significant differences. While there was no statistically difference in the operative time((252.8±54.7)minutes vs. (257.4±68.6)minutes,t=-0.331,P=0.742). Postoperative review and follow-up did not show statistically significant differences between the two groups in the residual stone rate(5.3%(2/38) vs. 5.0%(2/40)) and the incidence of recurrent biliary stricture(5.3%(2/38) vs. 7.5%(3/40))(both P>0.05). Conclusion: Laparoscopy may be safe and effective in the treatment of biliary stricture after the biliary dilatation operation,with less trauma,faster recovery compared to laparotomy.

[Genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021].

Objective: To characterize the prevalence and genomic epidemiology of Vibrio parahaemolyticus from acute diarrheal patients in Shenzhen City from 2013 to 2021. Methods: Based on the Shenzhen Infectious Diarrhea Surveillance System, acute diarrheal patients were actively monitored in sentinel hospitals from 2013 to 2021. Whole-genome sequencing (WGS) of Vibrio parahaemolyticus isolates was performed, and the genomic population structure, serotypes, virulence genes and multilocus sequence typing were analyzed. Outbreak clusters from 2019 to 2021 were explored based on single-nucleotide polymorphism analysis. Results: A total of 48 623 acute diarrhea cases were monitored in 15 sentinel hospitals from 2013 to 2021, and 1 135 Vibrio parahaemolyticus strains were isolated, with a positive isolation rate of 2.3%. Qualified whole-genome sequencing data of 852 isolates were obtained. Eighty-nine serotypes, 21 known ST types and 5 new ST types were identified by sequence analysis, and 93.2% of strains were detected with toxin profile of tdh+trh-. 8 clonal groups (CGs) were captured, with CG3 as the absolute predominance, followed by CG189. The CG3 group was dominated by O3:K6 serotype and ST3 sequence type, while CG189 group was mainly O4:KUT, O4:K8 serotypes and ST189a and ST189 type. A total of 13 clusters were identified, containing 154 cases. About 30 outbreak clusters with 29 outbreak clusters caused by CG3 strains from 2019 to 2021. Conclusion: Vibrio parahaemolyticus is a major pathogen of acute infectious diarrhea in Shenzhen City, with diverse population structures. CG3 and CG189 have been prevalent and predominant in Shenzhen City for a long time. Scattered outbreaks and persistent sources of contamination ignored by traditional methods could be captured by WGS analysis. Tracing the source of epidemic clone groups and taking precise prevention and control measures are expected to significantly reduce the burden of diarrhea diseases caused by Vibrio parahaemolyticus infection in Shenzhen City.

[Solitary fibrous tumor in choroid: a clinicopathologic analysis of two cases].

Solitary fibrous tumor (SFT) is an uncommon spindle cell tumor that occurs mainly in the pleura, but also in other parts of the body. Intraocular SFT is very rare. This paper reports 2 cases of choroidal SFT which were diagnosed by clinical, imaging, histopathological and immunohistochemical staining. The patient remained asymptomatic with no sign of recurrence and metastasis after operation.

[Epidemiological characteristics of an epidemic of 2019-nCoV Omicron variant infection in Beijing].

Objective: To analyze the epidemiological characteristics and transmission chain of an epidemic of COVID-19 in Haidian district, Beijing. Methods: Descriptive epidemiological method was used to analyze the epidemiological characteristics of the epidemic, and field investigation and big data technology were used to analyze the transmission chain of the epidemic. Results: From April 27 to May 13, 2022, an epidemic of COVID-19 occurred in Haidian district. The strains isolated from the cases were identified by whole genome sequencing as Omicron variant (BA.2.2 evolutionary branch). A total of 38 infection cases were detected, including 34 confirmed cases and 4 asymptomatic cases. Most cases were mild ones (88.2%), no severe, critical or death cases occurred. The early clinical symptoms were mainly sore throat (50.0%) and cough (29.4%). The epidemic lasted for 17 days, resulting in 7 generations of the cases and involving 3 community transmissions, 2 working place transmissions and 8 family transmissions; the main infection routes were co-residence (47.6%) and co-space exposure (31.6%). The intergenerational interval M(Q1, Q3)was 3 (1, 6) days. The overall secondary attack rate was 1.5% (37/2 482), and the family secondary attack rate was 36.7% (18/49). Conclusions: The cases in this COVID-19 epidemic caused by Omicron variant had mild clinical symptoms, but the case clustering in families and communities was obvious, the transmission was rapid, and the risk for co-space exposure was high. It is necessary to use information technology to identify close contacts in the local population for the rapid and effective blocking of the epidemic spread.

