Objective To design and synthesize novel Hsp90 inhibitors with dual functions of synergistically enhancing the antifungal activity of fluconazole （FLC） against drug-resistant fungi and anti-tumor activity based on the Hsp90 inhibitor Ganetespib. Methods The previous research found that Ganetespib had a good synergistic anti-resistant fungal activity with FLC, with a fractional inhibitory concentration index （FICI） of 0.023 to 0.039. In this study, structural modifications were made to Ganetespib by replacing its indole ring with a phenyl ring containing different substituents to design and synthesize a series of new compounds. The in vitro synergistic anti-resistant fungal activity against C. albicans 0304103 in combination with FLC, anti-tumor activity （against HEL, HL60 and A549 cells）, and Hsp90α inhibition activity were determined to explore their structure-activity relationship and mechanism of action. Results The chemical structures of 19 new compounds were confirmed by ¹H NMR, ¹³C NMR and HRMS. Most of the compounds exhibited strong Hsp90α inhibitory activity, good synergistic activity against drug-resistant fungi in combination with FLC and anti-tumor activity. The substitution of electron-donating groups on the benzene ring was beneficial to enhancing the synergistic activity against drug-resistant fungi in combination with FLC. Among them, compounds F3 and F5 showed excellent synergistic activity against drug-resistant fungi in combination with FLC （FICI were both 0.047） and anti-tumor activity （IC₅₀ were 0.025 to 0.15 μmol/L and 0.021 to 0.23 μmol/L respectively）, and could down-regulate the expression levels of drug resistance genes and efflux pump genes in fungi, inhibit the formation of fungal biofilms, and arrest the cell cycle of HEL cells at G0/G1 phase. Conclusion The novel Hsp90 inhibitors such as F3 and F5 could both effectively exert the dual activities of synergizing with FLC to combat drug-resistant fungi and fight against tumors, which provided a new idea for the development of new drugs with dual functions of synergizing with FLC to combat drug-resistant fungi and fight against tumors.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.

Objective:To develop an artificial intelligence (AI) quality control model of fetal heart in the first trimester and verify its effectiveness.Methods:A total of 18 694 images of the four-chamber view(4CV) and three-vessel and tracheal view(3VT) of fetal heart in the first trimester were selected from Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University since January 2022 to December 2022. A total of 14 432 images were manually annotated. The one-stage target detection algorithm YOLO V5 was used to train the AI quality control model in the first trimester of fetal heart, and 4 262 images (golden standard set by expert group) were used to evaluate the application effectiveness of AI quality control model. Kappa consistency test was used to compare the results of section classification and standard degree judgment from AI quality control model, Doctor 1(D1) and Doctor 2(D2).Results:①Precision of the AI quality control model was 0.895, recall was 0.852, mean average precision (mAP 50) was 0.873.The average precision(AP) of the AI quality control model for section classification was 0.907 (4CV) and 0.989 (3VT), respectively. ②Compared with the gold standard, the overall coincidence rate and consistency of section classification of AI quality control model, D1 and D2 were 99.91% (Kappa=0.998), 100% (Kappa=1.000), 100% (Kappa=1.000), respectively. The coincidence rate and consistency of the plane standard degree evaluation from the AI quality control model, D1 and D2 were 97.46% (Weighted Kappa=0.932), 93.73% (Weighted Kappa=0.847), and 93.12% (Weighted Kappa=0.832), respectively. Strong consistency was displayed. Moreover, AI quality control model showed the highest coincidence rate and the strongest consistency in judging section standard degree, which was superior to manual quality control. The time-consuming of AI quality control (0.012 s/sheet) was significantly less than the way of manual quality control (4.76-6.11 s/sheet)( Z=-8.079, P<0.001). Conclusions:The use of artificial intelligent fetal heart quality control model in the first trimester can effectively and accurately control the image quality.

Objective:To summarize the perioperative nursing experience of a patient with hemophilia arthritis complicated with hepatitis C undergoing unilateral hip and knee arthroplasty at the same time.Methods:In August 2018, a patient with hemophilic arthritis complicated with hepatitis C was admitted to the first hospital of Lanzhou University. Preparations for health education, functional exercises, examination and evaluation before operation was made. Unilateral hip and knee arthroplasty were performed at the same time, strengthen the management of incisions and catheters after the operation, actively prevent complications, and guide patients to perform functional rehabilitation exercises under the conditions of good pain management and safe coagulation factor activity; pay attention to the nursing of coagulation factor replacement treatment in the whole perioperative period.Results:After careful nursing, no serious complications occurred during the patient's hospitalization, and the position and force line of the prosthesis were satisfactory by imaging examination before discharge.Conclusion:The perioperative care of this patient proved that the above-mentioned nursing measures are effective for hemophilic arthritis patients with hepatitis C undergoing unilateral hip and knee arthroplasty at the same time.

