OBJECTIVE To study the protective effect and potential mechanism of chikusetsu saponin Ⅳ a （chsⅣ） on renal function in diabetic nephropathy （DN） model rats. METHODS DN rat model was established by high-fat diet combined with streptozotocin injection. Thirty-six model rats were randomly divided into model group （i.g. administration of normal saline， high-fat diet）， chsⅣ low-dose and high-dose groups （i.g. administration of 90， 180 mg/kg chsⅣ， high-fat diet）， with 12 rats in each group. Additionally， 10 normal rats were set as the control group （i.g. administration of normal saline， regular diet）. From the 5th to the 12th week after streptozotocin injection， they were given intragastric administration of relevant drug or normal saline， once a day. After the last medication， the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine and urine protein as well as the levels of reduced glutathione （GSH）， superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissues were measured. Additionally， the insulin resistance index was calculated. Hematoxylin-eosin， periodic acid-Schiff， and Masson staining techniques were employed to examine the histopathological alterations in the renal tissue. The expressions of Notch signaling pathway-related proteins in renal tissue were detected by immunohistochemical staining and Western blot methods. RESULTS Compared with model group， the histomorphological of renal tissues in the chsⅣ low- and high-dose groups were significantly improved， with significant decreases in renal histological scores， mesangial expansion index， and glomerulosclerosis scores （ P ＜0.05）； the levels of fasting blood glucose， fasting insulin， blood urea nitrogen， serum creatinine， urine protein and homeostasis model assessment for insulin resistance， as well as MDA content， the expression levels of Notch1， Notch intracellular domain， hairy and enhancer of Split 1 and Delta-like protein 1 in renal tissue were all significantly decreased （ P ＜0.05）. The levels of GSH and SOD in renal tissue were significantly elevated （ P ＜0.05）. Moreover， the improvement in these indicators was significantly more pronounced in the chsⅣ high-dose group compared to the chsⅣ low-dose group （ P ＜0.05）. CONCLUSIONS ChsⅣ can ameliorate renal pathological damage and functional impairment in DN rats. Its underlying mechanisms include restoration of glucose homeostasis and insulin sensitivity， attenuation of renal oxidative stress， and suppression of aberrant Notch signaling pathway activation.

Objective:To detect the levels of sex hormones and insulin in follicular fluid(FF)and the expression level of phosphatase and tensin homolog deleted on chromosome ten(PTEN)in granulosa cells in the infertile patients with polycystic ovary syndrome(PCOS),and to preliminarily explain the correlations between the insulin level and the expression level of PTEN mRNA.Methods:Seventy infertile patients were selected as the subjects and divided into PCOS group and control group(tubal obstruction or infertility due to male factors)according to infertility factors.All patients received in vitro fertilization-embryo transfer(IVF-ET)treatment.FF and ovarian granulosa cells were collected on the day of ovulation.The expression levels of PTEN mRNA in ovarian granulosa cells of the patients in two groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.The levels of sex hormone and insulin in FF were measured by electrochemiluminescence.The correlations of the PTEN mRNA expression level in ovarian granulosa cells and testosterone(T)in FF with the level of insulin in FF were analyzed by Spearman correlation analysis method.Results:There were no significant differences in age,infertility years,body mass index(BMI),basic sex hormone,total dose of gonadotropin(Gn)and days of ovulation induction in two groups(P＞0.05).Compared with control group,the anti-Mullerian hormone(AMH)and antral follicle counting(AFC)of the patients in PCOS group were significantly increased(P＜0.05).The RT-qPCR results showed that the PTEN mRNA expression level in ovarian granulosa cells of the patients in the PCOS group was higher than that in control group(P＜0.001).The electrochemiluminescence results showed that the levels of T and insulin in FF of the patients in PCOS group were higher than those in control group(P＜0.05),whereas the estrogen and progesterone levels were lower than those in control group(P＜0.05).The Spearman correlation analysis showed that that T level in FF was positively correlated with the insulin level of the patients in PCOS group(r=0.577,P＜0.001),and the PTEN mRNA expression level in ovarian granulosa cells was positively correlated with the insulin levels in FF(r=0.616,P＜0.001);in control group,there was no correlation between T level and insulin level in FF(r=0.266,P=0.123),and there was no correlation between the expression level of PTEN mRNA in granulosa cells and the insulin level in FF in control group(r=-0.214,P=0.216).Conclusion:The high expression of PTEN in granulosa cells of the infertile patients with PCOS may be related to the local hyperinsulin level in the ovary,and PTEN participates in the occurrence and development of PCOS.

