OBJECTIVE To prepare and characterize curcumin nanomicelles （hereinafter referred to as Cur/mPEG-PBLA micelles）， and to evaluate the in vitro hepatoprotective activity against alcohol liver disease （ALD）. METHODS Cur/mPEG-PBLA micelles were prepared with the dialysis method using methoxy-poly（ethylene glycol）-poly（β-benzyl-L-aspartate） （mPEG-PLGA） as the carrier. The appearance and microscopic morphology of Cur/mPEG-PBLA micelles were observed， and particle size， polydispersity index， Zeta potential， encapsulation efficiency and drug loading content were all detected. The in vitro release， pH stability， thermal stability， dilution stability， storage stability， plasma stability tests， and hemolysis experiments were all performed. The cell model of ALD was established with anhydrous ethanol intervention using human liver cancer cells and normal liver cells as objects， Cur reference solution as reference， to evaluate in vitro preventive and ameliorative effects of Cur/mPEG- PBLA micelles on ALD. RESULTS The prepared Cur/mPEG-PBLA micelles exhibited a pale-yellow milky light， with a spherical shape and uniform distribution. The average particle size was about 140 nm， and the polydispersity index was less than 0.3. Zeta potential was （－8.15±0.05） mV； the encapsulation efficiency was （73.26±3.16）%， and the drug loading content was （4.87± 0.42）%. The cumulative release of Cur reference substance was close to 80% at 10 h； the cumulative release of Cur/mPEG-PBLA micelles at 8 h was 28.94% and only 48.25% at 48 h. pH stability and thermal stability of Cur/mPEG-PBLA micelles were better than those of Cur reference solution； Cur/mPEG-PBLA micelles showed good dilution stability， storage stability and plasma stability， and would not cause hemolysis. Cur reference solution and Cur/mPEG-PBLA micelles had varying degrees of in vitro preventive and ameliorative effects on ALD in two types of cells； after 48 h of application， the above effects of Cur/mPEG-PBLA micelles were significantly better than those of Cur reference solution at the same mass concentration （P＜0.05）. CONCLUSIONS Cur/mPEG-PBLA micelles can improve pH stability and thermal stability of Cur， delayits degradation rate， and have better in vitro hepatoprotective activity against ALD.

In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma， this article systematically analyzes the historical evolution of the name， origin， harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica， prescription books， medical books and modern literature. The research results showed that Baiji（白及） was the main name， some scholars took Baiji（白芨） as its main name， and there were many other names such as Baiji（白给）， Baigen（白根）， Baiji（白苙）. The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata， and drying， large， white， solid， root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials， there were certain differences between their traits， and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed， with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn， and harvested in autumn was better. The processing and processing technology is relatively simple， and it was used fresh or powdered in past dynasties， while it is mainly sliced for raw use in modern times. Based on the results， it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas， and it should be uniformly written as Baiji（白及）. And if the original formula indicates the requirement of processing， it should be operated according to the requirement， if the requirement of processing is not indicated， it can be used in raw form as medicine.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective To investigate the relationship between gene mutation characteristics and immunological markers in patients with small cell lung cancer.Methods From January 2019 to 2020,155 patients with small cell lung cancer were admitted.Gene mutations were detected in these patients using target gene capture and sequencing method.Moreover,the tumor mutational burden(TMB)and expression of PD-L1 in some patients were detected.Results A total of 326 gene mutations were detected in the patients,the most significant of which were TP53 and RB1.Among the 8 genes with mutation frequency higher than 15％,patients with KMT2D,KMT2C,FAT1 and NOTCH1 mutations had higher TMB than those without mutation,and the difference was statistically significant(P＜0.05).Conclusion The most common mutated genes in patients with small cell lung cancer are TP53 and RB1.KMT2D,KMT2C,FAT1 and NOTCH1 may be potential markers for the efficacy of immunotherapy in small cell lung cancer.