The skin is the largest organ of the human body and consists of two layers: epidermis and dermis. The dermal fibroblasts originate from distinct locations of the embryo and contain the location memory information in the skin. The dermal fibroblast progenitors differentiate into various cell types that are fated to perform specific functions such as hair follicle initiation and scar formation during wound healing. In addition, other skin components such as adipose tissue and nerves also play a role in wound healing. The authors reviewed the skin structure and its relationship with wound healing, and explored the mechanism of skin structure, such as epidermis, dermis and fat, in regulating the process of wound regeneration or scar healing, in order to find ways to promote wound healing or improve the quality of healing.

The skin is the largest organ of the human body and consists of two layers: epidermis and dermis. The dermal fibroblasts originate from distinct locations of the embryo and contain the location memory information in the skin. The dermal fibroblast progenitors differentiate into various cell types that are fated to perform specific functions such as hair follicle initiation and scar formation during wound healing. In addition, other skin components such as adipose tissue and nerves also play a role in wound healing. The authors reviewed the skin structure and its relationship with wound healing, and explored the mechanism of skin structure, such as epidermis, dermis and fat, in regulating the process of wound regeneration or scar healing, in order to find ways to promote wound healing or improve the quality of healing.

Objective: To evaluate the influence of enhanced recovery after surgery (ERAS) nursing model for perioperative patients in orthopedic surgery on complications. Methods: Computer-based search of electronic databases the Cochrane Library, PubMed, Embase, Web of Science, CNKI, WF and CBM Database to search for randomized controlled trials on the application of ERAS nursing models in orthopaedic patients at domestic and foreign before March 16, 2018, data were selected and screened according to the inclusion and exclusion criteria. RevMan 5.3 was used for meta-analysis of the included studies. Results: A total of 25 RCTs were included in the study and a total of 2 412 patients were included. Meta-analysis showed that the incidence of deep venous thrombos[RR=0.38, 95%CI(0.24, 0.61), P<0.01], and incidence of pulmonary infection[RR=0.26, 95% CI (0.10, 0.67), P=0.005], incidence of urinary tract infections[RR=0.28, 95%CI(0.10,0.78), P=0.01], incidence of constipation [RR=0.30, 95% CI (0.17,0.56), P=0.0001], The incidence of bloating [RR=0.35, 95%CI(0.13, 0.95), P=0.04], they were lower in the experimental group than in routine care, they were statistically significant. Incidence of incision infection [RR=0.75, 95% CI(0.17, 3.27), P= 0.70], incidence of pressure sores [RR=0.34, 95% CI(0.09, 1.27), P=0.11], incidence of nausea and vomiting [RR=0.81, 95% CI(0.52, 1.25), P=0.34] were not statistically significant; postoperative hospital stay, hospitalization costs, and patient satisfaction were statistically significant. Conclusions Compared with routine care, the ERAS nursing model can promote the recovery of orthopedic patients during perioperative period, reduce postoperative deep venous thrombosis, constipation, pulmonary infection, urinary tract infection, postoperative hospital stay, hospitalization costs, and patient satisfaction. All have a positive impact, but more multicentre and large sample clinical trials are needed for validation.

ObjectiveTo investigate the association of the genetic variation of the long non-coding RNA HOX transcript antisense RNA (HOATIR) and gene-environment interaction with prognosis-related clinical features of liver cancer. MethodsA total of 923 patients with primary liver cancer Shunde Hospital of Southern Medical University were admitted to a hospital from October 2010 to October 2016 were enrolled in this study. TaqMan quantitative PCR was used to detect HOTAIR rs17105613 T＞C, rs12427129 C＞T, and rs3816153 G＞T genotypes. The chi-square test was used to analyze the difference in the distribution of clinical features of liver cancer, and the logistic regression model was used to analyze the influence of the genetic variation of HOTAIR on the TNM stage of liver cancer, portal vein tumor thrombus, and age of onset. ResultsAfter the adjustment for environmental factors, rs17105613 and rs3816153 were significantly associated with TNM stage in the recessive mode (P＜005), and there was a statistically significant multiplicative interaction between rs12427129 and smoking on the age of onset of liver cancer (P=0.029), as well as an additive interaction with critical statistical significance (P=0.092). ConclusionHOTAIR rs17105613 and rs3816153 may be associated with TNM stage of liver cancer. The interaction between rs12427129 and smoking may influence the age of onset of liver cancer. Therefore, the genetic variation of HOTAIR may promote the invasion and metastasis of hepatoma cells.

