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Liu-Cheng Li,1,* Yong-Yue Han,2,* Zhi-Hui Zhang,3,4 Wen-Cheng Zhou,5,6 Hong-Mei Fang,1 Jiao Qu,7 Lian-Di Kan1 1Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People’s Republic of China; 2School of Pharmacy, Dalian Medical University, Dalian 116044, People’s Republic of China; 3Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, People’s Republic of China; 4Shanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai 200082, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou 310006, People’s Republic of China; 6Department of Pharmacy, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou 310006, People’s Republic of China; 7State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian-Di KanDepartment of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People’s Republic of ChinaTel +86-571-86006803Email 3198004@zju.edu.cnJiao QuState Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing 210023, People’s Republic of ChinaTel +86-25-89687620Email qujiao19920819@163.comAbstract: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death across the globe. Its repeated exacerbation will seriously worsen the quality of life, aggravate the patients’ symptoms, and bring a heavy burden on the patients and the society. Understanding the current status of drug therapy and the role of pharmaceutical care is essential for the management of COPD. In addition to the drugs already on the market, recent clinical trials also show that emerging novel drugs for treating COPD are being developed to prevent the symptoms, reduce the frequency of acute exacerbation, and improve the quality of life. Recent progress in new drug research should lead to novel treatment options for COPD patients in future clinical practice. The pharmaceutical care has shown significantly favourable impacts on addressing drug-related problems, supporting its vital role in the management of COPD, especially when there are a wide range of therapeutic agents. This review not only provides an overview of current treatment strategies but also further underlines the importance of new drug development and pharmaceutical care for patients with COPD.Keywords: chronic obstructive pulmonary disease, drugs, clinical trial, complications, pharmaceutical care

Background: Glucose-regulated protein 78 (GRP78), as a chaperone protein, can protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or cell cycle arrest., Object: This study was performed to demonstrate the molecular mechanism by which DPT attenuates osteosarcoma progression through GRP78., Methods: Natural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)- Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'- deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma cells treated with DPT. We constructed an in vivo mouse model of DPT drug therapy and carried out immunohistochemical detection of xenografts. The treated osteosarcoma cells were analyzed using bioinformatics and electron microscopy. The data were analyzed finally., Results: DPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated by the overexpression of GRP78, characterized by the inactivation of the caspase cascade. The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagyassociated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR) axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and blocked the apoptotic cascade., Conclusion: Combination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Lung adenocarcinoma (LUAD) is one of the respiratory diseases with high mortality and incidence. As an important angiogenic factor, (Endothelial cell-specific molecule 1) ESM1 plays an important role in the occurrence and development of LUAD. However, the role and molecular mechanism of ESM1 on LUAD metabolic reprogramming and angiogenesis remain unclear., Methods: We used multiple databases to analyze the prognostic significance and potential function of ESM1 in patients with LUAD. The expression of ESM1 in LUAD cells was down-regulated/overexpressed by RNA interference, and the effects of ESM1 on the proliferation, migration, lipid metabolism and angiogenesis of LUAD cells in vitro and in vivo were analyzed using MTT, EdU, wound healing, oil red O, tubule formation, xenograft tumor model and chicken embryo allantoic model., Results: ESM1 is closely associated with poor prognosis in LUAD patients. ESM1 promotes LUAD proliferation, migration, fatty acid synthesis and angiogenesis. It also accelerates the proliferation, migration, lipid synthesis and tubule formation of endothelial cells in the tumor microenvironment in the form of secreted protein. Mechanically, ESM1 can promote the activation of AKT signaling pathway and up-regulate the expression of SCD1 and FASN., Conclusion: Our results suggest that ESM1 promotes the proliferation, migration, lipid reprogramming, and angiogenesis of LUAD cells by activating the AKT signaling pathway, suggesting that ESM1 may be a potential therapeutic target and prognostic marker in LUAD patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Pancreatic cancer (PC) has a really poor prognosis, and we urgently need to delve deeper into its molecular mechanisms. In this study, we found that KRT19 expression was significantly increased in PC tissues and cell lines and it was linked to unfavorable outcomes for patients. Overexpression of KRT19 boosted the proliferation, migration, and invasion of PC cells. Additionally, miR-374b-5p targets KRT19, inhibiting the activation of the Wnt/β-catenin pathway (WBC), which in turn suppresses epithelial-to-mesenchymal transition (EMT) and the progression of PC. Further experiments showed that under hypoxic conditions, HIF1α was positively correlated with KRT19, promoting its expression. The loss of miR-642a-5p and the upregulation of KRT19 induced by hypoxia can significantly favor PC progression. Plus, the increased expression of KRT19 might act as a predictive marker and potential target for PC treatment., Competing Interests: The authors declare no competing financial interests., (© 2024 The Author(s).)

Objective: To investigate whether heavy metal cadmium acts as a risk factor for temporomandibular joint disorder disease and to study its pathogenic mechanism., Methods: A total of 57 rats were allocated into 6 distinct groups, distinguished by 2 interventions: occlusal elevation and cadmium water gavage. These groups included a blank control group, occlusal elevation group, occlusal elevation + 0.42 mg/mL cadmium water gavage group, occlusal elevation + 4.2 mg/mL cadmium water gavage group, no occlusal elevation + 0.42 mg/mL cadmium water gavage group, and no occlusal elevation + 4.2 mg/mL cadmium water gavage group. The impact of cadmium exposure on cartilage oxidative stress was evaluated through the assessment of SOD, CAT, GST, and GSH-Px enzyme activities. In addition, the influence of cadmium exposure on alterations in the extracellular matrix and inflammatory mediators was examined by analyzing the expression levels of type II collagen, protein aggregation polysaccharide, glycosaminoglycan, IL1β, IL-6, and TNF-α. Histologic examination of the condylar process cartilage of rats in the occlusal elevation + cadmium water gavage group was conducted to ascertain the occurrence of osteoarthritis., Results: The variance in the expression levels of inflammatory factors did not demonstrate statistical significance between the occlusal elevation group and the blank control group; however, statistical significance was observed between the occlusal elevation + cadmium water gavage group and both the control and occlusal elevation groups., Conclusion: The severity of inflammation and condylar lesions correlates directly with the concentration of cadmium., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Background: Oral immunotherapy (OIT) is a promising allergen-specific approach in the management of food allergy; however, studies on OIT for allergic rhinitis (AR) have rarely been reported. The purpose of this study is to evaluate the efficacy and safety of OIT using enteric-coated capsules for AR induced by house dust mites., Methods: A total of 49 patients with AR were enrolled, including 25 who received subcutaneous immunotherapy (SCIT) and 24 who received OIT. The clinical efficacy and safety in both groups were evaluated., Results: After 1 year of treatment, both SCIT and OIT demonstrated significant therapeutic effects. OIT was found to be more effective than SCIT in reducing the total AR symptom score and improving the results of nasal provocation tests. Local and systemic adverse reactions were observed in the SCIT group, while none were reported in the OIT group., Conclusion: OIT is an effective and safe treatment for mite-induced AR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Zhang, Xie, Zhou, Chen, Wang, Zhu, Wen and Cheng.)