Objective:To establish a classification system for the repair band in the subchondral bone origination point in MRI for traumatic osteonecrosis of the femoral head (ONFH) and preliminarily explore the correlation between this classification and the progression of femoral head collapse.Methods:A retrospective analysis was conducted on 73 cases of traumatic ON-FH treated at the Quanzhou Orthopedic-traumatological hospital from January 2000 to December 2019. Among them, there were 46 males and 27 females with an average age of 34.9±8.3 years (range 19-55 years). Clinical and radiological data such as age, gender, side, fracture classification, reduction quality, JIC classification, and bone repair band (BRB) classification were recorded. The progression of traumatic ONFH was assessed using the ARCO staging system, with stages IIIA and IIIB defined as mild collapse and progressive collapse, respectively. The BRB classification was established based on MRI findings, and the inter- and intra-observer consistency of the BRB classification was analyzed using Kappa test. The correlation between the BRB classification and progressive femoral head collapse was analyzed using the Kaplan-Meier survival curve and binary variable Cox regression analysis.Results:According to the BRB classification, 73 cases were divided into type 1 with superficial lesion in 38.4%, type 2 with uncertain lesion in 21.9%, and type 3 with extensive lesion in 39.7%. The inter-observer consistency Kappa value for the BRB classification was 0.798, and the intra-observer consistency Kappa value was 0.896, indicating a high level of consistency. A follow-up of 73 cases (54.8±34.9 months, range 24-165 months) showed a significant correlation between the BRB classification and ARCO staging at the last follow-up (χ 2=37.556, P<0.001), with progression to stages IIIA and IIIB as follows: type 1 had 3 and 1 cases, type 2 had 4 and 1 cases, and type 3 had 14 and 12 cases, respectively. Using the occurrence of progressive collapse (stage IIIB) as the endpoint, the risk of progression to stage IIIB for type 2 was not statistically different from type 1 [ HR=1.766, 95% CI (0.465, 6.702), P=0.403]; the risk of progression to stage IIIB for type 3 was significantly higher than for type 1 [ HR=15.126, 95% CI (4.708, 48.592), P<0.001]. Conclusion:The BRB classification is closely related to the progression of traumatic ONFH and is an independent risk factor for predicting the occurrence of progressive collapse; this classification is helpful for early diagnosis and predicting the progression of collapse and treatment plan decision-making.

Objective:To investigate the high-risk factors affecting the prognosis of patients with pT 1-2N 1M 0 after mastectomy, establish a nomogram prediction model, perform risk stratification, and screen the radiotherapy benefit populations. Methods:Clinical data of 936 patients with pT 1-2N 1M 0 breast cancer undergoing mastectomy in the Fourth Hospital of Hebei Medical University from January 2010 to December 2016 were retrospectively analyzed and 908 cases had complete follow-up data. They were divided into the radiotherapy (RT) group ( n=583) and non radiotherapy (NRT) group ( n=325) according to the radiotherapy. After propensity score matching (PSM) was performed 1 vs. 1, 298 cases were assigned into the RT group and 298 in the NRT group. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using log-rank test. Nomogram prediction model was established, the survival differences were compared among different risk groups, and the radiotherapy benefit populations were screened. Results:Univariate analysis showed that the 5- and 8-year OS and DFS in the RT group were significantly better than those in the NRT group (both P<0.001). Multivariate analysis showed that age, tumor quadrant, number of lymph node metastases, T staging, and Ki-67 level were the independent prognostic factors for OS. Age, tumor quadrant, and T staging were the independent prognostic factors for DFS. The OS nomogram analysis showed that the OS of patients in the high-risk group was significantly improved by post-mastectomy radiotherapy (PMRT) ( P=0.001), while PMRT did not show an advantage in the low- and medium-risk groups ( P=0.057, P=0.099). The DFS nomogram analysis showed that DFS was significantly improved by PMRT in patients in the medium- and high-risk groups ( P=0.036, P=0.001), whereas the benefits from PMRT were not significant in the low-risk group ( P=0.475). Conclusions:For patients with pT 1-2N 1M 0 breast cancer after mastectomy, age ≤ 40 years, tumor located in the inner quadrant or central area, T 2 staging, 2-3 lymph node metastases, Ki-67>30% are the high-risk factors affecting clinical prognosis. The nomogram prediction model can screen the populations that can benefit from PMRT, providing reference for clinical decision-making.

