ObjectiveTo construct and validate a clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure （CHF），aiming to assist clinical diagnosis and provide tools and methods for individualized treatment of CHF. MethodsThe clinical data of patients with chronic heart failure treated at Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2022 to January 2024 were retrospectively collected. The patients were randomly divided into a training group and a validation group with a ratio of 7∶3. First， the least absolute shrinkage and selection operator （LASSO） regression analysis was used to preliminarily screen the predictive factors affecting the diagnosis of Qi deficiency and blood stasis syndrome in CHF. Subsequently， the Logistic regression method was applied to conduct a more in-depth and detailed analysis of these factors. Variables with P<0.05 in the results of the multi-factor Logistic regression were carefully selected and included. Based on the regression coefficients obtained from this analysis， a model was constructed， and a nomogram was accurately drawn. Using R software，the receiver operating characteristic （ROC） curve，calibration curve，and decision curve analysis （DCA） were precisely drawn. These analyses were used to comprehensively evaluate the model from three crucial aspects： discrimination，calibration，and clinical applicability. Additionally， the accuracy，specificity，sensitivity，positive predictive value，and negative predictive value of the model were meticulously calculated to conduct a more all-round and comprehensive assessment. ResultsIn total， 168 cases were successfully obtained in the training group， and 71 cases were included in the validation group. After a thorough comparison， it was found that there were no statistically significant differences in the baseline data between the two groups. After being rigorously screened by the LASSO-multivariate logistic regression method， dark red tongue，smoking history，cardiac troponin I，and N-terminal pro-B-type natriuretic peptide （NT-ProBNP） were identified as the influencing factors for diagnosing patients with the Qi deficiency and blood stasis syndrome in CHF. The constructed model demonstrated an area under the curve （AUC） of 0.812 in the training group and 0.719 in the validation group. The calibration curve showed that the predicted curve of the model was close to the actual observed curve. DCA indicated that the model could provide substantial clinical benefits for patients at the decision thresholds ranging from 0.2 to 0.9. ConclusionThe clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure constructed in this study shows good performance. It has certain application value in clinical practice， which may contribute to the improvement of the diagnosis and treatment of CHF patients with this syndrome.

Objective : To explore the association between serum γ-aminobutyric acid ( GABA) levels and the risk of developing type 2 diabetes( T2DM) ． Methods : 187 cases of T2DM patients attending the hospital were selected as the T2DM group，and 187 cases of non-T2DM population attending the same period of time were selected as the control group according to age ( ± 3 years) and gender 1 ∶ 1．On-site questionnaires and physical examination were conducted for the study subjects，and serum levels of GABA，Malondialdehyde ( MDA) and activities of superoxide dismutase ( SOD) and Glutathione peroxidase ( GSH-Px) were detected by using ELISA kits．The differences in the levels of GABA and oxidative stress indicators ( SOD，GSH-Px，MDA) between the two groups were compared， and the correlation between GABA and oxidative stress indicators was analyzed by Spearman's method; GABA and oxidative stress indicators were divided into three groups according to their control quartiles，respectively ［low level group ( Q1: ＜P25) ，medium level group ( Q2: P25 －P75) ，high level group ( Q3: ＞P75) ］，and conditional logistic regression was applied to analyze the relationship between GABA，oxidative stress indicators and the risk of develo- ping T2DM; the dose-response relationship between GABA，oxidative stress indicators and the risk of developing T2DM was analyzed by using restricted cubic spline ( RCS) ． Results : T2DM group ( P＜0. 05) ．Spearman's correlation analysis showed that GABA level was positively correlated with SOD and GSH-Px activities and negatively correlated with MDA level ( P＜0. 001) ．Conditional logistic regression analysis showed that medium levels of SOD and GSH-Px as well as medium and high levels of GABA were protective factors for T2DM compared with low levels in each group ( P＜0. 05) ．RCS results showed that a negative dose-response relationship between GABA，GSH-Px and the risk of developing T2DM，and SOD showed a trend of decreasing and then increasing the risk of developing T2DM ( P＜0. 05) ． Conclusion Serum GABA levels have been associated with the risk of developing T2DM．As serum GABA levels increase，the risk of developing T2DM may decrease．