Study for the binding affinity of thyroid hormone receptors based on machine learning algorithm.

Long-term exposure of exogenous compounds to thyroid hormone receptors (TRs) may lead to thyroid dysfunction. Quantitative structure-activity relationship (QSAR) is expected to predicting the binding affinity of compounds to TR. In this work, two comprehensive and large datasets for TRα and TRß were collected and investigated. Five machine learning models were established to predict the pIC50 of compounds. Meanwhile, the reliability of the models was ensured by a variety of evaluation parameters. The results showed that the support vector regression model exhibited the best robustness and external prediction ability (r2train = 0.77, r2test = 0.78 for TRα, r2train = 0.78, r2test = 0.80 for TRß). We have proposed an appropriate mechanism for explaining the TR binding affinity of a compound. The molecular volume, mass, and aromaticity affected the activity of TRα. Molecular weight, electrical properties and molecular hydrophilicity played a significant role in the binding affinity of compounds to TRß. We also characterized the application domain of the model. Finally, the obtained models were utilized to predict the TR binding affinities of 109 compounds from the list of endocrine disruptors. Therefore, this model is expected to be an effective tool for alerting the effects of exogenous compounds on the thyroid system.

Telomere length-related signature as a novel biomarker of prognosis and immune response in non-small cell lung cancer.

OBJECTIVE: Telomere length-related genes (TLRGs) play an important role in multiple tumors; however, there is a lack of systematic reporting about their relevance in non-small cell lung cancer (NSCLC). This study investigated the relation between TLRG gene expression and the immunotherapeutic response of patients with NSCLC. MATERIALS AND METHODS: Differentially expressed TLRGs in tumor tissues and normal tissues were screened using Gene Expression Omnibus (GEO) datasets. A univariate Cox regression analysis was performed to identify the optimal prognosis-related genes. A prognostic risk model was constructed by using least absolute shrinkage, selection operator, and multivariate Cox regression analysis results. The model was then evaluated by a Kaplan-Meier analysis, functional enrichment annotation, and a receiver operating characteristic curve analysis; after which, it was validated in the TCGA dataset. The model was used to predict immunotherapeutic response and drug sensitivity. RESULTS: An 18-gene prognostic signature was developed and used to stratify NSCLC patients into a low- or high-risk group in GEO cohorts. Patients in the low-risk group had better survival possibilities than those in the high-risk group, and showed significantly higher overall survival times in the TCGA cohort. The risk score was identified as an independent prognostic factor, when compared with other clinical factors. ssGSEA scores showed that the risk model was mainly linked to cancer- and immune-related pathways. Importantly, the candidate risk model was linked to tumor immunity and predicted a patient's response to PDL-1 blockade immune therapy. Several potential drugs that might target this model were identified. CONCLUSIONS: This study provides broad molecular signatures that can be used in further functional and therapeutic studies of the telomere system, and also represents an integrated approach for characterizing key protein complexes when creating a prognosis and identifying new targets for cancer immunotherapy.

[Efficacy and survival outcomes of dose-dense carboplatin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer].