Objective: The five-needle pancreato-intestinal anastomosis method is used in laparoscopic pancreaticoduodenectomy (LPD). The aim of this study was to explore the clinical efficacy and adverse reactions of this new surgical method and to provide a scientific reference for promoting this new surgical method in the future., Methods: A single-centre observational study was conducted to evaluate the safety and practicality of the five-needle method for pancreatojejunostomy in LPD surgeries. The clinical data of 78 patients who were diagnosed with periampullary malignancies and underwent LPD were collected from the 1 st of August 2020 to the 31 st of June 2023 at Lanzhou University First Hospital. Forty-three patients were treated with the 'Five-Needle' method (test groups), and 35 patients were treated with the 'Duct-to-Mucosa' method (control group) for pancreatojejunostomy. These two methods are the most commonly used and highly preferred pancreatointestinal anastomosis methods worldwide. The primary outcome was pancreatic fistula, and the incidence of which was compared between the two groups., Results: The incidence of pancreatic fistula in the five-needle method group and the duct-to-mucosa method group was not significantly different (25.6% vs. 28.6%, p=0.767). Additionally, there were no significant differences between the two groups in terms of intraoperative blood loss (Z=-1.330, p=0.183), postoperative haemorrhage rates (p=0.998), length of postoperative hospital stay (Z=-0.714, p=0.475), bile leakage rate (p=0.745), or perioperative mortality rate (p=0.999). However, the operative time in the 'Five-Needle' method group was significantly shorter than that in the 'Duct-to-Mucosa' method group (270 ± 170 mins vs. 300 ± 210 mins, Z=-2.336, p=0.019). Further analysis revealed that in patients with pancreatic ducts smaller than 3 mm, the incidence of pancreatic fistula was lower for the 'Five-Needle' method than for the 'Duct-to-Mucosa' method (12.5% vs. 53.8%, p=0.007)., Conclusion: The five-needle method is safe and efficient for pancreatojejunostomy in LPD, and is particularly suitable for anastomosis in nondilated pancreatic ducts. It is a promising, valuable, and recommendable surgical method worthy of wider adoption., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Zhang, Xu and Zhou.)

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignant tumor of the biliary tract that is prone to recurrence and metastasis and is characterized by poor sensitivity to chemotherapy and overall prognosis. For these reasons, there is an urgent need to understand its pathological mechanisms and develop effective treatments. To address this challenge, the establishment of suitable preclinical models is critical., Methods: Fresh ICC tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, and short tandem repeat (STR) analysis. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-fluorouracil (5-FU) were evaluated by CCK-8 assay. Subcutaneous injection of 1 × 10 6 cells to three BALB/c nude mice was conducted for xenograft studies. The hematoxylin and eosin (H&E) staining was used to detect the pathological status of the cell line. The expression of biomarkers CK7, CK19, Ki-67, E-cadherin and vimentin was determined by immunocytochemistry assay., Results: A new ICC cell line named ICC-X2 was successfully established. Like ICC-X3 established using the same patient's metastatic tumor, the cell line has been continuously cultured in vitro for more than a year and has been passaged more than 100 times. ICC-X2 retained the typical biliary epithelial morphology. The population doubling time of ICC-X2 is 48 h. The cells demonstrated an abnormal nearly tetraploid karyotype. The STR analysis confirmed that ICC-X2 was highly consistent with the primary tumor tissue and not cross-contaminated by existing cell lines. ICC-X2 cells positively expressed CK7, CK19, E-cadherin, and vimentin, and the positive expression of Ki-67 in ICC-X2 cells was 40%. The ICC-X2 cells exhibited a strong clonogenic ability. The drug sensitivity test indicated that ICC-X2 was sensitive to oxaliplatin and paclitaxel, but naturally resistant to gemcitabine and 5-FU. ICC-X2 was rapidly able to form transplanted tumors in vivo after subcutaneous inoculation in nude mice., Conclusions: ICC-X2 is an excellent experimental model that can be used for studying the occurrence, development, and metastasis of ICC and investigating the mechanism of tumor drug resistance., Competing Interests: The authors declare no competing interests., (Copyright 2024, Xu et al.)

Background: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated., Methods: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking., Results: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis., Conclusion: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1., (© 2024. The Author(s).)

Ampelopsis grossedentata is a valuable medicinal and edible plant, which is often used as a traditional tea by the Tujia people in China. A. grossedentata has numerous biological activities and is now widely used in the pharmaceutical and food industries. In this study, two new flavonoids ( 1 - 2 ) and seventeen known compounds ( 3 - 19 ) were isolated and identified from the dried stems and leaves of A. grossedentata . These isolated compounds were characterized by various spectroscopic data including mass spectrometry and nuclear magnetic resonance spectroscopy. All isolates were assessed for their α-glucosidase inhibitory, antioxidant, and hepatoprotective activities, and their structure-activity relationships were further discussed. The results indicated that compound 1 exhibited effective inhibitory activity against α-glucosidase, with an IC 50 value of 0.21 μM. In addition, compounds 1 - 2 demonstrated not only potent antioxidant activities but also superior hepatoprotective properties. The findings of this study could serve as a reference for the development of A. grossedentata-derived products or drugs aimed at realizing their antidiabetic, antioxidant, and hepatoprotective functions.

