ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

OBJECTIVE: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. METHODS: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. RESULTS: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1)-mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. CONCLUSION This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolism-related diseases.

Objective:To investigate the influence of genetic and environmental factors on the clinical characteristics of upper urinary tract calculi in pediatric patients.Methods:This study was a retrospective case series. The clinical data of 179 children under the age of 14 with upper urinary tract calculi treated at Beijing Friendship Hospital，Capital Medical University，from August 2014 to February 2023 were analyzed. There were 121 males（67.60%）and 58 females（32.40%），with a median age at onset of 2.10（1.14，5.17）years. Thirty-three cases（18.44%）had a family history of urinary stone disease. Stone characteristics was defined by CT，with a median stone burden（sum of the diameters of all stones）of 1.3（1.00，1.60）cm. Fifty-four（30.17%）children had staghorn calculi. Multiple stones were present in 92 cases（51.40%），and bilateral stones in 52 cases（29.05%），with hydronephrosis was present in 119 children（66.48%）. The median follow-up time was 67 months，and 36 children（20.11%）experienced stone recurrence. Dietary habits and related information were collected by electronic questionnaire，including a total of 115 children（64.25%）with an unbalanced diet，101（56.42%）with insufficient water intake，and 32 children（17.88%）with a preference for a high-protein diet. Tap water was used as the source of drinking water by 128 patients（71.51%），and 107（59.78%）took dietary supplements. Whole-exome sequencing revealed that 55 children（30.73%）carried pathogenic mutations in stone-related genes. Binary logistic regression was used for univariate analysis of above risk factors. Variables with P < 0.1 in univariate analysis and without multicollinearity were included in multivariate logistic regression to further screen for independent risk factors. Results:Multivariate analysis confirmed that carrying stone-related pathogenic gene mutations（ OR = 3.06，95% CI 1.25?7.45， P = 0.014）and insufficient water intake（ OR = 3.28，95% CI 1.14?9.47， P = 0.028）were independent risk factors for higher stone burden. A high-protein diet（ OR = 2.40，95% CI 1.03?5.63， P = 0.044），carrying stone-related pathogenic gene mutations（ OR = 4.57，95% CI 2.21?9.46， P<0.01），and a family history of stones（ OR = 3.18，95% CI 1.28 ~ 7.91， P = 0.013）were independent risk factors for staghorn calculi. Multiple stones were closely associated with a family history of stones（ OR = 2.66，95% CI 1.15-6.17， P = 0.022）and carrying stone-related pathogenic gene mutations（ OR = 3.22，95% CI 1.60-6.48， P = 0.001）. Moreover，carrying stone-related pathogenic gene mutations（ OR = 5.19，95% CI 2.52?13.82， P < 0.01）were an independent risk factor for stone recurrence，whereas dietary supplement intake was a protective factor（ OR = 0.26，95% CI 0.11?0.62， P = 0.002）. Conclusions:Genetic and environmental factors play significant roles in the occurrence and development of pediatric upper urinary tract stones. A high-protein diet as well as a positive family history of stones are independent risk factors for staghorn calculi，and insufficient water intake is a critical environmental factor for stone formation，while appropriate use of dietary supplements may help reduce the risk of stone recurrence. Genetic testing indicates that approximately 30% of children carry stone-related pathogenic gene mutations，and these patients prone to severe stone and an increased risk of recurrence.