Objective: To evaluate the efficacy and survival outcomes of dose-dense (biweekly) carboplatin plus paclitaxel (PC) as neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC), and to explore an optimal neoadjuvant chemotherapy regimen for TNBC. Methods: Patients diagnosed as TNBC(cT1-4N0-3M0) in Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Between January 2008 and September 2018 who received dose-dense PC and standard 3-weekly PC as NAC were 1∶1 matched using propensity score matching (PSM) to compare the efficacy, safety and survival outcomes. Results: One hundred of TNBC patients were enrolled (50 patients were divided in dose-dense group, 50 patients in standard group). The objective response rate (ORR) of dose-dense group and standard group were both 90.0% (45/50). The grade 3-4 neutropenia in dose-dense group was less than that of standard group (32.7% vs. 68.0%, P=0.001), while the rate of ALT/AST elevation in dose-dense group was higher than that of standard group (57.1% vs. 32.0%, P=0.012). The pathological complete response (pCR) rates were 34.0% (17/50) in dose-dense group and 38.0% (19/50) in standard group, without statistically significance (P=0.677). The median follow-up time was 55 months (3-150 months). The 5-year recurrence-free survival (RFS) in dose-dense group and standard group were 83.5% and 75.2%, respectively the 5-year overall survival (OS) in dose-dense and standard group were 87.9% and 84.5% the difference were not statistically significant (P=0.322 and 0.647, respectively). Patients with residual disease (tumor size≥1 cm or lymph node positive) had poor prognosis, the 5-year RFS and OS were 59.3% and 68.5%, respectively. Conclusions: Dose-dense PC has similar efficacy with standard 3-weekly PC and has a good safety profile. Since dose-dense regimen can shorten the duration of therapy, it can be an alternative in TNBC.

[The clinicopathologic features and differential diagnosis of ocular Kimura disease and epithelioid hemangioma].

Objective: To investigate the clinicopathologic features and differential diagnosis of ocular Kimura disease (KD) and epithelioid hemangioma. Methods: It was a retrospective case series study. The data of 10 patients with ocular KD and 3 patients with ocular epithelioid hemangioma from the Pathology Department of Eye & ENT Hospital of Fudan University from January 2010 to December 2019 were retrospectively analyzed, including clinical manifestations, morphology and immunophenotypes. Results: Among patients with ocular KD, there were 9 males and 1 female with an age from 7 to 75 years (mean, 30 years). There were 6 unilateral cases and 4 bilateral cases. The disease mainly involved the orbit in 3 patients, the lacrimal gland in 5 patients and the eyelid in 2 patients. The ophthalmic presentation included a palpable periorbital or eyelid mass with eyelid swelling and ptosis, proptosis and displacement of the eyeball, and ocular dysmotility. Three patients had a history of lymphadenopathy. The disease course ranged from 6 months to 7 years (mean, 34 months). All the patients had elevated peripheral blood eosinophilia. Three patients of ocular epithelioid hemangioma were all males with age from 25 to 60 years old. They were all unilateral cases with 1 right eye and 2 left eyes. The disease respectively involved eyelid and orbit, the eyebrow skin and the inner canthus skin. They presented with eyelid swelling, orbital mass or subcutaneous nodule for 5 months to 2 years. All patients (11 eyes) with KD underwent incisional or excisional biopsy. The histopathology revealed follicular hyperplasia of lymphoid tissue with active germinal centers in orbital fibroadipose tissue. There were massive interfollicular eosinophils with eosinophilic microabscesses. Some swelling endothelial cells of proliferating vessels were seen. All the 3 patients (3 eyes) with ocular epithelioid hemangioma underwent excision of the lesions. Histopathological examination showed proliferation of small and medium blood vessels. The vessels were lined by endothelial cells with abundant eosinophilic cytoplasm which protruded into the lumen. The endothelial cells were positive for CD31, factor Ⅷ-related antigen and E26 transformation-specific related gene immunohistochemically. There was a moderate amount of lymphocytes, plasma cells and eosinophils surrounding blood vessels without eosinophilic microabscess. Conclusions: Both ocular KD and epithelioid hemangioma are more commonly seen in males and share the common histopathological features of vascular proliferation, swelling endothelial cells and eosinophilic infiltration. KD is an allergic benign lymphoid tissue proliferation characteristic of massive eosinophilic infiltration, whereas epithelioid hemangioma is a benign neoplasm of blood vessels with plump and epithelioid endothelial cells. (Chin J Ophthalmol, 2021, 57: 689-695).