Objective To investigate the value of CT radiomics for predicting effect of neoadjuvant chemotherapy(NACT)for locally advanced gastric cancer(LAGC).Methods Totally 325 LAGC patients who received NACT were retrospectively enrolled,among them 247 were taken as training set,while the rest 78 were taken as validation set.Tumor regression scale(TRG)was evaluated according to postoperation pathology after NACT,and the efficacy of NACT was evaluated.Univariate logistic regression was used to analyze and screen clinical predictors of effect of NACT,and clinical model was constructed.Radiomics features were extracted based on venous phase enhanced CT pre-and post-NACT,and Delta radiomics features(i.e.the ratio of the difference of pre-and post-NACT radiomics features and pre-NACT radiomics features)were calculated.The best features were screened based on pre-NACT,post-NACT and Delta radiomics features to construct radiomics labels,the optimal label was screened and used to construct combined model through combining clinical model.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate predicting efficiency of the above models.Decision curve analysis(DCA)was performed to explore the clinical value of each model.Results In training set,significant effect was found in 67 cases,but not in 180 cases,while in validation set,significant effect was found in 18 cases but not in 60 cases.Borrmann classification of LAGC before NACT was the clinical predictor(P=0.031),and clinical model was constructed,which had AUC of 0.577 and 0.520 in training and validation sets,respectively.Based on pre-NACT,post-NACT and Delta radiomics features,19,14 and 17 best features were selected,and AUC of the established radiomics labels of Pre-Rad,Post-Rad and Delta-Rad in training set was 0.672,0.796 and 0.789,while in validation set was 0.558,0.805 and 0.666,respectively.Post-Rad was the optimal label,which was used to construct combined model.AUC of the obtained combined model in training and validation sets was 0.824 and 0.818,respectively,both higher than that of clinical model(both P＜0.001)but not different with that of Post-Rad(both P＞0.05).Taken 0.4 to 0.7 as the threshold,the combined model had higher clinical net benefit than the other two.Conclusion Venous CT radiomics could effectively predict effect of NACT for LAGC.Combining with clinical features could improve its predictive efficacy.

This study analyzed the clinical and laboratory data of 3 children diagnosed with mitochondrial disease-associated primary adrenal insufficiency (PAI) at the Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from October 2018 to November 2023.All patients were normal at birth but gradually developed symptoms and were diagnosed with PAI between the ages of 1 year and 1 month and 7 years and 3 months.The children presented typical clinical symptoms of PAI, including skin and mucosal hyperpigmentation (3 cases), electrolyte disturbances (3 cases), and hypoglycemia (2 cases), as well as multisystem abnormalities related to mitochondrial disease, including recurrent infections, growth retardation, cachexia, and hyperlactatemia.Genetic testing revealed significant single deletions in mitochondrial DNA in all patients: Patient 1: m.11219_15954del, Patient 2: m.8483_13459del, and Patient 3: m.8649_16084del.Treatment with Hydrocortisone acetate replacement therapy improved the electrolyte disturbances and hypoglycemia, but issues with recurrent infections, growth retardation, and cachexia persisted.This study suggests that in clinical practice, the possibility of mitochondrial disease should be highly suspected when PAI patients present with multisystem abnormalities, especially in conjunction with hyperlactatemia.

Objective To investigate the value of CT radiomics for predicting effect of neoadjuvant chemotherapy(NACT)for locally advanced gastric cancer(LAGC).Methods Totally 325 LAGC patients who received NACT were retrospectively enrolled,among them 247 were taken as training set,while the rest 78 were taken as validation set.Tumor regression scale(TRG)was evaluated according to postoperation pathology after NACT,and the efficacy of NACT was evaluated.Univariate logistic regression was used to analyze and screen clinical predictors of effect of NACT,and clinical model was constructed.Radiomics features were extracted based on venous phase enhanced CT pre-and post-NACT,and Delta radiomics features(i.e.the ratio of the difference of pre-and post-NACT radiomics features and pre-NACT radiomics features)were calculated.The best features were screened based on pre-NACT,post-NACT and Delta radiomics features to construct radiomics labels,the optimal label was screened and used to construct combined model through combining clinical model.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate predicting efficiency of the above models.Decision curve analysis(DCA)was performed to explore the clinical value of each model.Results In training set,significant effect was found in 67 cases,but not in 180 cases,while in validation set,significant effect was found in 18 cases but not in 60 cases.Borrmann classification of LAGC before NACT was the clinical predictor(P=0.031),and clinical model was constructed,which had AUC of 0.577 and 0.520 in training and validation sets,respectively.Based on pre-NACT,post-NACT and Delta radiomics features,19,14 and 17 best features were selected,and AUC of the established radiomics labels of Pre-Rad,Post-Rad and Delta-Rad in training set was 0.672,0.796 and 0.789,while in validation set was 0.558,0.805 and 0.666,respectively.Post-Rad was the optimal label,which was used to construct combined model.AUC of the obtained combined model in training and validation sets was 0.824 and 0.818,respectively,both higher than that of clinical model(both P＜0.001)but not different with that of Post-Rad(both P＞0.05).Taken 0.4 to 0.7 as the threshold,the combined model had higher clinical net benefit than the other two.Conclusion Venous CT radiomics could effectively predict effect of NACT for LAGC.Combining with clinical features could improve its predictive efficacy.

