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.

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 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.

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

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CX_AE, CX_AL, CX_PA and CX_PHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CX_AE, CX_AL and CX_PHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CX_AE and CX_PHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CX_PHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CX_PHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CX_PHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

Objective:To observe any effect of virtual reality (VR) training on the cognitive functioning and functional fitness of nursing home residents with subjective cognitive decline (SCD).Methods:Fifty-six of such residents were randomly divided into an observation group and a control group, each of 28. Both groups received health education and routine care, but the observation group was additionally provided with 45 minutes of VR training three times a week for 6 months. The training included Baduanjin, magic, flying bird, supermarket shopping, gravity ball and gym episodes. Both groups′ cognition was evaluated using the subjective cognitive decline questionnaire (SCD-Q), the Montreal cognitive assessment (MoCA), the Rivermead Behavioural Memory Test (second edition) (RBMT-Ⅱ), a digit symbol substitution test (DSST), an animal fluency test (AFT) and trail-making test A-B (TMT A-B). Functional fitness was quantified using the 8-foot up-and-go test (8UGT), a 30-second arm curl test (30sACT), a 30-second chair stand test (30sCST), a back scratching test (BST), the sit-and-reach test (CSRT) and a 2-minute step test (2MST) before and after the 6-month intervention.Results:After the intervention, the average SCD-Q, MoCA, RBMT-Ⅱ, DSST, TMT-A, and TMT-B scores of the observation group were significantly better than before the intervention, and significantly better than the control group′s averages. And except for the back scratching their functional results were also significantly better, on average, than those of the control group.Conclusions:VR training can effectively improve the cognition and functional fitness of nur-sing home residents with SCD. Such training is worthy of promotion and wider application in nursing homes.

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.

Objective:To analyze the detection rate and related factors of depressive and anxious symptoms comorbidity in 2021 and 2022.Methods:Based on the results of the Seventh National Population Census in 2021,the residents of 32 provinces,municipalities,and autonomous regions were sampled by gender and age.The gender and age of the samples were in line with the characteristics of China's population.A face-to-face interview survey was conducted in community residents in each province in 2021(n=11 005)and 2022(n=30 421)with the Gen-eralized Anxiety Questionnaire-7 and Patient Health Questionnaire-9.Results:The detection rates of depressive and anxious symptoms comorbidity were 10.67％in 2021 and 11.72％in 2022.The prevalence of depressive and anxi-ety comorbidity were higher in male,younger(age≤17 years),divorced,lower BMI(BMI＜18.5 kg/m2),higher education(graduate),students,and residents with chronic medical history(Ps＜0.001).In 2022,32.06％of people with depressive symptoms had anxious symptoms and 47.62％of people with anxious symptoms had depressive symptoms.Conclusion:In 2021 and 2022,the detection rates of depressive and anxious symptoms comorbidity were both about 10％,and half of patients with anxious symptoms were accompanied by depressive symptoms,So atten-tion should be paid to the comorbidity of depression and anxiety symptoms.

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.