[Analysis on adult health life expectancy in Shanghai].

Objective: To investigate health status and calculate health life expectancy (HE) of residents in Shanghai, analyze health related factors and provided foundation of health policy. Methods: A multi-stage stratified random sampling was used to obtain self-reported health survey in Shanghai. WHO questionnaire was used to evaluate the health quality of life which was designed for the world health survey, Sullivan's method was used to calculate HE. Results: The self-assessment disability measure for adults over 18 years old in Shanghai was 0.25, higher for women (0.28) than for men (0.23). LE was 65.76 years for adults over 18 years old, higher for women (68.22) than for men (63.39). HE for adults over 18 years old was 47.99 years old, higher for men (49.05) than women (47.14). HE's proportion in LE gradually decreases with age. It accounts for 72.97% in the 18 years old and 39.00% in the 85 years old. Conclusions: The health of adult male in Shanghai is higher than that of female, and the proportion of HE loss of elderly is higher than young people. It is necessary to focus on the aging problem and strengthen the long-term care and health support system for the elderly. Improve the prevention and control of major diseases such as chronic diseases,which affect the quality of life expectancy seriously. Promotes the health level and quality of life in Shanghai.

[Analysis on the difference between life expectancy and healthy life expectancy in Shanghai].

Objective: To analyze the difference of life expectancy and healthy life expectancy among Shanghai residents of different gender and age groups. Methods: Compare the trends of life expectancy among Shanghai and other longevity countries/regions. With the disability weights of GBD, Sullivan method was applied to calculate the healthy life expectancy in Shanghai and analyze the loss of healthy life years among the population of different age groups and genders. Results: In the past 40 years, life expectancy had increased by 10.86 years in Shanghai. In 2016, the life expectancy of Shanghai residents was 83.18 years old, and 80.83 years old for males and 85.61 years old for females. The healthy life expectancy of Shanghai residents was 69.46 years, and 68.68 years for males and 70.23 years old for females. The gap with life expectancy was 13.72 years old, 12.15 years old and 15.38 years old, respectively. They account for 16.49%, 15.02% and 17.97% of life expectancy, respectively. The healthy life expectancy of women in all age groups is higher than that of men with the average gap of 1.76 years. The difference between the two is as small as 1.36 years at 20-24 years old, and as large as 2.24 years at 70-74 years old. The loss rate of healthy life expectancy increases with age, with women higher than men before age 65 and vice versa after age 65 years old. Conclusions: The life expectancy in Shanghai has reached the world leading level, but the healthy life loss is still large. It is necessary to further improve the life quality with the reducing mortality rate, especially for women and men over 65 years old.

[Analysis of the effect of ipsilateral supraclavicular lymph node metastasis on the prognosis of N3 breast cancer].

Objective: The 6th edition American Joint Committee on Cancer (AJCC) staging system for breast cancer classifies ipsilateral supraclavicular lymph node metastasis (ISLM) downing stage from M1 to N3, suggesting more patients might receive radical treatment. The aim of this study was to analyze the effect of ISLM on the prognosis of N3 breast cancer and verify the rationality of modified staging. Methods: A total of 321 breast cancer patients with N3 according to the 6th edition AJCC staging system were retrospectively analyzed. Propensity Score Matching (PSM) was used to pair the different subgroups of N3. The primary end point was disease-free survival (DFS), the secondary end point was overall survival (OS). Kaplan-Meier method was used to calculate the DFS and OS. The differences between two groups were analyzed by the Log-rank test. Results: After PSM pairing twice, 78 patients with none-ISLM and 78 patients with ISLM were enrolled in the first group; 51 patients with none-ISLM was compared patients with isolated ISLM in the second group. The results of the two groups showed that patients with none-ISLM have a prolonged DFS (the first group: 58.9 months vs 32.1 months, P=0.101; the second group: 59.0 months vs 44.0 months, P=0.533), while the OS was opposite (the first group: 87.4 months vs 140.4 months, P=0.289; the second group: 87.4 months vs 137.1 months, P=0.289). Conclusions: The prognosis of breast cancer patients with ISLM is similar to that of patients with none-ISLM in stage N3. It is reasonable to include ISLM in N3 in the 6th edition AJCC staging system. Yet, prospective studies with larger sample size are needed to further confirmation.