Objective:Using surface-based morphometry (SBM), this study longitudinally tracks dynamic changes in whole-brain cortical morphological parameters in depression patients before and after vortioxetine treatment. Through three-dimensional topological characterization, we investigate the neuroanatomical correlations between cortical structural reorganization and improvements in affective symptoms and cognitive functions.Methods:Prospectively collected clinical data from 22 outpatients with depression (10 males and 12 females, aged 18-50 years, mean age 28.1±9.1) who attended Beijing Huilongguan Hospital clinic from October 2018 to December 2019. An age-matched healthy control group ( n=21; 10 males and 11 females, aged 22-44 years, mean age 30.8±6.6) was recruited concurrently. The Hamilton Rating Scale for Anxiety (HAMA), the 17-item Hamilton Depression Scale (HAMD 17), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the severity of depressive symptoms and cognitive function in patients. Structural magnetic resonance imaging (sMRI) was performed to assess brain structural indices in depression patients before and after vortioxetine treatment, as well as in healthy controls. Whole-brain cortical structure measurements were calculated for all subjects using CAT12 software. Paired-sample t-tests were used to compare changes in cortical structure and clinical scale scores in depression patients before and after treatment, and two-sample t-tests were conducted to compare whole-brain cortical structure differences between patients (pre-and post-treatment) and healthy controls. Multiple regression analysis in SPM 12 was applied to examine the correlation between post-treatment cortical structural indices and clinical and cognitive scale scores in patients. Spearman correlation analysis was used to evaluate the correlation between changes in whole-brain cortical structure and cognitive function before and after vortioxetine treatment. Results:After vortioxetine treatment, patients with depression exhibited significant reductions in HAMA and HAMD 17 scores, along with significant increases in immediate memory, delayed memory, and total RBANS scores, with statistically significant differences observed ( t=8.43, 12.28, -4.71, -2.41, -3.86 respectively; all P<0.05), while there were no significant changes in visual span, language function, or attention ( P>0.05). Compared to healthy controls, depression patients showed a significantly reduced gyrification index in the right insula/superior temporal gyrus before treatment (28.74±1.20 vs 27.44±1.17; t=4.47, P<0.001), but no significant differences in whole-brain cortical structure were observed before and after treatment or between post-treatment patients and healthy controls ( P>0.05). Correlation analysis indicated that fractal dimension was negatively correlated with HAMA and HAMD 17 scores after treatment, while gyrification index was positively correlated with HAMD 17 ( rpartial=-0.79, -0.83, 0.72; P<0.05). Visual span was positively correlated with fractal dimension ( rpartial=0.78) and negatively correlated with gyrification index ( rpartial=-0.73, P<0.05). Sulcal depth was negatively correlated with attention and RBANS total scores ( rpartial=-0.77, -0.75; P<0.05). Additionally, changes in gyrification index in the left fusiform gyrus were positively correlated with changes in attention ( r=0.51), changes in gyrification index in the left posterior cingulate gyrus were positively correlated with changes in immediate memory ( r=0.58), and changes in sulcal depth in the left superior frontal gyrus were negatively correlated with changes in language ability ( r=-0.79) (both P<0.05). Conclusion:Vortioxetine treatment can improve anxiety and depressive symptoms in depression patients, as well as enhance certain cognitive functions, while also affecting cortical structure in the specific cortical area. Changes in cortical structure after vortioxetine treatment are closely related to clinical symptom improvement and cognitive function changes.

Objective:To explore the relationship between medical students'family function and anxiety/depression,and the mediating role of loneliness in this relationship.Methods:A total of 577 medical students were surveyed using stratified cluster sampling.Questionnaires assessed family function,loneliness,anxiety,and depression.Spearman correlation analysis was used to examine the relationships among family function,loneliness,anxiety,and depression.The mediating effects were tested using SPSS 26.0 PROCESS program model 4.Results:Medical students'family function,loneliness,anxiety,and depression scores were 8.00(5.00,10.00),16.00(12.00,19.00),3.00(2.00,4.00),and 3.00(2.00,4.00),respectively.Spearman correlation analysis showed that family function was negatively correlated with loneliness(r=-0.337),anxiety(r=-0.237),and depression(r=-0.257)(all P＜0.01).Loneliness was positively correlated with anxiety(r=0.394)and depression(r=0.392)(both P＜0.01).Anxiety was positively correlated with depression(r=0.746,P＜0.01).Family function negatively predicted anxiety(β=-0.118,P＜0.01),depression(β=-0.105,P＜0.01),and loneliness(β=-0.322,P＜0.01).Loneliness positively predicted anxiety(β=0.348,P＜0.01)and depression(β=0.346,P＜0.01).Loneliness played a partial mediating role in the relationship of family function with anxiety and depression among medical students,with mediating effects of 49.0%and 43.2%,respectively.Conclusions:Family function not only directly affects medical students'anxiety and depression but also indirectly affects them by influencing loneliness.Therefore,improving medical students'family function can effectively reduce their loneliness,thereby helping to alleviate anxiety and depression.