Angiopoietin4(ANGPT4) which plays a significant role in endothelial cell proliferation, survival, angiogenesis and expansion in tumors and other pathological states is a significant regulator of tumor angiogenesis. ANGPT4 expression is enhanced in many cancer cells. For example, the overexpression of ANGPT4 promotes the formation, development and progress of lung adenocarcinoma, glioblastoma and ovarian cancer. Related studies show that ANGPT4 encourages the proliferation, survival and invasion of tumor cells, while promoting the expansion of the tumor vascular system and affecting the tumor immune microenvironment. ANGPT4 can also promote carcinogenesis by affecting the ERK1/2, PI3K/AKT and other signal pathways downstream of tyrosine kinase with immunoglobulin-like and EGF-like domains 2(TIE2) and TIE2. Therefore, ANGPT4 may be a potential and significant biomarker for predicting malignant tumor progression and adverse outcomes. In addition, inhibition of ANGPT4 may be a meaningful cancer treatment. This paper reviews the latest research results of ANGPT4 in preclinical research, and emphasizes its role in carcinogenesis. Additional research on the carcinogenic function of ANGPT4 could provide new insights into cancer biology and novel methods for cancer diagnosis and treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: An in-depth study of the pathogenesis and biological characteristics of ampullary carcinoma is necessary to identify appropriate treatment strategies. To date, only eight ampullary cancer cell lines have been reported, and a mixed-type ampullary carcinoma cell line has not yet been reported., Aim: To establish a stable mixed-type ampullary carcinoma cell line originating from Chinese., Methods: Fresh ampullary cancer tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, short tandem repeat (STR) analysis and transmission electron microscopy. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-FU were evaluated by cell counting kit-8 assay. Subcutaneous injection 1 × 10 6 cells to three BALB/c nude mice for xenograft studies. The hematoxylin-eosin staining was used to detect the pathological status of the cell line. The expression of biomarkers cytokeratin 7 (CK7), cytokeratin 20 (CK20), cytokeratin low molecular weight (CKL), Ki67 and carcinoembryonic antigen (CEA) were determined by immunocytochemistry assay., Results: DPC-X1 was continuously cultivated for over a year and stably passaged for more than 80 generations; its population doubling time was 48 h. STR analysis demonstrated that the characteristics of DPC-X1 were highly consistent with those of the patient's primary tumor. Furthermore, karyotype analysis revealed its abnormal sub-tetraploid karyotype. DPC-X1 could efficiently form organoids in suspension culture. Under the transmission electron microscope, microvilli and pseudopods were observed on the cell surface, and desmosomes were visible between the cells. DPC-X1 cells inoculated into BALB/C nude mice quickly formed transplanted tumors, with a tumor formation rate of 100%. Their pathological characteristics were similar to those of the primary tumor. Moreover, DPC-X1 was sensitive to oxaliplatin and paclitaxel and resistant to gemcitabine and 5-FU. Immunohistochemistry showed that the DPC-X1 cells were strongly positive for CK7, CK20, and CKL; the Ki67 was 50%, and CEA was focally expressed., Conclusion: Here, we have constructed a mixed-type ampullary carcinoma cell line that can be used as an effective model for studying the pathogenesis of ampullary carcinoma and drug development., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The occlusal force of the teeth in the dental arch and the remaining adjacent natural teeth will change after implant restoration with a free-end missing tooth. This study intends to use the T-SCAN III scanner to collect dynamic quantitative data before and after the restoration of free-end implants and to explore the application of the T-SCAN III in redistributing the occlusal force of free-end implants. Methods: In this study, 24 patients with free-end implant restoration were selected, and their occlusion was tested before, immediately after, and 3 months after implant restoration. Results: In all 24 cases, the bite force of the first natural tooth adjacent to the implanted tooth after restoration changed from 19.12% ± 9.48%-12.93% ± 11.47% ( p < 0.01). For additional data analysis, all cases were further subdivided by single implant and fixed bridge restorations. In 17 cases, there was a successful follow-up after 3 months. The percentage of the total bite force of dental arch with implant increased from 41.92% ± 10.78%-53.06% ± 10.71% ( p < 0.01). Discussion: This study shows that the free-end implant restoration protects the remaining natural teeth, and the patient's missing dental arch bite force improves within 3 months of implant restoration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Lai, Cheong, Zhou, Xu, Li and Shen.)

Objective: To investigate the clinical effects of free descending branch tissue flap of lateral circumflex femoral artery in repairing Wagner grade 3 or 4 diabetic foot wounds. Methods: A retrospective observational study was conducted. From October 2019 to January 2022, 12 patients (10 males and 2 females, aged 38-66 years, with an average of 52 years) with diabetic foot wounds who met the inclusion criteria were admitted to the First People's Hospital of Yulin, of whom 5 cases being Wagner grade 3 and 7 cases being Wagner grade 4. Wound debridement and vacuum sealing drainage were performed to control infection, and the wound area after debridement was between 13 cm×6 cm and 28 cm×11 cm. The wounds were repaired with free descending branch tissue flaps of lateral circumflex femoral artery. Among them, the wounds of 4 cases were repaired with single flap of musculocutaneous branch or intermuscular branch of descending branch tissue flap of lateral circumflex femoral artery, 1 case with lobulated flap, 1 case with bilateral tandem flap, and 6 cases with chimeric lateral femoral muscle flap. The area of resected tissue flap was 9 cm×7 cm to 21 cm×10 cm; end-to-end anastomosis was selected between vessels in the donor sites and the recipient sites, and pressurized treatment should be performed if necessary. The donor site wounds of 10 patients were treated with cosmetic tension-relieving suture, and the donor site wounds of 2 patients were repaired with split-thickness skin graft from head. After operation, the condition of wound repair was recorded. After wound healing, the level of 2-hour postprandial blood glucose of patients was measured. During follow-up, the wound healing of the recipient site and scar formation of the donor site were observed. Before and 6 months after operation, computer tomography angiography was used to detect and compare the blood perfusion of the affected limb. At the last follow-up, the walking ability of the patients was recorded. Results: The wounds of 9 patients healed well after operation; the flaps in the recipient site of 2 patients were infected on postoperative day 5 after surgery and were repaired by suturing in stage Ⅱ after open drainage and inflammation control; the distal end of the grafted tandem flap in 1 patient gradually developed purple necrosis on postoperative day 4 and was repaired with a skin graft after debridement. After wound healing, the 2-hour postprandial blood glucose value of all patients was controlled in the range of 8-12 mmol/L. During Follow-up of 6 months to 1 year, 3 patients had partial ulceration in the plantar compression area, which healed after decompression combined with dressing change or flap repair, while the other 9 patients had no ulceration in the recipient area; the appearance of the affected foot was plump after wound healing, the transplanted flaps had good blood supply and good fit with the surrounding tissue, and were wear-resistant, but insensitive. During follow-up, only linear scar remained in the donor area of direct suture in 10 cases, and the skin grafts in the donor area were completely survived in 2 cases. Compared with the patency of the main blood vessels of the ankle joint segment of the affected limb before operation, the vascular network of the flap transplantation area in the affected foot was formed 6 months after operation. At the last follow-up, 8 patients could walk independently, and 4 patients could walk with crutches. Conclusions: The free descending branch tissue flap of lateral circumflex femoral artery is effective in repairing Wagner grade 3 or 4 diabetic foot wounds, which can shorten the course of disease and improve local blood flow.

It is unclear whether hepatic artery infusion chemotherapy (HAIC) or transcatheter arterial chemoembolization (TACE) is more efficient in the combination therapy of hepatocellular carcinoma (HCC). Head-to-head comparisons among HAIC-related therapies are lacking. For this network meta-analysis, PubMed, EMBASE and Cochrane Library databases were searched up to April 1, 2022. Randomized controlled trials (RCTs) were eligible if they evaluated the use or prolongation of TACE or HAIC in patients with advanced HCC and reported or collected survival data. A network meta-analysis was performed to synthesize data and make direct and indirect comparisons between treatments. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to explore the efficacy of various treatment options on overall survival (OS), odds ratios (ORs) with 95% CI were used for overall response rate (ORR), whereas risk ratios (RRs) with 95% CI were used for serious adverse events (SAEs). The analysis of 7 trials including a total of 1,073 patients found that sorafenib with HAIC-oxaliplatin improved survival (HR=0.33, 95% CI: 0.25-0.44); the ORR was also improved in patients treated with sorafenib plus HAIC-oxaliplatin and sorafenib plus PF-HAIC (OR=22.18, 95% CI: 10.69-52.56; and OR=2.72, 95% CI: 1.43-5.36, respectively). The incidence of liver injury was elevated in patients treated with sorafenib plus TACE (OR=5.93, 95% CI: 2.70-15.41). However, no differences in the incidences of other SAEs were identified among the treatment groups. The present meta-analysis provides preliminary evidence for the comparative safety and efficacy of HAIC and TACE combined with sorafenib, and indicates the dominance of HAIC-oxaliplatin in HCC interventional therapy. However, high-quality RCTs are required to further confirm the efficacy of HAIC-oxaliplatin. The present study has been registered with PROSPERO (registration no. CRD42021288497)., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Chen et al.)

