Aim To design and synthesize a series of phenylacetamide derivatives with different substituted phenylacetic acid as raw materials,and to investigate the protective effects of the compound on the damage of pancreatic β cells induced by palmitate acid(PA).Methods Min6 cells were cultured and divided into B blank control group,PA treatment group and PA+compounds group.The viability of Min6 cells was de-tected by CCK-8.The protein expressions of TXNIP and NLRP3 were observed by Western blot.MDA con-tent and SOD activity were detected by MDA and SOD kit.The insulin secretion of Min6 islet cells was meas-ured with insulin ELISA kit.Results A total of 10 phenylacetamide derivatives were designed and synthe-sized.Their structures were confirmed by 1H NMR and ESI-MS.Pharmacological activity study showed that most of the compounds had protective effects on islet βcells,among which LY-6 and LY-8 had stronger pro-tective effects than PA model group,with the cell via-bility of 61.4％,and LY-6 had the highest cell activi-ty,reaching to 104.9％.Compared with PA group,the protein expression of TXNIP and NLRP3 decreased in LY-6 and LY-8 groups,MDA content decreased and SOD activity increased,and insulin secretion of Min6 cell increased.Conclusions LY-6 and LY-8 inhibit TXNIP expression and decrease the activation of NL-RP3 inflammasome,and decrease the production of MDA and increase SOD activity,and thus reducing is-let β cells apoptosis and increasing insulin secretion.Therefore,the compound LY-6 could serve as a poten-tial anti-diabetic new chemical entity.

In infants with severe bronchopulmonary dysplasia(sBPD),severe pulmonary lobar emphysema may occur as a complication,contributing to significant impairment in ventilation.Clinical management of these infants is extremely challenging and some may require lobectomy to improve ventilation.However,prior to the lobectomy,it is very difficult to assess whether the remaining lung parenchyma would be able to sustain adequate ventilation postoperatively.In addition,preoperative planning and perioperative management are also quite challenging in these patients.This paper reports the utility of selective bronchial occlusion in assessing the safety and efficacy of lobectomy in a case of sBPD complicated by severe right upper lobar emphysema.Since infants with sBPD already have poor lung development and significant lung injury,lobectomy should be viewed as a non-traditional therapy and be carried out with extreme caution.Selective bronchial occlusion test can be an effective tool in assessing the risks and benefits of lobectomy in cases with sBPD and lobar emphysema.However,given the technical difficulty,successful application of this technique requires close collaboration of an experienced interdisciplinary team.

BACKGROUND:Compared with traditional two-dimensional culture,three-dimensional microtissue culture can show greater advantages.However,more favorable cultivation methods in three-dimensional culture still need to be further explored. OBJECTIVE:To evaluate the cell behavior of microtissue and its ability to promote cartilage formation under two three-dimensional culture methods. METHODS:Cartilage-derived microcarriers were prepared by chemical decellularization and tissue crushing.DNA quantification and nuclear staining were used to verify the success of decellularization,and histological staining was used to observe the matrix retention before and after decellularization.The microcarriers were characterized by scanning electron microscopy and CCK-8 assay.Cartilage-derived microtissues were constructed by combining cartilage-derived microcarriers with human adipose mesenchymal stem cells through three-dimensional static culture and three-dimensional dynamic culture methods.The cell viability and chondrogenic ability of the two groups of microtissues were detected by scanning electron microscopy,live and dead staining,and RT-qPCR. RESULTS AND CONCLUSION:(1)Cartilage-derived microcarriers were successfully prepared.Compared with before decellularization,the DNA content significantly decreased after decellularization(P<0.001).Scanning electron microscope observation showed that the surface of the microcarrier was surrounded by collagen,maintaining the characteristics of the natural extracellular matrix of cartilage cells.CCK-8 assay indicated that microcarriers had no cytotoxicity and could promote cell proliferation.(2)Scanning electron microscopy and live and dead staining results showed that compared with the three-dimensional static group,the three-dimensional dynamic group had a more extended morphology of microtissue cells,and extensive connections between cells and cells,between cells and matrix,and between matrix.(3)The results of RT-qPCR showed that the expressions of SOX9,proteoglycan,and type Ⅱ collagen in microtissues of both groups were increased at 7 or 14 days.The relative expression levels of each gene in the three-dimensional dynamic group were significantly higher than those in the three-dimensional static group at 14 days(P<0.05).At 21 days,the three-dimensional static group had significantly higher gene expression compared with the three-diomensional dynamic group(P<0.001).(4)The results showed that compared with three-dimensional static culture microtissue,three-dimensional dynamic culture microtissue could achieve higher expression of chondrogen-related genes in a shorter time,showing better cell viability and chondrogenic ability.

Objective Pancreatic cancer(PC)is a malignant tumor of the digestive tract that is difficult to diagnose early,easily metastasizes and relapses,and resistant to conventional chemotherapy.PC is a very difficult disease to treat.The key regulatory factors of PC resistance,such as epithelial-mesenchymal transition phenotypic cells,tumor stem cells,and miRNAs,have been reviewed in the past few years,and some new regulatory factors have been discovered as supplements.This review mainly focuses on the characteristics and properties of the key regulatory factors of PC chemotherapy resistance including long noncoding RNAs,nuclear factor KB and exosomes,drug resistance mechanisms,and treatment related strategies,and future treatment directions were predicted.