Objective:To analyze the genetic characteristics of the prevalent strains of Varicella-Zoster virus (VZV) in the population of Dali, Yunnan, and to understand its evolutionary status in the population of Dali.Methods:Herpes fluid and 163 sera were collected from 249 patients clinically suspected to have varicella or herpes zoster in the Department of Dermatology of the Second People′s Hospital of Dali city, Yunnan province, China, from 2023 to 2024. The levels of VZV-specific IgG and IgM antibodies in serum were detected using enzyme-linked immunoassay. Viral DNA was extracted from the herpes fluid, and the cycle threshold ( Ct) of the samples was detected using quantitative real-time polymerase chain reaction (qPCR), and some samples with Ct ≦ 22 were selected for sequencing by next-generation sequencing technology (next-generation sequencing). Next-generation sequencing (NGS) was used to obtain 90 whole genome sequences of VZV, and the sequencing result were compared with the sequences of reference strains for multiple sequence comparison and evolutionary analysis. Snapgene was used to translate the nucleotides into amino acids, and the result were compared with the amino acid sequences of the reference strain. Results:Of the 90 VZV whole-genome sequences, one whole-genome sequence was from an adult varicella patient, and the remaining 89 whole-genome sequences were from herpes zoster patients. The serum-specific IgG antibody positivity rate was 99.4%, and the IgM antibody positivity rate was 52.8%. The result of both single nucleotide polymorphism (SNPs) site typing and genome-wide phylogenetic tree analysis showed that 83 of the 90 VZV whole-genome sequences in this study were on the same branch as Clade 2, and 7 VZV whole-genome sequences were on the branch of Clade 9.Conclusions:The main endemic branch in Dali region in 2023-2024 was Clade 2, with the emergence of Clade 9 branch; there were amino acid mutations in the proteins encoded by ORF22 and ORF68 in 83 VZV whole genome sequences of Clade 2 branch, and the mutations did not cause significant changes to the protein structure.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective:To evaluate the effect of transient receptor potential vanilloid type 1 (TRPV1) gene polymorphism on the postoperative analgesic efficacy of alfentanil in patients undergoing radical mastectomy.Methods:In this prospective study, adult female patients diagnosed with breast cancer who underwent surgical treatment at the First Affiliated Hospital of Zhengzhou University were selected as case group ( n=162), while age-matched healthy adult females were selected as control group ( n=80). All subjects had a body mass index of 18-30 kg/m 2. The genotype and allele frequencies of TRPV1 rs8065080 and rs222747 were compared between the two groups, and the consumption of alfentanil and requirement for rescue analgesia within 48 h after surgery were recorded in breast cancer patients with different TRPV1 rs222747 genotypes. Results:Three genotypes of CC, GC, and GG were detected at rs222747 locus of TRPV1 gene, and there was no significant difference in the genotype distribution between the two groups ( P>0.05). Three genotypes of CC, TC and TT were detected at rs8065080 locus of TRPV1 gene, and there was significant difference in the genotype distribution between the two groups ( P<0.05). There was no significant difference in the basic data of patients with different genotypes of TRPV1 gene rs222747 locus ( P>0.05). There were significant differences in the consumption of alfentanil during 0-24 h after surgery and during 24-48 h after surgery and rate of rescue analgesia within 48 h after surgery among patients with different genotypes of TRPV1 gene rs222747 locus ( P<0.05). Conclusions:The polymorphism at the TRPV1 gene rs222747 locus can influence the postoperative analgesic efficacy of alfentanil in breast cancer patients undergoing radical mastectomy, suggesting that genetic factors may be one of the reasons for the inter-individual variability in alfentanil efficacy.