The development of stable and efficient non-noble metal-based photocatalysts for water splitting is currently a key but challenging process for effective conversion and storage of sustainable energy. Here, we designed a new non-noble metal composite photocatalyst by covalently connecting nickel molecular ligand (NiL) to the graphitized carbon nitride (CN) framework for photocatalytic hydrogen evolution under visible light irradiation. Compared to CN, NiL-modified CN (NiL/CN) shows excellent photogenerated carrier migration rate. Without Pt as a co-catalyst, NiL/CN exhibits high photocatalytic activity (23.4 μmol h -1 ) with high stability. Experiments and theoretical calculations disclose that ligand-metal charge transfer (LMCT) mechanism plays a key role on the enhancement of photocatalytic activity. This work provides a promising method for future designing low-cost, high-performance photocatalysts for hydrogen production under solar light., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Chemotherapy is a common approach for cancer treatment, but intrinsic genetic mutations in different individuals may cause different responses to chemotherapy, resulting in unique histopathological changes. The genetic mutation along with the distinct histopathological features may indicate new tumor entities. BCOR-CCNB3 sarcomas is a kind of Ewing-like sarcomas (ELS) occurring mostly in bone and soft tissues. No gene fusion other than BCOR-CCNB3 has been found in this type of tumor., Case Presentation: We herein report a case of 17-year-old male patient, presented with a mass on his left shoulder that was diagnosed as undifferentiated small round cell sarcoma according to core biopsy. The patient received 5 courses of preoperational chemotherapy, and the tumor was resected and analyzed. Primitive small round cells and larger myoid cells in the resected tumor tissue but not in biopsy were observed, and arterioles stenosis and occlusion were also detected, indicating a dramatic change of histopathological features of this tumor. In addition, the immunohistochemical results showed the altered staining patterns of BCOR, bcl2, CyclinD1, TLE1, AR, SMA, CD117, STAB2, CD56, and CD99 in tumor tissues after chemotherapy. Notably, RNA sequencing revealed a RNF213-SLC26A11 fusion in the tumor sample., Conclusions: The BCOR-CCNB3 sarcoma with RNF213-SLC26A11 fusion may indicate a subset of tumors that undergo histopathological changes in response to chemotherapy. More similar cases in the future may help to clarify the clinical meanings of RNF213-SLC26A11 fusion in BCOR-CCNB3 sarcomas and the underlying mechanisms., (© 2022. The Author(s).)

Background: Most of study regarding periampullary diverticulum (PAD) impact on endoscopic retrograde cholangiopancreatography (ERCP) therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients., Aim: To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD., Methods: Patients seen in two endoscopy centers (The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China, and Kyoto Second Red Cross Hospital, Kyoto, Japan) underwent ERCP treatment for the first time between January 2012 and December 2017. The characteristics of choledocholithiasis with PAD were compared between the two centers, and their ERCP procedures and therapeutic outcomes were analyzed., Results: A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD. Lots of clinical characteristics were significantly different between the two centers. The common bile duct (CBD) diameter was wider, choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients (14.8 ± 5.2 mm vs 11.6 ± 4.2 mm, 12.2 ± 6.5 mm vs 8.2 ± 5.3 mm, 45.3% vs 20.3%, P < 0.001 for all). In addition, concomitant diseases, such as acute cholangitis, gallbladder stones, obstructive jaundice, cholecystectomy, and acute pancreatitis, were significantly different between the two centers ( P = 0.03 to < 0.001). In the Lanzhou center, CBD diameter and choledocholithiasis size were lower, and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients (13.4 ± 5.1 mm vs 14.8 ± 5.2 mm, 10.3 ± 5.4 mm vs 12.2 ± 6.5, 39% vs 45.3%, 13.9% vs 18.5%, P = 0.002 to < 0.001). But all these characteristics were not significantly different in the Kyoto center. The proportions of endoscopic sphincterotomy (EST), endoscopic balloon dilatation (EPBD), and EST+EPBD were 50.5%, 1.7%, and 42.5% in the Lanzhou center and 90.0%, 0.0%, and 0.4% in the Kyoto center, respectively. However, the overall post-ERCP complication rate was not significantly different between the two centers (8.9% in the Lanzhou and 5.8% in the Kyoto. P = 0.12). In the Lanzhou center, the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group (35.3% vs 26.0%, P < 0.001). But the rate was no significant difference between the two groups in Kyoto center. The residual rates of choledocholithiasis were not significantly different between the two groups in both centers. Post-ERCP complications occurred in 8.9% of the PAD patients and 8.1% of the non-PAD patients in the Lanzhou Center, and it occurred in 5.8% in PAD patients and 10.0% in non-PAD patients in the Kyoto center, all P > 0.05., Conclusion: Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers. The patients had larger and multiple stones, wider CBD diameter, and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center. The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers. The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Low-dose amitriptyline (AMT) is an effective treatment for diarrhea-dominant irritable bowel syndrome (IBS-D). Its efficacy depends upon its serum concentration and the patient's CYP2C19 genotype., Aims: To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients., Methods: Ninety IBS-D patients were treated of AMT for 6 weeks. Efficacy was evaluated by the results of the Adequate Relief question each week and an IBS severity scoring system (IBS-SSS) at 0, 3, and 6 weeks. CYP2C19 genotyping was performed by direct sequencing. AMT and NT steady-state serum concentrations were detected by high-performance liquid chromatography., Results: The CYP2C19 polymorphism exhibited a significant influence on the NT serum concentration but did not predict the clinical efficacy of AMT for treating IBS-D. The NT steady-state and dose-corrected serum concentrations were significantly correlated with an improvement in the IBS-SSS score after 6 weeks, whereas the AMT serum concentration was not correlated with clinical improvement. The cut-off NT steady-state serum concentration of 2.91 ng/ml may help distinguish responders from non-responders., Conclusions: NT serum concentration but not CYP2C19 polymorphism may be correlated with the clinical efficacy of AMT for treating IBS-D, and such a response may occur at the upper NT threshold of 2.91 ng/ml., (Copyright © 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Mitochondria are indispensable for energy metabolism and cell signaling. Mitochondrial homeostasis is sustained with stabilization of mitochondrial membrane potential, balance of mitochondrial calcium, integrity of mitochondrial DNA, and timely clearance of damaged mitochondria via mitophagy. Mitochondrial dysfunction is featured by increased generation of mitochondrial reactive oxygen species, reduced mitochondrial membrane potential, mitochondrial calcium imbalance, mitochondrial DNA damage, and abnormal mitophagy. Accumulating evidence indicates that mitochondrial dysregulation causes oxidative stress, inflammasome activation, apoptosis, senescence, and metabolic reprogramming. All these cellular processes participate in the pathogenesis and progression of chronic respiratory diseases, including chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. In this review, we provide a comprehensive and updated overview of the impact of mitochondrial dysfunction on cellular processes involved in the development of these respiratory diseases. This not only implicates mechanisms of mitochondrial dysfunction for the pathogenesis of chronic lung diseases but also provides potential therapeutic approaches for these diseases by targeting dysfunctional mitochondria., Competing Interests: The authors declare no conflicts of interest, financial or otherwise., (Copyright © 2021 Wen-cheng Zhou et al.)

