Objective To explore the influencing factors of Barrett's esophagus after endoscopic submucosal dissection(ESD)in patients with early esophageal cancer.Methods 110 patients with esophageal cancer who received ESD therapy in our hospital from January 2022 to March 2023 were divided into two groups according to whether they had Barrett's esophagus(n=20)and no Barrett's esophagus(n=90).The general clinical data,esophageal cancer related characteristics and ESD related treatment characteristics of the two groups were compared.Multivariate regression analysis were used to screen the risk factors of Barrett's esophagus in patients with esophageal cancer after ESD.Results The proportion of male,former drinking,former smoking,prevalence of peptic ulcer,multiple tumors,maximum diameter of tumors,the rate of postoperative lymph node metastasis,postoperative distant metastasis and the proportion of muscularis propria injury in patients with Barrett's esophagus were significantly higher(P＜0.05).Multivariate logistic regression analysis showed that alcohol drinking,smoking,peptic ulcer,postoperative lymph node metastasis,postoperative distant metastasis and injury of muscularis propria were the risk factors for Barrett's esophagus(P＜0.05).Conclusion Patients with a history of drinking,smoking,peptic ulcer,postoperative lymph node metastasis,postoperative distant metastasis and injury of muscularis propria are more likely to develop Barrett's esophagus after ESD.

Objective To explore the influencing factors of Barrett's esophagus after endoscopic submucosal dissection(ESD)in patients with early esophageal cancer.Methods 110 patients with esophageal cancer who received ESD therapy in our hospital from January 2022 to March 2023 were divided into two groups according to whether they had Barrett's esophagus(n=20)and no Barrett's esophagus(n=90).The general clinical data,esophageal cancer related characteristics and ESD related treatment characteristics of the two groups were compared.Multivariate regression analysis were used to screen the risk factors of Barrett's esophagus in patients with esophageal cancer after ESD.Results The proportion of male,former drinking,former smoking,prevalence of peptic ulcer,multiple tumors,maximum diameter of tumors,the rate of postoperative lymph node metastasis,postoperative distant metastasis and the proportion of muscularis propria injury in patients with Barrett's esophagus were significantly higher(P＜0.05).Multivariate logistic regression analysis showed that alcohol drinking,smoking,peptic ulcer,postoperative lymph node metastasis,postoperative distant metastasis and injury of muscularis propria were the risk factors for Barrett's esophagus(P＜0.05).Conclusion Patients with a history of drinking,smoking,peptic ulcer,postoperative lymph node metastasis,postoperative distant metastasis and injury of muscularis propria are more likely to develop Barrett's esophagus after ESD.

BACKGROUND:Biomimetic design of bioactive materials to restore,maintain or improve the function of tissue based on the understanding of anatomy on the function and structure of biological tissue is a research hotspot in the field of regenerative medicine at present. OBJECTIVE:To discuss the effect of mechanical properties,three-dimensional spatial structure,and biochemical activity of biomedical scaffolds on cell behavior and review the application of biomedical scaffolds in the field of tissue engineering. METHODS:The articles published in CNKI,Wanfang,Web of Science,and PubMed databases from January 2003 to April 2023 were searched by computer.The Chinese search terms were"extracellular matrix,tissue engineering,scaffolds,biomaterials,biomimetic structures,mechanical properties,three-dimensional structures,tendon-bone interface,osteochondral,neural conduits,artificial blood vessels".English search terms were"extracellular matrix,tissue engineering,scaffolds,biomimetic structures,biomaterials,tendon bone interfaces,osteochondral,neural conduits,artificial blood vessels". RESULTS AND CONCLUSION:Cells are in a complex and dynamic three-dimensional environment,so the extracellular matrix is the ultimate target of biomaterial simulation.The bionic structure of biomedical scaffolders needs to be similar to the real microenvironment,so that cells can stick to the wall,grow and migrate normally,and maintain their diverse physiological functions.Biomimetic design of extracellular matrix in terms of mechanical properties,three-dimensional spatial structure,and biochemical properties of biomedical scaffolds can play a decisive role in tissue repair,thus affecting the final result of tissue repair.Biomimetic biomedical scaffolds have been widely used in tendon-bone interface,bone cartilage interface,nerve,vascular regeneration,and other fields,providing a promising new idea in clinical practice.

Tumor-associated tertiary lymphoid structures(TLSs)are ectopic lymphoid formations within tumor tissue,with mainly B and T cell populations forming the organic aggregates.The presence of TLSs in tumors has been strongly associated with patient responsiveness to immunotherapy regimens and improving tumor prognosis.Researchers have been motivated to actively explore TLSs due to their bright clinical application prospects.Various studies have attempted to decipher TLSs regarding their formation mechanism,structural composition,induction generation,predictive markers,and clinical utilization.Meanwhile,the scientific approaches to qualitative and quantitative descriptions are crucial for TLS studies.In terms of detection,hematoxylin and eosin(H&E),multiplex immunohistochemistry(mIHC),multiplex immunofluorescence(mIF),and 12-chemokine gene signature have been the top approved methods.However,no standard methods exist for the quantitative analysis of TLSs,such as absolute TLS count,analysis of TLS constituent cells,structural features,TLS spatial location,density,and maturity.This study reviews the latest research progress on TLS detection and quantification,proposes new directions for TLS assessment,and addresses issues for the quantitative application of TLSs in the clinic.