Objective:To investigate the risk factors for detecting clinically significant prostate cancer (CSPCa) in patients with Prostate Imaging Reporting and Data System (PI-RADS) score≤3 on multi-parameter magnetic resonance imaging (mpMRI).Methods:Retrospective analysis was performed on the case data of 335 patients with suspected prostate cancer and PI-RADS score ≤3 who were admitted to Beijing Friendship Hospital, Capital Medical University from January 2013 to October 2022. All patients underwent 24-needle prostate biopsy. Clinical data such as age, body mass index, past medical history, serological laboratory indicators, and mpMRI imaging data were collected. The patients were grouped according to whether the puncture pathology was CSPCa or not, and the differences in clinical data between the two groups were analyzed by t-test, rank sum test and Chi-test. Multivariate Logistic regression analysis was further used to determine independent risk factors for MRI invisible prostate cancer, and receiver operating characteristics (ROC) curves were drawn. At the same time, further subgroup analysis was conducted based on whether prostate-specific antigen (PSA) was positive before puncture and PI-RADS score, respectively, and the same statistical method was used to further determine the influence of different serological indicators and PI-RADS score on the analysis results of risk factors. Results:Among all patients, 81 were CSPCa patients and 254 were non-CSPCa patients. Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) and PI-RADS score of 3 were independent risk factors for MRI invisible prostate cancer. At the same time, compared with suspected lesions located only in the transitional zone, the incidence of CSPCa in patients with suspected lesions located in the peripheral zone would increase, and the incidence of CSPCa would further increase when suspected lesions were found in both the transitional zone and the peripheral zone. In PSA-negative patients, only suspected lesion location was an independent risk factor for MRI invisible prostate cancer, while in PSA-positive patients, prostate volume, PSAD, and PI-RADS scores were independent risk factors. In subgroup analysis with different PI-RADS scores, suspicious lesions in both the transitional zone and peripheral zone indicate a higher likelihood of CSPCa. For patients with PI-RADS scores of 1 to 2, suspicious lesions in the peripheral zone alone may also indicated CSPCa, while for patients with PI-RADS scores of 3, the lower free prostate-specific antigen/total prostate-specific anti-principle was more accurate in predicting CSPCa.Conclusions:For patients who are clinically suspected of prostate cancer but whose PI-RADS score is less than or equal to 3 points indicated by mpMRI, it is necessary to further focus on the results of different serological indicators according to whether their PSA is positive and PI-RADS score respectively to judge whether patients should receive systemic prostate puncture, instead of using PSA level as a single indication for puncture. At the same time, clinicians should also pay full attention to the location of suspected lesions, when they are located in the peripheral zone, or there are suspected lesions in both the peripheral zone and the transitional zone, the possibility of CSPCa should be fully considered.

Objective:To investigate the influence of genetic and environmental factors on the clinical characteristics of upper urinary tract calculi in pediatric patients.Methods:This study was a retrospective case series. The clinical data of 179 children under the age of 14 with upper urinary tract calculi treated at Beijing Friendship Hospital，Capital Medical University，from August 2014 to February 2023 were analyzed. There were 121 males（67.60%）and 58 females（32.40%），with a median age at onset of 2.10（1.14，5.17）years. Thirty-three cases（18.44%）had a family history of urinary stone disease. Stone characteristics was defined by CT，with a median stone burden（sum of the diameters of all stones）of 1.3（1.00，1.60）cm. Fifty-four（30.17%）children had staghorn calculi. Multiple stones were present in 92 cases（51.40%），and bilateral stones in 52 cases（29.05%），with hydronephrosis was present in 119 children（66.48%）. The median follow-up time was 67 months，and 36 children（20.11%）experienced stone recurrence. Dietary habits and related information were collected by electronic questionnaire，including a total of 115 children（64.25%）with an unbalanced diet，101（56.42%）with insufficient water intake，and 32 children（17.88%）with a preference for a high-protein diet. Tap water was used as the source of drinking water by 128 patients（71.51%），and 107（59.78%）took dietary supplements. Whole-exome sequencing revealed that 55 children（30.73%）carried pathogenic mutations in stone-related genes. Binary logistic regression was used for univariate analysis of above risk factors. Variables with P < 0.1 in univariate analysis and without multicollinearity were included in multivariate logistic regression to further screen for independent risk factors. Results:Multivariate analysis confirmed that carrying stone-related pathogenic gene mutations（ OR = 3.06，95% CI 1.25?7.45， P = 0.014）and insufficient water intake（ OR = 3.28，95% CI 1.14?9.47， P = 0.028）were independent risk factors for higher stone burden. A high-protein diet（ OR = 2.40，95% CI 1.03?5.63， P = 0.044），carrying stone-related pathogenic gene mutations（ OR = 4.57，95% CI 2.21?9.46， P<0.01），and a family history of stones（ OR = 3.18，95% CI 1.28 ~ 7.91， P = 0.013）were independent risk factors for staghorn calculi. Multiple stones were closely associated with a family history of stones（ OR = 2.66，95% CI 1.15-6.17， P = 0.022）and carrying stone-related pathogenic gene mutations（ OR = 3.22，95% CI 1.60-6.48， P = 0.001）. Moreover，carrying stone-related pathogenic gene mutations（ OR = 5.19，95% CI 2.52?13.82， P < 0.01）were an independent risk factor for stone recurrence，whereas dietary supplement intake was a protective factor（ OR = 0.26，95% CI 0.11?0.62， P = 0.002）. Conclusions:Genetic and environmental factors play significant roles in the occurrence and development of pediatric upper urinary tract stones. A high-protein diet as well as a positive family history of stones are independent risk factors for staghorn calculi，and insufficient water intake is a critical environmental factor for stone formation，while appropriate use of dietary supplements may help reduce the risk of stone recurrence. Genetic testing indicates that approximately 30% of children carry stone-related pathogenic gene mutations，and these patients prone to severe stone and an increased risk of recurrence.