Hepatosteatosis is characterized by abnormal accumulation of triglycerides(TG),leading to prolonged and chronic inflammatory infiltration.To date,there is still a lack of effective and economical therapies for hepatosteatosis.Oridonin(ORI)is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens.In this paper,we showed that ORI exerted significant protective ef-fects against hepatic steatosis,inflammation and fibrosis,which was dependent on LXRα signaling.It is reported that LXRα regulated lipid homeostasis between triglyceride(TG)and phosphatidylethanol-amine(PE)by promoting ATCL and EPT1 expression.Therefore,we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner,and the results showed the TG reduction and PE elevation.In detail,hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATCL and EPT1 genes,respectively.Taken together,the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

Pregnancy ; Female ; Humans ; Placenta ; Nuclear Transfer Techniques ; Embryo, Mammalian ; Cell Nucleus

Objective:To explore the risk factors of early infection patients after heart transplantation(HT)and provide references for preventing and treating early infection.Methods:From April 2018 to May 2021, clinical data were retrospectively reviewed for 95 HT recipients treated at Zhengzhou Seventh People's Hospital.They were divided into two groups of infected(n=34)and uninfected(n=61). Gender, age, disease type, preoperative IABP implantation, postoperative intra-aortic balloon pump(IABP)implantation, postoperative extracorporeal membrane oxygenation(ECMO)implantation, preoperative mechanical ventilation, preoperative leukocyte, preoperative lymphocyte, preoperative serum C-reactive protein(CRP), operative approach, APACHEⅡscore, NYHA grade, hemoglobin, cardiopulmonary bypass time, donor heart cold ischemia time, postoperative thoracic drainage tube indwelling time, postoperative gastric tube indwelling time, postoperative urinary tube indwelling time, postoperative acute rejection, postoperative ventilator assisted treatment time and postoperative ICU time.The risk factors of early infection were analyzed by univariate and multivariate Logistic regression analysis.Results:There were 34 cases of early infection after HT and 8 cases died.In infection group, preoperative hemoglobin(female <110 g/L or male <120 g/L), ECMO post-operation, 24-48 h post-operation, APACHE post-operation(>6), postoperative intrathoracic drainage tube indwelling time(≥7 d), postoperative gastric tube indwelling time(≥4 d), postoperative urinary tube indwelling time(≥5 d), postoperative acute rejection(positive), postoperative ventilator assisted treatment time(≥2 d)and postoperative ICU time(≥10 d)were 18 cases(52.94%), 8(23.53%), 30(88.24%), 22(64.71%), 18(52.94%), 20(58.82%), 4(11.76%), 21(61.76%)and 19(55.88%); uninfected group: 16 cases(26.23%), 3(4.92%), 32(52.46%), 24(39.34%), 15(24.59%), 31(34.43%), 1(1.64%), 21(34.43%)and 4(6.56%). Significant inter-group differences existed( χ2=6.778, 5.68, 12.326, 5.623, 7.740, 5.297, 4.489, 6.615, 28.947, P<0.05). Multivariate Logistic regression analysis indicated that 24-48h post-operation, APACHEⅡ score >6(β=1.024, Wald χ2=7.653, OR=2.141, OR95% CI=1.323~4.215), ECMO post-operation(β=1.783, Wald χ2=6.186, OR=5.949, OR95% CI =1.459~24.25), postoperative intrathoracic drainage tube indwelling time ≥7 d(β=0.712, Wald χ2=5.745, OR=1.054, OR95% CI=1.183~6.753), postoperative gastric tube indwelling time(β=0.832, Wald χ2=6.756, OR=1.132, OR95% CI=1.416~8.406), postoperative ventilator assisted treatment time(β=0.745, Wald χ2=6.563, OR=1.212, OR95% CI=1.289~7.346)and postoperative ICU time=1.28(β=1.325, Wald χ2=9.752, OR=2.435, OR95% CI=1.426~6.354)were independent risk factor for early infection after HT( P<0.05). Conclusions:Early infection after HT remains higher.It is significantly correlated with 24-48 h post-operation APACHE II score, ECMO post-operation, postoperative intrathoracic drainage tube indwelling time, postoperative gastric tube indwelling time, postoperative ventilator assisted treatment time and postoperative ICU time.Targeted interventions should be adopted for lowering the incidence of early infection after HT.