Objective: After bone prosthesis replacement, M1-type macrophage polarization can be induced by titanium (Ti) particles and produce inflammatory, leading to osteolysis. Adipocyte-derived exosomes (ADEs) exert immune-modulatory impact on the macrophage, while whether it can inhibit the macrophage polarization induced by Ti is unclear. This study focuses on the M1-type macrophage and aims to determine the effect of ADEs on Ti-induced M1-type macrophage polarization in osteolytic mice and the involved mechanism., Methods: Ti particle-induced osteolysis mouse model was established and macrophages were isolated from the osteolysis site. The levels of NLRP3 and specific markers for M1-type macrophage were determined. ADEs isolated from adipocyte cell line 3T3-L1, or conditioned ADEs with low-expressed miR-34a isolated from 3T3-L1 transfected with miR-34a inhibitor were co-cultured with RAW 264.7 to determine their impact on the polarization of macrophage., Results: ADEs reduced the M1-type macrophage polarization and caused the upregulation of miR-34a in macrophage of the osteolysis site of the osteolysis mouse model. Also, the level of miR-34a in ADEs was higher than that in the adipocyte. The conditioned ADEs expressed a low level of miR-34a and boosted the Ti-induced M1-type polarization. MiR-34a could target NLRP3 and negatively regulated its expression. Moreover, NLRP3 knockdown in macrophage restricted the conditioned ADEs to promote macrophage towards to Ti-induced M1-type polarization. The inhibitory function of ADEs on M1-type macrophage polarization was abolished by miR-34a silencing in the mouse osteolysis model., Conclusion: The miR-34a carried by ADEs reduced the polarization of M1-type macrophages by targeting macrophage NLRP3 during Ti particle-induced osteolysis., (© 2020 Wiley Periodicals LLC.)

Background and Purpose: Retinal pathological changes may precede or accompany the deterioration of brain tissue in Parkinson's disease (PD). The purpose of this meta-analysis was to assess the usefulness of optical coherence tomography (OCT) measurements as potential imaging biomarkers for PD., Methods: PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched for observational studies (published prior to 30 May 2020) comparing the OCT measurements between PD patients and healthy controls (HCs). Our main end-points were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell complex thickness, macular thickness and macular volume. Pooled data were assessed by use of a random-effects model., Results: A total of 36 observational studies were identified that included 1712 patients with PD (2548 eyes) and 1778 HCs (2646 eyes). Compared with the HC group, the PD group showed a significant reduction in mean pRNFL thickness (weighted mean difference [WMD] -3.51 μm, 95% confidence interval [CI] -4.84, -2.18; p = 0.000), all quadrants at the pRNFL (WMD range -7.65 to -2.44 μm, all p < 0.05), macular fovea thickness (WMD -5.62 μm, 95% CI -7.37, -3.87; p = 0.000), all outer sector thicknesses at the macula (WMD range -4.68 to -4.10 μm, all p < 0.05), macular volume (WMD -0.21 mm 3 , 95% CI -0.36, -0.06; p < 0.05) and macular ganglion cell complex thickness (WMD -4.18 μm, 95% CI -6.07, -2.29; p < 0.05)., Conclusions: Our pooled data confirmed robust associations between retinal OCT measurements and PD, highlighting the usefulness of OCT measurements as potential imaging biomarkers for PD., (© 2020 European Academy of Neurology.)

East Asia has highly diverse and endemic biota due to its complex geological and climatic history and its diversified topography. The continental and insular distributions of land snail genus Acusta in East Asia provide a good opportunity to compare the evolutionary processes in this group under different biogeographical conditions. In this study, we inferred the evolutionary history of the land snail genus Acusta by a molecular phylogeny and investigated how the palaeogeographic events shaped species diversity and the distribution of the Acusta genus within the island arc. A concatenated dataset generated from sequences of one nuclear (ITS2) and two mitochondrial (16S, COI) gene fragments, include most of nominal taxa of the genus, four related species and one outgroup. We constructed the phylogeny and the evolutionary history of the genus through maximum-likelihood and Bayesian inference methods, using a Bayesian molecular clock and ancestral range estimation. Our results suggested that currently recognized species in Acusta are polyphyletic. The traditionally accepted concept of the affinity of Acusta and Bradybaena is not supported. The hypothesis of colonization via land bridges during the Pleistocene glaciations for the biota of East Asian islands is not supported. Instead, the origin and diversification of the genus Acusta was dated to the late Miocene-Pliocene from an area around North and Northeast China to South China and East Asian islands Three major evolutionary lineages were identified. Two of the major lineages demonstrate distinct evolutionary histories, as sympatric speciation is the major speciation process for the continental clade, while the insular clade originated from founder events. Taiwan functioned as an important source of diversification for species on the East Asian islands possibly through passive dispersal of different mechanisms. The sea level fluctuations caused by the Pleistocene glacial cycles play a role in the subsequent dispersion and diversification of species of the continental clade, such as the more recent range expansion of A. redfieldi from South China to Taiwan and Japan., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: To observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia., Methods: Sixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively., Results: All items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI-symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p < 0.05). However, no differences were found in the frequency of NDI checklist, psychological status (HAMD/HAMA scores) of EPS, or sleep quality (PSQI score) between the two groups after treatment. In addition, the time to fall asleep was shorter in the AMT group compared with the RT group after 4 weeks of treatment (p < 0.05)., Conclusion: Low-dose AMT effectively improved the dyspepsia symptoms and the time to fall asleep in the EPS patients, compared with pantoprazole, although it did not reduce the psychological distress. Therefore, AMT could be considered as a good candidate for EPS treatment in the clinic.

Background: Although  Helicobacter pylori  (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages., Purpose: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer., Results: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer., Conclusion: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

In this study, four new dextral camaenid from China are reported, based on shell morphology, reproductive system anatomy, and molecular phylogenetic analyses: Camaena funingensis Zhou, Wang & Lin, sp. nov. , Camaena gaolongensis Zhou, Wang & Lin, sp. nov. , Camaena maguanensis Zhou, Wang & Hu, sp. nov. , and Camaena yulinensis Zhou, Wang & Hu, sp. nov. Detailed descriptions of the morphological characteristics including shells and genitalia, DNA sequences, and living environments of the four new species are provided, with further comparisons with congeners.