Objective:To analyse the differences of related genes between serum alpha-fetoprotein (AFP) positive gastric cancer and AFP negative gastric cancer, and the relationship between related genes and prognosis of serum AFP positive gastric cancer.Methods:A total of 1 144 gastric cancer patients undergoing surgery at the 940th Hospital , Joint Logistic Support Force, People's Liberation Army from Jan 2013 to Dec 2018 were retrospectively analyzed. Of them, 47 cases were of AFP positive gastric cancer, and 47 serum AFP negative case were obtained by proper matching method.Results:Forty-seven patients with serum AFP positive gastric cancer, accounting for 4.1% of all gastric cancer patients during the same period. The prognosis of serum AFP negative gastric cancer is better than that of serum AFP positive gastric cancer. The 1-, 3- and 5-year cumulative survival rates were 95.6% vs. 63.8%, 48.9% vs. 23.4% and 26.7% vs. 14.9%, respectively. There were statistical differences in the immunohistochemistry of AFP, HER2, VEGF, GPC3, SALL4, P53 and Ki67 between the two groups ( χ2=67.758, P<0.001; χ2=4.004, P=0.044; χ2=19.299, P<0.001; χ2=5.232, P=0.022; χ2=6.359, P=0.012; χ2=6.224, P=0.013; χ2=5.232, P=0.022). The more co-positive expressions of AFP, GPC3, VEGF and SALL4, the more likely they were to affect pTNM stage, vascular invasion and liver metastasis ( χ2=5.328, P=0.021; P=0.013; χ2=5.887, P=0.015; χ2=3.923, P=0.048). Univariate and multivariate survival analysis of serum AFP positive gastric cancer showed:AFP, GPC3, VEGF and SALL4 were risk factors for AFP positive gastric cancer ( HR=3.700, P=0.036; HR=4.237, P=0.003; HR=3.916, P=0.004; HR=3.412, P=0.001). Conclusions:Serum AFP positive gastric cancer is a rare and highly invasive special type of gastric cancer. AFP, GPC3, VEGF and SALL4 are overexpressed in serum AFP positive gastric cancer, which is correlated with tumor stage, vascular invasion and liver metastasis. The final diagnosis of serum AFP positive gastric cancer still needs immunohistochemical examination. Preoperative serum AFP level is an important basis for AFP positive gastric cancer screening and AFP immunohistochemical examination.