Objective To design and prepare 13 ,15-cycloimides chlorin p6 (1) ,a class of chlorin related antitumor photo-sensitizers ,which contain a more stable six-membered cyclic imide comparing to the exocyclic anhydride ring of purpurin-18 (2) .Compounds (1) exhibit strong absorption at long wavelengths near λmax 700 nm to take full advantage of greater tissue penetration .Methods Pheophorbide a (3) was obtained by acid hydrolysis of chlorophyll a ,which was from crude chlorophyll extracts of Chinese traditional herb named Silkworm excrement .Purpurin-18 (2) was prepared by air oxidation and alkali open loop simultaneously on five-membered beta-keto carboxylic ester ring of pheophorbide a (3) .Finally ,the target compounds 1a~1j were synthesized via condensation of its anhydride ring with various amines including carboxyl-protected amino acids . Results Target compounds 1a~1j were successfully synthesized in yields ranged from 32 .6% to 65 .2% .Their structures were confirmed by elemental analysis ,ESI-MS and 1 H NMR spectra .Conclusion Treatment of purpurin-18 (2) with amines can produce target compounds 1a~1j .The starting raw material was inexpensive and readily available .The reaction conditions were mild and workup was convinient .

OBJECTIVETo investigate the relationship between homocysteine (Hcy), von willebrand factor (vWF), soluble intercellular adhesion molecule-1 (sICAM-1) and the risk of cardio-cerebrovascular events among Inner Mongolians.

METHODSA survey was conducted among 2 589 Inner Mongolians from May 2002 to June 2003, and they were followed up for about ten years. The 182 individuals who developed cardio-cerebrovascular events in the cohort were defined as cases and those whose age, gender and residence 1:1 matched to cases were selected from the individuals who did not developed cardio-cerebrovascular events as controls. Then, a nested case-control study was used to analyze the relationship between Hcy, vWF and sICAM-1 and risk of cardio-cerebrovascular events. Conditonallogistic regression analysis was used to calculate OR values and 95% CI.

RESULTSThe cases had a higher baseline blood pressure, higher prevalence of hypertension and family history of hypertension compared to controls (all P values < 0.05), however, there were no significantly different between TC, TG, LDL-C, HDL-C, FBG, smoking and drinking rates (all P values > 0.05). The M (P(25)-P(75)) of Hcy were 10.68 (7.84-14.98) and 10.02 (6.64-13.94) µmol/L, vWFs were 10.88 (8.14-14.58) and 10.42 (7.97-13.50) mg/L, sICAM-1 were 336.48 (260.68-409.87) and 335.12 (269.87-409.87) ng/ml. They were not significantly different between the two groups (Z values were 0.89, 0.94 and 0.29, respectively, all P values >0.05). After adjustment for the family history of hypertension, hypertension, TC, FPG, BMI, smoking and drinking rate, the conditional logistic regression showed that OR (95% CI) of risk of cardio-cerebrovascular events were 1.00 (0.52-1.93), 2.37 (1.25-4.49), and 0.81 (0.45-1.47) for the participants with increased Hcy, vWF, and sICAM-1, compared with those with normal Hcy, vWF, and sICAM-1, respectively.

CONCLUSIONIn the Inner Mongolians, increased vWF at baseline may increase the risk of cardio-cerebrovascular events, and increased Hcy and sICAM-1 were not significantly associated with the risk of cardio-cerebrovascular events.

Cardiovascular Diseases ; Case-Control Studies ; Cytokines ; Homocysteine ; Humans ; Hypertension ; Intercellular Adhesion Molecule-1 ; Logistic Models ; Prevalence ; Risk ; Risk Factors ; Stroke ; von Willebrand Factor