This study analyzed the clinical and laboratory data of 3 children diagnosed with mitochondrial disease-associated primary adrenal insufficiency (PAI) at the Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from October 2018 to November 2023.All patients were normal at birth but gradually developed symptoms and were diagnosed with PAI between the ages of 1 year and 1 month and 7 years and 3 months.The children presented typical clinical symptoms of PAI, including skin and mucosal hyperpigmentation (3 cases), electrolyte disturbances (3 cases), and hypoglycemia (2 cases), as well as multisystem abnormalities related to mitochondrial disease, including recurrent infections, growth retardation, cachexia, and hyperlactatemia.Genetic testing revealed significant single deletions in mitochondrial DNA in all patients: Patient 1: m.11219_15954del, Patient 2: m.8483_13459del, and Patient 3: m.8649_16084del.Treatment with Hydrocortisone acetate replacement therapy improved the electrolyte disturbances and hypoglycemia, but issues with recurrent infections, growth retardation, and cachexia persisted.This study suggests that in clinical practice, the possibility of mitochondrial disease should be highly suspected when PAI patients present with multisystem abnormalities, especially in conjunction with hyperlactatemia.

Objective:To analyze the safety and efficacy of PD-1 inhibitors versus chemotherapy or ipilimumab in advanced melanoma.Methods:PubMed,CNKI,VIP and Wanfang databases were searched to collect randomised controlled trials of PD-1 inhibi-tors in treatment of advanced melanoma.The search time was from the establishment of the database to May 1,2022.Two reviewers independently screened the literature,extracted data,and assessed risk of bias of included studies.Meta-analysis was performed using RevMan5.4 and STATA16 software.Results:A total of 7 studies were included.Meta-analysis results show that:①Safety:Compared with chemotherapy,PD-1 inhibitor treatment had fewer adverse events,especially in the blood system;compared with ipilimumab alone,PD-1 inhibitor combined with ipilimumab had more adverse events,especially liver function indicators;there was no signifi-cant difference in the incidence of total adverse events between PD-1 inhibitor monotherapy and ipilimumab monotherapy.②Efficacy:The PFS,OS and ORR of PD-1 inhibitor versus chemotherapy or ipilimumab were HR=0.54,95%CI(0.45,0.62),P<0.05,HR= 0.69,95%CI(0.58,0.80),P=0.03 and OR=3.16,95%CI(2.59,3.86),P<0.05,respectively.Conclusion:PD-1 inhibitors have good efficacy in treatment of advanced melanoma,while different combination methods and different control treatments may have different efficacy.Limited by the quantity and quality of included studies,more research evidence is needed to support this.

Objective:To design and evaluate the application value of intracavitary-interstitial brachytherapy (IC-ISBT) applicator template for locally advanced cervical cancer.Methods:MRI data of 100 patients with ⅡB-ⅣA stage cervical cancer (International Federation of Gynecology and Obstetrics 2018 staging system) before and after external beam radiation therapy (EBRT) admitted to Sun Yat-sen University Cancer Center from March 2019 to September 2020 were collected. The range of primary cervical lesions was retrospectively analyzed and compared. Based on the residual mass of patients, the corresponding high-risk clinical target volume (HR-CTV) was delineated, and the IC-ISBT applicator template was designed and initially applied to cervical cancer patients. Dosimetry analysis and efficacy evaluation were compared between the applicator template-guided ( n=37) and free-hand implantation groups ( n=63). Chi-square test or Fisher exact test was performed for categorical variables, and t-test or U-test for continuous variables. Results:The median distance between the residual tumor margin (clockwise 3, 6, 9, 12 o'clock) and the center of 100 patients with ⅡB-ⅣA stage cervical cancer after EBRT was 16.5, 14.0, 17.0 and 13.0 mm, respectively. The corresponding HR-CTV was superimposed to reconstruct the three-dimensional diagram, and the cylindrical IC-ISBT applicator template with mushroom-like head was designed and manufactured: the longest and shortest diameter of the head was 35 and 20 mm, respectively; the central channel was adapted to the uterine tube, the C1-C12 channels was arranged in inner circle, and the peripheral B1-B5 and A1-A4 pin channels were expanded bilaterally. In terms of dose coverage, there was no significant difference between the HR-CTV D 90% [(635.12±22.65) vs. (635.80±25.84) cGy], bladder D 2 cm3 [(473.79±44.78) vs. (463.55±66.43) cGy)], rectum D 2 cm3 [(396.99±73.54) vs. (408.00±73.94) cGy] and sigmoid colon D 2 cm3 [(293.07±152.72) vs. (311.31±135.77) cGy] between the template-guided and free-hand implantation groups (all P>0.05), but the HR-CTV D 98% was significantly higher [(544.78±32.07) vs. (536.78±32.04) cGy, P=0.007] and the rectum D 1 cm3 and D 0.1 cm3 were significantly lower [(438.62±69.65) vs. (453.97±67.89) cGy, P=0.016; (519.46±70.67) vs. (543.82±81.24) cGy, P=0.001] in the template-guided implantation group. In addition, there was no significant difference in the complete response rate between two groups (86% vs. 83%, P>0.05). Conclusions:This IC-ISBT applicator template is reasonably designed, and the therapeutic efficacy of the template-guided implantation is equivalent to that of free-hand implantation. The dose coverage of the target area meets the clinical demand with a better protection of the organs at risk. The applicator template has the potential to be widely used as a conventional template in clinical practice as the applicator-guided implantation is convenient to operate and repeat.