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal

Objective:To compare the effectiveness, safety and postoperative recurrence of percutaneous nephrolithotomy (PCNL) with Holmium laser for upper urinary calculi in Uyghur and Han pediatric patients.Methods:The data of 123 Uyghur and 71 Han pediatric patients with upper urinary calculi admitted to First People's Hospital of Kashgar, Xinjiang and Beijing Friendship Hospital, Capital Medical University respectively, from August 2018 to August 2023, were retrospectively reviewed. The gender [males 73 (59.3%) vs.46 (64.8%) ], laterality (single/bilateral: 94/29 vs. 59/12), hydronephrosis [115 (93.5%) vs. 63 (88.7%)] and anatomical abnormalities [2(1.6%) vs. 5(7.0%)] of Uyghur and Han children were not statistically significant ( P>0.05). Uyghur children were older than Han children [5 (3, 7) vs. 3 (2, 6) years old], with a higher proportion of emaciated children [27 (21.9%) vs. 6 (8.5%) cases], a larger maximum stone diameter [(2.30±0.78) vs. (1.96±1.50) cm] and a lower proportion of multiple stones [46 (37.4%) vs. 52 (73.2%) cases] (all P<0.05). All the patients were treated with Holmium laser PCNL. The channels of the procedures in this study include F12-18 small channels and visual puncture channels. The operation datas, stone-free rate (SFR), complication rate (CR) and stone recurrence rate of the two groups were compared. Meanwhile, multiple logistic regression analysis was used to explore the factors influencing these indicators. Results:The operation time for Uyghur children was significantly longer than that of Han children [75.0 (58.0, 93.0) vs. 30.0 (20.0, 48.8) min]. Additionally, a greater proportion of Uyghur children underwent PCNL with F12-18 small channels than Han children [119 (96.7%) vs. 49(69.0%) cases]. The SFR [89.4%(110/123)vs.88.7%(63/71)], and postoperative CR [31.7%(39/123)vs. 26.8%(19/71)] in Uyghur and Han patients were not significantly different (all P>0.05). The recurrence rate in Uyghur children was higher than that observed in Han children [28.1%(25/89) vs. 15.6%(10/64), P=0.033]. The multivariate logistic regression analysis results indicated that the maximum stone diameter was an independent risk factor for SFR in both groups ( OR=0.401, 95% CI 0.191-0.842, P=0.016). Similarly, maximum stone diameter ( OR=1.896, 95% CI 1.088-3.304, P=0.024) and multiple stones ( OR=3.225, 95% CI 1.409-7.384, P=0.024) were identified as independent risk factors for CR. Ethnicity was not independent risk factor for SFR( OR=0.679, 95% CI 0.215-2.140), CR( OR=1.047, 95% CI 0.495-2.215) and stone recurrence rate( OR=0.820, 95% CI 0.285-2.356, all P>0.05). Conclusions:In comparison to Han pediatric patients during the same period, Holmium laser PCNL had similar SFR and CR for treating Uyghur children with upper urinary calculi, who were older, more emaciated and had larger average stone diameters. The higher postoperative recurrence rate of Uyghur children is likely to be associated with higher stone burden. The multivariate logistic regression analysis results showed that ethnicity was not an influential factor in SFR, complication rates, and stone recurrence rates. The findings need to be further validated in larger prospective cohort studies.

OBJECTIVE: To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies. METHODS: 10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13. RESULTS: The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly. CONCLUSION The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.
Pregnancy ; Female ; Humans ; Trisomy/genetics* ; Retrospective Studies ; Prenatal Diagnosis/methods* ; Down Syndrome/genetics* ; Aneuploidy ; Chromosome Aberrations ; Trisomy 18 Syndrome/genetics* ; Sex Chromosome Aberrations ; Fetus

Radical pelvic surgery is a surgical method mainly used to treat tumors in the pelvic cavity, and erectile dysfunction (ED) is a common sexual dysfunction after surgery. The incidence of ED after radical pelvic surgery is not uniformly understood due to differences in surgical approaches and methods of investigation. The main causes of postoperative ED include intraoperative neurovascular injury, psychosomatic factors and preoperative patient characteristics, with intraoperative injury to the neurovascular bundle being the most common. Studies have shown that the occurrence of postoperative ED can be prevented by active intervention, but still lack of effective treatment measures. This article reviews and summarizes the clinical epidemiological features and research progress in recent years on ED after radical pelvic surgery, and discusses specific measures for the prevention and treatment of postoperative ED.