The important role of TFEB in autophagy-lysosomal pathway and autophagy-related diseases: a systematic review.

Autophagy is a main metabolic process in which eukaryotic cells use lysosomes to eliminate abnormal proteins and damaged organelles to maintain cell homeostasis. Studies have revealed that neurodegenerative diseases, tumor, hepatic diseases, etc. are related to abnormal autophagy processes in recent years. Recent studies have shown that TFEB is a major transcription regulator of autophagy-lysosomal pathway (ALP) transcriptional regulation, which positively regulates the expression of autophagy and lysosomal biogenesis-related genes, thereby promoting autophagosome formation, autophagosome-lysosome fusion, and degradation of autophagy substrates. It has also been found that TFEB promotes clearance of intracellular substrates through lysosomal exocytosis. Therefore, the study of biological functions and related regulatory mechanisms of TFEB will provide important clues and theoretical basis for further explaining its physiological pathogenesis and the treatment of related diseases.

Treatment persistence in paediatric and adolescent patients with psoriasis followed into young adulthood. From topical to systemic treatment: a prospective, longitudinal, observational cohort study of 448 patients.

BACKGROUND: Although solely topical treatment often suffices, patients with psoriasis may require more intensive treatment (phototherapy and/or systemic treatments) to control their disease. However, in paediatric, adolescent and young adult patients, little is known about persistence of topical treatment and time until switch to systemic treatment. OBJECTIVES: To determine the median time from psoriasis onset until (i) discontinuation of solely topical agents and (ii) switch to systemic treatment, and to identify patient characteristics associated with switching to systemic treatments. METHODS: Data were extracted from the Child-CAPTURE registry, a prospective, observational cohort of patients with paediatric-onset psoriasis followed into young adulthood from 2008 to 2018. Data prior to inclusion in the registry were collected retrospectively. Median times were determined through Kaplan-Meier survival analyses. Cox regression analysis was used to identify patient characteristics associated with switch to systemic treatment. RESULTS: Of 448 patients, 62·3% stayed on solely topical treatment until data lock; 14·3% switched from topicals to phototherapy, but not to systemic treatment; and 23·4% switched to systemic treatment. The median time from psoriasis onset until discontinuation of solely topical treatment was 7·3 years, and until switch to systemics was 10·8 years. Higher Psoriasis Area and Severity Index and (Children's) Dermatology Life Quality Index > 5 were independently associated with switching to systemic treatment. CONCLUSIONS: In a population of paediatric and adolescent patients with mild-to-severe psoriasis, one-third needed more intensive treatment than solely topical therapy to control their disease. We consider the median time until switching to systemics to be long.

[Application of Chen's pancreaticojejunostomy technique in laparoscopic pancreaticoduodenectomy (116 cases report)].

Objective: To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen's pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD). Methods: Clinical data of 116 consecutive patients who underwent LPD using Chen's pancreaticojejunostomy technique in Hunan Provincial People's Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen's pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed. Results: All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes). The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2%(13/116) of cases had postoperative pancreatic fistula (POPF), including 10.3% (12/116) of biochemical fistula and 0.9%(1/116) of grade B POPF, no grade C POPF occurred; 10.3%(12/116) had gastrojejunal anastomotic bleeding; 3.4%(4/116) had hepaticojejunal anastomotic fistula; 3.4%(4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1%(14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7%(2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery. Conclusions: Chen's pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.