Objective:To explore the effect and mechanism of c-Myc on regulating the expression of immune-related ligands in Y subtype small-cell lung cancer (SCLC) characterized by high expression of immune-related molecules.Methods:The Y subtype SCLC cell line H196 was randomly divided into the control group, c-Myc inhibitor 10058-F4 group, histone deacetylase 1 (HDAC1) inhibitor pyroxamide group, and 10058-F4 plus pyroxamide group. The co-culture system with NK-92MI cells was used to determine the effect of H196 cells on the function of natural killer (NK) cells. Western Blotting and co-immunoprecipitation assays were used to detect the effect of c-Myc on class Ⅰ HDAC, and flow cytometry was used to detect the regulatory effect of c-Mycon CD47, programmed cell death ligand 1 (PD-L1), and CD155, which are highly expressed immune checkpoints in Y subtype SCLC, and major histocompatibility complex classⅠ-related chains A and (MICA/B), which is a poorly expressed immune-activating ligand in SCLC, and the role of HDAC. Chromatin immunoprecipitation (ChIP) assay and real-time quantitative polymerase chain reaction (RT-qPCR) were used to determine the regulatory mechanism of c-Myc-HDAC1 on MICA/B expression.Results:Inhibition of c-Myc decreased the mortality of H196 cells in the co-culture system and down-regulated the expression of MICA/B. Compared with the NK+H196 group [(42.54±2.47)%], the proportion of cells killed by NK-92MI cells in the NK+H196+10058-F4 group was lower [(28.48±3.38)%, P＜0.001]. The mean fluorescence intensity (MFI) of MICA/B on the cells in the 10058-F4 group (36.40±0.82) was lower than that in the control group (91.23±8.60, P＜0.001). And c-Myc could bind to HDAC1, whose protein level was up-regulated by 10058-F4 while the mRNA level was not. Compared with the cells in the control group (90.10±4.91), the MFI of MICA/B on the cells in the pyroxamide group was significantly increased (145.70±5.86, P＜0.001), and the MFI of MICA/B on the cells in the 10058-F4+pyroxamide group (54.60±2.88) was significantly increased compared with the cells in the 10058-F4 group (35.97±1.60, P＜0.001). The percentage of MICA promoter gene fragments in the c-Myc antibody precipitation group (0.125±0.037) was significantly higher than that in the IgG group (0.000 8±0.000 3, P=0.004). MICB had a similar trend, suggesting that the c-Myc-HDAC1 complex could bind to the promoter region of MICA/B. The MFI of CD47 on the cells in the 10058-F4 group (60.07±0.21) was significantly lower than cells in the control group (70.27±1.37, P＜0.001), but the MFIs of PD-L1 (13.50±0.61) and CD155 (829.70±41.19) were significantly higher than those on the cells in the control group (9.23±0.94, P＜0.01; 496.00±4.36, P＜0.001, respectively). Conclusions:c-Myc may promote the expression of MICA/B and CD47 in Y subtype SCLC cells by binding and inhibiting HDAC1, while it may also be involved in inhibiting the expression of PD-L1 and CD155 in SCLC cells.

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.