Objective To observe the value of artificial intelligence iterative reconstruction(AIIR)for low-dose chest CT images of infants with congenital heart disease.Methods Totally 262 infants with congenital heart disease who would undergo chest CT scanning were prospectively enrolled and randomly divided into low-dose group(n=142)and conventional dose group(n=120).Chest CT scanning with tube voltage of 80 kVp and tube current of 10 mAs was performed in low-dose group,and hybrid iterative reconstruction(HIR,group A)and AIIR(group B)were used to reconstruct images,respectively.In conventional dose group,chest CT scanning with tube voltage of 80 kVp and tube current of 100 mAs was performed,and HIR was used to reconstruct images(group C).Then subjective and objective evaluation on image quality were performed,the results were compared among 3 groups,and the value of AIIR was analyzed.Results Significant differences of image quality and clarity of displaying structures were found among 3 groups(all P＜0.001).Among them,except for the clarity of interlobar fissure,no significant difference of subjective scores was found between low-dose AIIR images and conventional dose HIR images(all corrected P＞0.05),while subjective scores of low-dose HIR images were all lower than those of low-dose AIIR images and conventional dose HIR images(all corrected P＜0.05).Significant differences of standard deviation(SD),signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)were found among 3 groups(all P＜0.001)and between each 2 groups(all corrected P＜0.05).The effective dose of low-dose group and conventional dose group was 0.09(0.08,0.10)and 0.85(0.75,1.03)mSv,respectively,and the former was lower than the latter(Z=-13.942,P＜0.001).Conclusion Using AIIR could obtain low-dose chest CT images of infants with quality comparable to conventional chest CT images.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective:To analyze the impact of different intrauterine intervention methods and types of complications on fetal prognosis in cases of giant placental chorioangioma (CA), and determine the indications for various treatment methods by analyzing cases of adverse outcomes.Methods:Relevant articles were retrieved from China National Knowledge Infrastructure, VIP Database, Wanfang Database, and Yiigle using the keywords "placental chorioangioma" and "fetal edema" or "anemia" or "cardiomegaly" or "polyhydramnios," and from PubMed, Embase, and UpToDate databases using the keywords "placental chorionic angioma or chorioangioma" and "fetal edema" or "anemia" or "polyhydramnios" or "hyperdynamic circulation" up to June 30th 2023. The size of the angiomas, fetal complications, intrauterine intervention methods, gestational weeks at intervention, and pregnancy outcomes were analyzed. Fetal and neonatal deaths were defined as adverse outcomes. Statistical analysis was performed using an independent sample t-test, rank-sum test, or Chi-square test (continuity correction Chi-square test or Pearson Chi-square test). Results:(1) A total of 582 articles were retrieved, and 51 articles were finally included, comprising 65 cases. Based on the intrauterine intervention methods, these cases were divided into the symptomatic treatment group (17 cases) and the etiological treatment group (48 cases). There were no statistically significant differences between the two groups in the maximum diameter of the angiomas, the gestational weeks at intervention, or the gestational weeks at delivery. (2) The incidence of adverse outcomes was 3/17 in the symptomatic treatment group and 27.1% (13/48) in the etiological treatment group, with no statistically significant difference. In the etiological treatment group, the incidence of adverse outcomes in cases with fetal edema was 45.4% (10/22), which was significantly higher than the 11.5% (3/26) in cases without fetal edema, and the difference was statistically significant ( χ 2=6.94, P=0.008). (3) An analysis of 13 cases with adverse outcomes revealed that nine cases had highly vascularized chorioangiomas and/or blood supply vessels located close to the umbilical cord insertion point on the placenta, and nine were complicated by fetal edema. The incidence of adverse outcomes for fetoscopic laser coagulation/bipolar coagulation, radiofrequency or microwave ablation, bioglue embolization, anhydrous alcohol ablation, and microcoil embolization were 4/19, 3/4, 1/8, 2/9, and 3/6, respectively. Conclusions:Intrauterine treatment of CA should be individualized. Bioglue embolization may be the first-line treatment; Fetoscopic laser coagulation can be applied to cases where the blood supply vessels are small and superficial;Interstitial laser ablation and radiofrequency ablation can be used for branch-type CA when the main blood supply vessels are located within the hemangioma; Anhydrous alcohol ablation is contraindicated due to its risk of fetal circulation entry; Microcoil embolization has the risk of incomplete occlusion, which should be used with caution.