Background: An outbreak of Coronavirus Disease 2019 (COVID-19) which was infected by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is still spreading and has led to unprecedented health emergency over the world. Though no specific drug has been developed so far, emerging agents have been confirmed effective or potentially beneficial to restrain it. Lianhua Qingwen (LHQW) is a commonly used Chinese medical preparation to treat viral influenza, including in the fight against SARS in 2002-2003 in China. Recent data also showed that LHQW played a vigorous role in COVID-19 treatment., Purpose: This review will elucidate the pre-clinical and clinical evidence of LHQW in lung protection and antiviral activities, and provide timely data delivery for the exploration of effective treatment strategies in the therapy of COVID-19., Study Design and Method: The research data were obtained from the academic databases (up to August 8, 2020) including Pubmed, CNKI and Web of Science, on ethnobotany and ethno medicines. The search keywords for screening the literature information were "virus", "COVID-19", or "SARS-CoV-2", and "Lianhua Qingwen". The documents were filtered and summarized for final evaluation., Results: The collected evidence demonstrated that LHQW exhibited benefits against COVID-19. Impressively, LHQW in conjunction with conventional treatment could significantly improve COVID-19 patients as a synergetic strategy. The mechanisms were mainly involved the antiviral activity, and regulation of inflammation response as well as immune function., Conclusion: Although the data were far from adequate, the latest advances had shown the benefits of LHQW in COVID-19, especially in combination with other antiviral drugs. This review provides comprehensive evidence of LHQW as a complementary strategy for treating COVID-19. Nevertheless, imperious researches should be conducted to clarify the unconfirmed effects, regulatory mechanisms and adverse reactions of LHQW in treating COVID-19 by means of well designed randomized controlled trials., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Aims: Perioperative neurocognitive disorders (PND) are associated with cognitive impairment in the preoperative or postoperative period, and neuroinflammation is thought to be the most important mechanisms especially during the postoperative period. The GABAergic system is easily disrupted by neuroinflammation. This study investigated the impact of the GABAergic system on PND after anesthesia and surgery., Methods: An animal model of laparotomy with inhalation anesthesia in 16-month-old mice was addressed. Effects of the GABAergic system were assessed using biochemical analysis. Pharmacological blocking of α5GABA A Rs or P38 mitogen-activated protein kinase (MAPK) were applied to investigate the effects of the GABAergic system., Results: After laparotomy, the hippocampus-dependent memory and long-term potentiation were impaired, the levels of IL-6, IL-1β and TNF-α up-regulated in the hippocampus, the concentration of GABA decreased, and the protein levels of the surface α5GABA A Rs up-regulated. Pharmacological blocking of α5GABA A Rs with L655,708 alleviated laparotomy induced cognitive deficits. Further studies found that the P38 MAPK signaling pathway was involved and pharmacological blocking with SB203,580 alleviated memory dysfunctions., Conclusions: Anesthesia and surgery caused neuroinflammation in the hippocampus, which consequently disrupted the GABAergic system, increased the expressions of surface α5GABA A Rs especially through the P38 MAPK signaling pathway, and eventually led to hippocampus-dependent memory dysfunctions., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Aim: To evaluate the long-term efficacy of sublingual immunotherapy (SLIT) in treating mite-sensitized allergic rhinitis (AR). Materials & methods:  150 AR children were randomly divided into SLIT and pharmacotherapy (PT) groups, receiving a 3-year course of SLIT along with PT or PT only. Results: The symptom and medication scores at the 3- and 6-year follow-up were significantly lower compared with the baseline levels in both groups, while the values were significantly lower in SLIT group than in PT group. No significant differences were observed between 3- and 6-year follow-up in SLIT group. Conclusion: 3-year SLIT along with PT appeared more effective compared with PT only for mite-induced AR in children, and the treatment was effective for at least 3 consecutive years even after SLIT ceased.

Background: Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited., Aim: To verify the clinical value of our newly proposed PAD classification., Methods: A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared., Results: A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01)., Conclusion: Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To investigate the role of miR-411-5p and miR-434-3p in osteoblast differentiation in particulate-induced osteolysis., Methods: A mouse model of osteolysis and an in vitro osteolysis model were constructed. The expressions of molecules were detected using qRT-PCR and western blot. Alkaline phosphatase (ALP) activity was measured using the ALP Assay Kit, and the bone mineralization was measured using alizarin red staining., Results: The expression of miR-411-5p and miR-434-3p was decreased in osteolysis mice and UHMWPE-induced mMSCs, while GATA4 protein expression was increased. Over-expression of miR-411-5p and miR-434-3p up-regulated the expressions of osteoblast gene markers, enhanced the ALP activity, promoted the bone mineralization of mesenchymal stem cells. In addition, miR-411-5p and miR-434-3p could target GATA4, and miR-411-5p/434-3p affected the expressions of osteoblast gene markers through GATA4 in vitro and in vivo., Conclusion: Overexpression of miR-411-5p and miR-434-3p promoted the osteoblast differentiation by inhibiting GATA4 expression., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Due to the "ceiling effect" of respiratory depression and the non-addictiveness, the consumption of dezocine is increasing quickly in the cancer surgery perioperative period for security and comfort reasons in China. Former studies find dezocine inhibits the norepinephrine transporters (NET) and serotonin transporters (SERT) and sigma-1opioid receptors. Given the complexity of the molecular mechanism, the effect of dezocine on tumor cells need to be studied. In this study, we investigated the effect of dezocine on HepG2 and Hep 3B liver cancer cell lines growth and glycolysis, and the molecular mechanisms behind., Methods: HepG2 and Hep 3B cells viability and migration were measured by CCK8, Wound healing and transwell assay, Extracellular acidification rate (ECAR) was used to index the aerobic glycolysis of liver cancer cells and western blot analysis showed protein expression levels in the cells. SC79, an agonist of Akt, and the siRNA silence of Akt1 aimed to regulate Akt1 activity and expression in the reverse experiments., Results: Dezocine played opposite roles in HepG2 and Hep 3B cells viability and migration in a concentration-dependent manner (P<0.01). Dezocine has diverse effects on aerobic glycolysis and adjusts the serine/threonine kinase 1 (Akt1)-glycogen synthase kinase-3β (GSK-3β) pathway. The effects of SC79 and the siRNA silence of Akt1 could reverse the effects of dezocine on HepG2 and Hep 3B cells., Conclusions: As an analgesic drug widely used in clinical practice, dezocine play reversed roles on HepG2 and Hep 3B cells viability and migration targeting Akt1/GSK-3β pathway then the glycolysis in a concentration-dependent manner., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm.2020.03.28). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

The surgical suture has long been used to reconnect the injured tissues to restore their structure and function. However, its utility remains challenging in many areas, such as surgical site infections and minimally invasive surgeries. Herein, we report a novel surgical suture that possesses both antibacterial activity and shape memory effect to address these issues. In detail, natural antibacterial berberine was incorporated directly into the spinning solution of shape memory polyurethane with a near body transition temperature, and then berberine-containing polyurethane (BP) fibers were prepared by a facile one-step wet-spinning method for surgical suture. The prepared BP fibers were micro-sized and characterized by their transition temperature, morphology, water contact angles, mechanical properties, in vitro shape memory effect, drug release, and antibacterial activity. The results showed that with the increasing amount of the incorporated berberine, the transition temperatures of the fibers were not significantly affected, remains at near body temperature, while the contact angles of the fibers were significantly decreased and the mechanical properties of the fibers were significantly weakened. The optimized fiber was selected to evaluate the cytotoxicity and in vivo biocompatibility before in vivo shape memory effect and wound healing capacity in a mouse skin suture-wound model was tested. Besides the shape memory effect, it was demonstrated that the fiber is capable of antibacterial activity and anti-inflammatory effect, and promoting wound healing. The mechanism of the antibacterial activity and anti-inflammatory effect of the fiber was discussed. Overall, it is expected that by the berberine added to the fiber for surgical suture, it will be more popular and extend the utility of the sutures in a wide range of clinical applications., (Copyright © 2020 Zhou, Tan, Chen, Cen, You, Tan, Li and Tian.)