Objective:To observe the clinical evolution process and imaging characteristics of choroidal lesions in different subtypes of serpiginous choroiditis (SC), and to explore the clinical significance of subtype classification.Methods:A retrospective, uncontrolled and observational study. A total of 45 eyes of 25 SC patients diagnosed in Yunnan Eye Hospital from May 2009 to September 2021 were included in the study. According to the initial location of the lesion and fundus images, including fundus color photography, fundus fluorescein angiography (FFA), optical coherence tomography (OCT) and other examination results. SC was divided into peripapillary serpiginous choroiditis, macular serpiginous choroiditis and ampiginous choroiditis. According to the shape of the lesions at the first diagnosis, it can be divided into new lesions with only infiltrating edema, old lesions with only atrophy and recurrent lesions with coexistence of edema and atrophy. the imaging features, development and complications of different subtypes of ocular lesion were observed.Results:Among the 45 eyes of 25 cases, 15 cases were male and 10 cases were female, 20 cases of binocular and 5 cases of monocular, age was 42.3±5.7 years old. There were 21 eyes with active lesions, of which 5 eyes were new lesions and 16 eyes with recurrent lesions; 24 eyes were old lesions. Concurrent optic disc edema occurred in 3 eyes; mild vitreitis occurred in 5 eyes; retinal occurred vasculitis in 3 eyes; choroidal neovascularization occurred in 3 eyes. Among the 16 cases (64%, 16/25) of the peripapillary serpiginous choroiditis, 2 cases (2 eyes) were monocular, and 14 cases (28 eyes) were binocular. Active lesions were found in 16 eyes, of which patients with binocular lesions only one had active lesions. The choroidal lesions that were close to the optic disc or around the optic disc, expanded outwards centrifugally with the prolongation of the disease course, and can progress to the macula. The edge of the lesion was tortuous, with a geographic-like, amoeboid-like and finger-like, polypoid or propeller-like shape. Active lesions in FFA showed weak fluorescence in the early stage and strong fluorescence in the late stage; the old lesions showed weak fluorescence in the early stage and mottled fluorescence in the late stage, and mostly strong fluorescence on the edge. OCT showed thickening of active lesions and thinning of old lesions. Among the 4 cases (16.0%, 4/25) of macular type, 2 cases (2 monocular eyes) had active lesions; 2 cases (4 eyes) had lesion in both eyes, among them, 1 case (2 eyes) had old lesion, and the other case had alternate active lesions. The initial lesions were all located in the off-center of the macula, and most of them were disk-shaped and progressing centrifugally to the periphery. The FFA and OCT imaging findings of the lesions were similar to those of the peridisc type. Among the 5 cases (20.0%, 5/25) of ampiginous choroiditis, 1 case (1 eye) was monocular and 4 cases (8 eyes) were binocular. These lesions were multiple old lesions of varying sizes, gray-white with pigmentation, with clear borders in the posterior pole. Among them 4 eyes have new active lesions appeared near the old lesions. The old lesions showed weak fluorescence with clear borders, and the fluorescein leakage at the late edge formed a strong fluorescence ring; the active lesions showed weak fluorescent spots with blurred edges, and the fluorescence was slightly enhanced in the late stage. In old lesions, atrophy of the photoreceptor layer, RPE and choroid can be seen, and RPE hyperplasia in some areas.Conclusions:SC subtype is a classification of the location of the first lesion, but the characteristics of the repeated attack of this disease can lead to the annihilation of each subtype due to the continuous expansion of the lesion. The phenomenon that the fundus active lesions only occur in one eye that can explain the clinical manifestations of asymmetric morphology of binocular lesions. The characteristics of binocular subtype warn that the predilection site of the healthy eye should be paid attention to.