With the aging of population intensifies and the level of population health have improved, thus much attention has been directed to how to delaying or preventing skin aging. Skin aging is associated with age, ultraviolet and lifestyle, mainly characterized as skin sagging, wrinkles, pigmentation, so it is urgent to seek traditional Chinese medicine and related cosmetics to solve the problem of skin aging. Traditional Chinese medicine has the functions of anti-oxidation, enhancing human immunity, promoting body metabolism and regulating endocrine, therefore, it has become a research focus in anti-skin aging. This article reviews the skin aging mechanism and the research advances of traditional Chinese medicine anti-skin aging, in order to provide a reference for future research and development of anti-aging traditional Chinese medicine.

This study aims to improve the solubility and bioavailability of daidzein by preparing the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocrystals. Specifically, the nanocrystals were prepared with daidzein as a model drug, PEG_(20000), Carbomer_(940), and NaOH as a plasticizer, a gelling agent, and a crosslinking agent, respectively. A two-step method was employed to prepare the β-cyclodextrin-daidzein/PEG_(20000)/Carbomer_(940) nanocystals. First, the insoluble drug daidzein was embedded in β-cyclodextrin to form inclusion complexes, which were then encapsulated in the PEG_(20000)/Carbomer_(940) nanocrystals. The optimal mass fraction of NaOH was determined as 0.8% by the drug release rate, redispersability, SEM morphology, encapsulation rate, and drug loading. The inclusion status of daidzein nanocrystals was determined by Fourier transform infrared spectroscopy(FTIR), thermogravimetric analysis(TGA), and X-ray diffraction(XRD) analysis to verify the feasibility of the preparation. The prepared nanocrystals showed the average Zeta potential of(-30.77±0.15)mV and(-37.47±0.64)mV and the particle sizes of(333.60±3.81)nm and(544.60±7.66)nm before and after daidzein loading, respectively. The irregular distribution of nanocrystals before and after daidzein loading was observed under SEM. The redispersability experiment showed high dispersion efficiency of the nanocrystals. The in vitro dissolution rate of nanocrystals in intestinal fluid was significantly faster than that of daidzein, and followed the first-order drug release kinetic model. XRD, FTIR, and TGA were employed to determine the polycrystalline properties, drug loading, and thermal stability of the nanocrystals before and after drug loading. The nanocrystals loaded with daidzein demonstrated obvious antibacterial effect. The nanocrystals had more significant inhibitory effects on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa than daidzein because of the improved solubility of daidzein. The prepared nanocrystals can significantly increase the dissolution rate and oral bioavailability of the insoluble drug daidzein.
Sodium Hydroxide ; Acrylic Resins ; Escherichia coli ; Nanoparticles

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.
Colorectal Neoplasms/surgery* ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms/surgery* ; Retrospective Studies

Objective: To investigate the efficacy and safety of left bundle branch pacing(LBBP) in patients after transcatheter aortic valve implantation (TAVI). Methods: This is a retrospective study. A total of 35 patients underwent TAVI and received pacemaker implantation from January 2018 to December 2020 in Beijing Fuwai Hospital were enrolled. Patients were divided into LBBP group (n=12) and right ventricular apex pacing (RVAP) group (n=23) according to the pacing position. The success rate of operation in LBBP group was calculated, and the occurrence of complications were observed, and the parameters of pacemaker were measured on the 3rd day and 1, 3 and 6 months after operation. The N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiographic and ECG indexes were compared between the two groups on the 3rd day and 1, 3, and 6 months after pacemaker implantation. Result: A total of 35 patients were included, The age was (76.4±7.7) years, including 19 males (54.3%). The procedure time ((86.58±17.10)min vs. (68.74±9.18)min, P<0.001) and fluoroscopy duration ((20.08±4.44)min vs. (17.00±2.26)min, P<0.001) were significantly longer in LBBP group compared with RVAP group. The operation success rate of LBBP group was 11/12. There was no serious operation related complications such as pneumothorax, hemothorax, electrode dislocation, infection, and lower limb bleeding. The patients were followed up for 7.43 (5.21, 9.84) months. The programmed parameters of pacemaker were in the ideal range and stable during follow-up. At 3 and 6 months after operation, the left ventricular ejection fraction in LBBP group was higher than that in RVAP Group (at 3 months: (60.75±2.89)% vs. (57.35±3.33)%, P=0.004; at 6 months: (63.17±3.33)% vs. (56.17±3.97)%, P<0.001), NT-proBNP values was lower in LBBP group than that in RVAP Group (at 3 months: 822 (607, 1 150)ng/L vs. 1 052 (902, 1 536)ng/L, P=0.006; at 6 months: 440 (330,679)ng/L vs. 783 (588, 1 023)ng/L, P=0.001). At 1, 3 and 6 months after operation, the QRS duration was shorter in LBBP group than that in RVAP group (1 month: 99 (97, 107)ms vs. 126(124, 130)ms, P<0.001; 3 months: 98(96, 105)ms vs. 129(128, 133)ms, P<0.001; 6 months: 96(94, 104)ms vs. 130(128, 132)ms, P<0.001). Conclusions: For patients with permanent pacemaker indications after TAVI, LBBP is feasible, safe and reliable. It could improve the cardiac function in the short term, the long-term effect of LBBP needs to be further observed.
Aged ; Aged, 80 and over ; Bundle of His ; Cardiac Pacing, Artificial/methods* ; Electrocardiography/methods* ; Fluoroscopy ; Humans ; Male ; Retrospective Studies ; Stroke Volume ; Transcatheter Aortic Valve Replacement/adverse effects* ; Treatment Outcome ; Ventricular Function, Left