Commercially available white light-emitting diodes (LEDs) have an intense emission in the range of blue light, which has raised a range of public concerns about their potential risks as retinal hazards. Distinct from other visible light components, blue light is characterized by short wavelength, high energy, and strong penetration that can reach the retina with relatively little loss in damage potential. Mitochondria are abundant in retinal tissues, giving them relatively high access to blue light, and chromophores, which are enriched in the retina, have many mitochondria able to absorb blue light and induce photochemical effects. Therefore, excessive exposure of the retina to blue light tends to cause ROS accumulation and oxidative stress, which affect the structure and function of the retinal mitochondria and trigger mitochondria-involved death signaling pathways. In this review, we highlight the essential roles of mitochondria in blue light-induced photochemical damage and programmed cell death in the retina, indicate directions for future research and preventive targets in terms of the blue light hazard to the retina, and suggest applying LED devices in a rational way to prevent the blue light hazard., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper.

The complete mitochondrial genome (mitogenome) of Chinese endemic snail Camaenella platyodon (Pfeiffer, 1846) has been sequenced and annotated in this study. The entire circular genome is 13,985 bp in size and represents the third camaenid mt genome, with 2 ribosomal RNA genes, 22 transfer RNA genes, 13 protein-coding genes. All of genes are divided into two groups, including 24 genes on the majority coding strand (J strand) and others on the minority coding strand (N strand). Phylogenetic analysis of 13 protein-coding genes suggests that C . platyodon is closely related to the species in family Camaenidae., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Early gastric cancer (EGC), compared with advanced gastric cancer (AGC), has a higher 5-year survival rate. However, due to the lack of typical symptoms and the difficulty in diagnosing EGC, no effective biomarkers exist for the detection of EGC, and gastroscopy is the only detection method., Aim: To provide new biomarkers with high specificity and sensitivity through analyzed the differentially expressed microRNAs (miRNAs) in EGC and AGC and compared them with those in benign gastritis (BG)., Methods: We examined the differentially expressed miRNAs in the plasma of 30 patients with EGC, AGC, and BG by miRNA chip analysis. Then, we analyzed and selected the significantly different miRNAs using bioinformatics. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) confirmed the relative transcription level of these miRNAs in another 122 patients, including patients with EGC, AGC, Helicobacter pylori ( H. pylori )-negative gastritis (Control-1), and H. pylori -positive atrophic gastritis (Control-2). To establish a diagnostic model for the detection of plasma miRNA in EGC, we chose miRNAs that can be used to determine EGC and AGC from Control-1 and Control-2 and miRNAs in EGC from all other groups., Results: Among the expression profiles of the miRNA chips in the three groups in the discovery set, of 117 aberrantly expressed miRNAs, 30 confirmed target prediction, whereas 14 were included as potential miRNAs. The RT-qPCR results showed that 14 potential miRNAs expression profiles in the two groups exhibited no differences in terms of H. pylori -negative gastritis (Control-1) and H. pylori -positive atrophic gastritis (Control-2). Hence, these two groups were incorporated into the Control group. A combination of four types of miRNAs, miR-7641, miR-425-5p, miR-1180-3p and miR-122-5p, were used to effectively distinguish the Cancer group (EGC + AGC) from the Control group [area under the curve (AUC) = 0.799, 95% confidence interval (CI): 0.691-0.908, P < 0.001]. Additionally, miR-425-5p, miR-24-3p, miR-1180-3p and miR-122-5p were utilized to distinguish EGC from the Control group (AUC = 0.829, 95%CI: 0.657-1.000, P = 0.001). Moreover, the miR-24-3p expression level in EGC was lower than that in the AGC (AUC = 0.782, 95%CI: 0.571-0.993, P = 0.029), and the miR-4632-5p expression level in EGC was significantly higher than that in AGC (AUC = 0.791, 95%CI: 0.574-1.000, P = 0.024)., Conclusion: The differentially expressed circulatory plasma miR-425-5p, miR-1180-3p, miR-122-5p, miR-24-3p and miR-4632-5p can be regarded as a new potential biomarker panel for the diagnosis of EGC. The prediction and early diagnosis of EGC can be considerably facilitated by combining gastroscopy with the use of these miRNA biomarkers, thereby optimizing the strategy for effective detection of EGC. Nevertheless, larger-scale human experiments are still required to confirm our findings., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest.

Sublingual immunotherapy (SLIT) has been widely used for the treatment of allergic respiratory diseases, but many problems remain unsolved. Currently available data suggest that SLIT is very effective in children and adults with IgE-mediated respiratory diseases. Most allergists in China generally believe that SLIT is suitable for allergic rhinitis and asthma due to its safety and tolerability. SLIT for three years is suitable for patients to acquire stable therapeutic effects, and the efficacy of single-allergen SLIT for polysensitized patients has also been confirmed. Nevertheless, there are still several factors restricting its application in China, such as the uncertainty of its long-term effects and the prevention of new sensitizations onset, the risk of asthma attacks, the low public awareness of SLIT and poor compliance by patients. This is a narrative review of current evidence on SLIT coming from China., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Light emitting diodes (LEDs) are widely used to provide illumination due to their low energy requirements and high brightness. However, the LED spectrum contains an intense blue light component which is phototoxic to the retina. Recently, it has been reported that blue light may directly impinge on mitochondrial function in retinal ganglion cells (RGCs). Mitochondria are high dynamic organelles that undergo frequent fission and fusion events. The aim of our study was to elucidate the role of mitochondrial dynamics in blue light-induced damage in retinal neuronal R28 cells. We found that exposure to blue light (450 nm, 1000 lx) for up to 12 h significantly up-regulated the expression of mitochondrial fission protein Drp1, while down-regulating the expression of mitochondrial fusion protein Mfn2 in cells. Mitochondrial fission was simultaneously stimulated by blue light irradiation. In addition, exposure to blue light increased the production of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP), and induced apoptosis in R28 cells. Notably, Drp1 inhibitor Mdivi-1 and Drp1 RNAi not only attenuated blue light-induced mitochondrial fission, but also alleviated blue light-induced ROS production, MMP disruption and apoptosis in cells. Compared with Mdivi-1 and Drp1 RNAi, the antioxidant N-acetyl-L-cysteine (NAC) only slightly inhibited mitochondrial fission, while significantly alleviating apoptosis after blue light exposure. Moreover, we examined markers for mitophagy, which is responsible for the clearance of dysfunctional mitochondria. It was found that blue light stimulated the conversion of LC3B-I to LC3B-II as well as the expression of PINK1 in R28 cells. Mdivi-1 or Drp1 RNAi efficiently inhibited the blue light-induced expression of PINK1 and co-localization of LC3 with mitochondria. Thus, our data suggest that mitochondrial fission is required for blue light-induced mitochondrial dysfunction and apoptosis in RGCs.