OBJECTIVE To explore the value of providing pharmaceutical service related to risdiplam in direct-to-patient （DTP） pharmacies. METHODS The follow-up data of spinal muscular atrophy （SMA） patients who purchased and used risdiplam from Shangyao Yunjiankang Yiyao Pharmacy （Shanghai） Co.， Ltd. from May 2021 to January 2023 were collected. The medication information， therapeutic efficacy and the occurrence of adverse events were retrospectively analyzed. RESULTS A total of 42 prescriptions were checked by pharmacists in the DTP pharmacies， and 7 prescriptions were found to be unreasonable （16.7%， 7/42）， which were corrected after the timely intervention. During the follow-up management， pharmacists replied to 4 patients （9.5%， 4/42） regarding medication consultation about medication requirements and adverse events. Two patients with type Ⅰ SMA experienced adverse events： one of them presented with fever and the other presented with skin dryness with darkening. Both of them were grade Ⅰ toxic reactions and generally did not require clinical treatment. Considering that the patient sustained low-grade fever for a long time， the pharmacist suggested symptomatic treatment under the guidance of the doctor. CONCLUSIONS Pharmacists in DTP pharmacies conducting follow-up management of risdiplam use for rare disease SMA patients can help promote rational， standardized medication for patients.

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Objective:To investigate the levels of gross radioactivity in drinking water in Hangzhou city before and after Qiandao Lake as the water source to the main urban area of Hangzhou.Methods:Since 2012, water samples were collected from water source, factory water and peripheral water in rainy and dry seasons, respectively, to determine their gross α and β activity concentrations for comparison and analysis.Results:The gross radioactivity levels in drinking water in Hangzhou are lower than the limits specified in the national standard "Standards for drinking water quality" (GB 5749-2006), without statistically significant difference for these water sources between the rainy and dry season ( P>0.05). The gross α(0.008±0.000)and gross β(0.034±0.013)levels in Qiandao lake were both less than those in Qiantang river ( Z=-3.235, -4.058, P<0.05), with significant difference ( Z=-2.181, -4.577, P<0.05). There was no significant difference in gross α and gross β in factory water and peripheral water before and after the operation of Qiandao Lake water supply project ( P>0.05). Conclusions:The gross radioactivity in drinking water in downtown Hangzhou are low from 2012 to 2020. The gross radioactivity levels in Qiandao Lake are lower than in the lower reaches of Qiantang river and Dongtiao steam. No impact was generated on radioactivity levels in drinking water after Qiandao lake supplied water to Hangzhou.

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious global health threat.This raises an urgent need for the devel-opment of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14 (NSP14)carrying RNA cap guanine N7-methyltransferase and 3'-5'exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7％ of similarity with the one (PDB 5NFY) of acute respiratory syndrome (SARS) by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14 (PDB 5NFY) as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy (AG) was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model were-37.2711 ± 3.2160,-30.1746 ± 3.1914,-23.8953 ± 4.4800,and-34.1350 ± 4.3683 kcal/mol,respectively,while the calculated binding free energies were-60.2757 ± 4.7708,-30.9955 ± 2.9975,-46.3099 ± 3.5689,and-59.8104 ± 3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Objective:To evaluate the pathologic findings from biopsy samples to predict the status of nodal metastasis for patients with usual cervical adenocarcinoma.Methods:The 32-pair samples of cervical adenocarcinoma specimens (32 cervical biopsies and 32 hysterectomies with staging) from 2013 to 2019 were selected for retrospective study in Shanghai first Maternal and infant Health Care Hospital Affiliated to Tongji University. The correlation between histopathologic features including necrotic tumor debris (NTD), nuclear grade, mitotic count and pattern-based classification system and the status of lymph node metastasis was evaluated.Results:Tumor invasive patterns of cervical adenocarcinoma, as described previously, could be discerned in hysterectomy/staging specimens, but not in cervical biopsies. Because the biopsy tissues were small, only 14(14/32, 43.8%) cases could be classified according to pattern of invasion, and the concordance rate with resected specimens was 37.5%. NTD (9/19) and grade 3 nuclei (11/19) were positively correlated with invasive pattern C and nodal metastases ( P<0.05). Moreover, when NTD and (or) nuclear grade were evaluated at the same time, the sensitivity for type C infiltration was higher. Conclusions:Evaluation of NTD and nuclear grade in biopsies for cervical adenocarcinoma provides good predictive value for lymph node metastasis. It is helpful for patient stratification and management andto avoid unnecessary staging procedures. However, multicenter studies and prospective clinical trials are necessary to confirm the findings before clinical application can be considered.

Objective To investigate the diagnostic significance of the difference values between Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)in elderly patients with dementia.Methods 331 elderly patients with dementia were collected from outpatients in our hospital.There were 148 people with Alzheimer's disease (AD),87 cases with vascular dementia (VaD),44 cases with mixed dementia (MD),41 cases with frontotemporal dementia (FTD) and 11 cases with dementia with Lewy bodies (DLB).MMSE and MoCA were applied to test the cognitive impairment separately.Results The difference values between MMSE and MoCA was (3.3±1.7) points,(6.6±2.1) points,(6.6±2.1) points,(5.4±2.3) points,(6.1 ± 1.9) points in AD,VaD,MD,FTD and DLB group respectively,and there were statistical differences among the five groups (F=46.420,P=0.000).Statistical differences were found in the difference values between MMSE and MoCA between dementia patients with AD and non-AD (t=-13.429,P=0.000).According to receiver operating characteristic curve (ROC curve),the optimal cut off point of the difference values between MMSE and MoCA for differential diagnosis between AD and non-AD dementia was 5 points,with 79.8％ sensitivity and 78.4％ specificity,and area under the curve was 0.848 (95％CI:0.807-0.890).Conclusions The difference values between MMSE and MoCA may be one of parameters for differential diagnosis between AD and non-AD dementia.