Aim: Multifactors contribute to the development of postoperative cognitive dysfunction (POCD), of which the most important mechanism is neuroinflammation. Prostaglandin E2 (PGE2) is a key neuroinflammatory molecule and could modulate hippocampal synaptic transmission and plasticity. This study was designed to investigate whether PGE2 and its receptors signaling pathway were involved in the pathophysiology of POCD., Methods: Sixteen-month old male C57BL/6J mice were exposed to laparotomy. Cognitive function was evaluated by fear conditioning test. The levels of PGE2 and its 4 distinct receptors (EP1-4) were assessed by biochemical analysis. Pharmacological or genetic methods were further applied to investigate the role of the specific PGE2 receptors., Results: Here, we found that the transcription and translation level of the EP3 receptor in hippocampus increased remarkably, but not EP1, EP2, or EP4. Immunofluorescence results showed EP3 positive cells in the hippocampal CA1 region were mainly neurons. Furthermore, pharmacological blocking or genetic suppression of EP3 could alleviate surgery-induced hippocampus-dependent memory deficits and rescued the expression of plasticity-related proteins, including cAMP response element-binding protein (CREB), activity-regulated cytoskeletal-associated protein (Arc), and brain-derived neurotrophic factor (BDNF) in hippocampus., Conclusion: This study showed that PGE2-EP3 signaling pathway was involved in the progression of POCD and identified EP3 receptor as a promising treatment target., (© 2018 John Wiley & Sons Ltd.)

The complete mitochondrial genome of the white garden snail Theba pisana (Müller, 1774) has been sequenced and annotated in this study. The entire circular genome is 14,795 bp in size and represents the first mitochondrial genome in the genus Theba , with two ribosomal RNA genes, 22 transfer RNA genes, 13 protein coding genes. All of genes are divided into two groups, including 24 genes on the majority coding strand (J strand) and others on the minority coding strand (N strand).The phylogeny supports the relationship of species in Helicidae., Competing Interests: No potential conflict of interest was reported by the authors., (© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Carcinogenesis is known to be primarily associated with gene mutations. Recently, increasing evidence has suggested that epigenetic events also serve crucial roles in tumor etiology. Environmental factors, including nutrition, toxicants and ethanol, are involved in carcinogenesis through inducing epigenetic modifications, such as DNA methylation, histone deacetylase and miRNA regulation. Studying epigenetic mechanisms has facilitated the development of early diagnostic strategies and potential therapeutic avenues. Modulation at the epigenetic level, including reversing epigenetic modifications using targeted drugs, has demonstrated promise in cancer therapy. Therefore, identifying novel epigenetic biomarkers and therapeutic targets has potential for the future of cancer therapy. The present review discusses the environmental factors involved in epigenetic modifications and potential drug candidates for cancer therapy.

Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase-9, caspase-3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β-Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase-9, caspase-3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase-9, caspase-3, p53, and p21. The shCCNB1 group had decreased proliferation and S-phase cell proportion and increased apoptosis, senescence, and G0/G1-phase cell proportion. The PFT-α group showed higher expressions of MDM2 and lower expressions of Bax, caspase-9, caspase-3, p53, and p21. The PFT-α group had increased proliferation and S-phase cell proportion and declined apoptosis, senescence, and G0/G1-phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC., (© 2018 Wiley Periodicals, Inc.)

NF-κB signaling pathway shows significant influence on wear particle-induced osteolysis, and this study aims to explore the underlying mechanism and the role of let-7f-5p in this process. A mouse calvarial osteolysis model was constructed with PMMA particles, and the bone marrow-derived macrophages (BMMs) were isolated from the osteolysis area. The expression of miRNA and protein was determined by qRT-PCR and western blot, respectively. The level of cytokines was evaluated with ELISA. Recombinant plasmids were transfected into cells for the endogenous expression of related genes. Dual-luciferase reporter assay was performed to determine the interaction between let-7f-5p and IL-10 in macrophage RAW264.7 cells. M1 macrophage polarization and expression of let-7f-5p were promoted in BMMs of osteolysis mouse model, compared with that in sham group. The expression of let-7f-5p was increased in the process of M1 macrophage polarization that induced by PMMA. Let-7f-5p was involved in M1 polarization in macrophages that treated with PMMA. IL-10 was negatively regulated by let-7f-5p. NF-κB regulated the expression of IL-10 through let-7f-5p. NF-κB participated in the PMMA-induced M1 macrophage polarization through let-7f-5p. Let-7f-5p contributed to PMMA-induced osteolysis by promoting M1 polarization of macrophages. The NF-κB/let-7f-5p/IL-10 pathway induces M1 macrophage polarization, and thus contributing to wear particle-induced osteolysis.

This report mainly focuses on the investigation of morphological, optical, and electrical properties of Al 2 O 3 /ZnO nanolaminates regulated by varying bilayer thicknesses. The growth mechanism of nanolaminates based on atomic layer deposition and Al penetration into ZnO layer are proposed. The surface roughness of Al 2 O 3 /ZnO nanolaminates can be controlled due to the smooth effect of interposed Al 2 O 3 layers. The thickness, optical constants, and bandgap information of nanolaminates have been investigated by spectroscopic ellipsometry measurement. The band gap and absorption edge have a blue shift with decreasing the bilayer thickness on account of the Burstein-Moss effect, the quantum confinement effect and the characteristic evolution of nanolaminates. Also, the carrier concentrations and resistivities are found to be modified considerably among various bilayer thicknesses. The modulations of these properties are vital for Al 2 O 3 /ZnO nanolaminates to be used as transparent conductor and high resistance layer in optoelectronic applications.

Pulmonary fibrosis is a devastating lung disorder with mysterious pathogenesis and limited treatment options. It is well-recognized that the uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts excessively produce extracellular matrix (ECM) proteins which contribute to the fibrosis change of the lungs. Thus, blocking ECM accumulation would delay fibrosis progression. In this study, we observed the effects of astragaloside IV (ASV) (10 mg/kg/d) on ECM proteins in bleomycin (BLM, 5 mg/kg)-treated rats. Our results showed that ASV not only ameliorated BLM-induced body weight loss, lung coefficient increase, histological changes and collagen secretion, but also reduced the levels of type III collagen (Col-III) in lung homogenate, laminin (LN) and hyaluronic acid (HA) in serum, as well as hydroxyproline (HYP) in lung tissue. Besides, ASV significantly down-regulated the levels of high-mobility group box1 (HMGB1) in serum and lung tissue, and inhibited the up-regulated expression of α-SMA (marker of myofibroblasts) in the lungs. Taken together, these findings indicate that ASV attenuates BLM-induced ECM deposition, supporting its use as a promising candidate to treat lung fibrosis.

Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/β-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt-mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor-β (TGF-β) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α-SMA and collagen I) and the TGF-β signalling pathway that include smad2/3 and its phosphorylated form p-smad2/3. Detailed analysis of the possible molecular mechanisms mediated by β-catenin revealed epithelial-mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of β-catenin in regulation of the signalling network, which acts to counteract autocrine TGF-β/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFβ1-smad2/3 signalling through Wnt/β-catenin contribute to lung fibrosis., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)