Objective: To analyze the differences in bile acid profiles during different pregnancy durations of patients with intrahepatic cholestasis of pregnancy (ICP), so as to provide a reference for early prevention and treatment of ICP and optimization of maternal-infant health outcomes. Methods: Pregnant women who underwent routine prenatal examinations and delivered at Hangzhou Obstetrics and Gynecology Hospital from 2021 to 2023 were selected as study subjects. According to the ICP guidelines (2020), pregnant women were categorized into normal group, mild ICP group, and moderate/severe ICP group. Age, parity, and gravidity were collected through the obstetric electronic medical record system, liver function indicators and seven bile acid levels were collected through the hospital's laboratory information system. Differences in bile acid profiles across pregnancy durations among the three groups were compared. Results: A total of 238 pregnant women were enrolled, including 57 cases (23.95%) in the normal group, 136 cases (57.14%) in the mild ICP group, and 45 cases (18.91%) in the moderate/severe ICP group. There were statistically significant differences between the three groups in total bile acid (TBA), cholic acid (CA), chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), glycocholic acid (GCA), taurocholic acid (TCA) levels (all P<0.05). Compared with the normal group, CA, GCDCA and GCA, and TCA were higher in the mild and moderate/severe ICP groups; compared with the mild ICP group, GCA was higher in the moderate/severe ICP group (all P<0.05). Significant differences were observed in the levels of GCDCA, GCA, and TCA among three groups pregnant women in the early, mid, and late pregnancy (all P<0.05). Compared with the normal group, mild ICP group had higher GCDCA and GCA in the early and mid pregnancy; moderate/severe ICP group had higher TCA in the early pregnancy and higher GCDCA and GCA in the late pregnancy. Compared with the mild ICP group, mild ICP group had higher TCA in the early pregnancy and the moderate/severe ICP group had higher GCA in the late pregnancy. Conclusions GCDCA, GCA, and TCA levels remain higher in ICP patients than in normal pregnant women across all pregnancy durations. Personalized perinatal management plans can be developed based on bile acid profile dynamics to optimize maternal-fetal outcomes.

OBJECTIVE: To observe the regulatory effects of moxibustion at "Guanyuan" (CV4) on the synthesis of extragonadal estradiol (E₂) and the expression of estrogen receptor (ER) in ovariectomized rats, aiming to explore the mechanism of moxibustion treatment for perimenopausal syndrome. METHODS: Forty-eight SD female rats of SPF grade were randomly divided into a sham-operation group, a model group and a moxibustion group, with 16 rats in each group. The model group and the moxibustion group underwent bilateral ovariectomy by the back incision method. Ten days after surgery, moxibustion was applied at "Guanyuan" (CV4) in the moxibustion group, 30 min each time, once a day for 10 days. After intervention, in the 3 groups, the body mass and uterus weight were measured; the serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and E₂, as well as the skin and hypothalamus levels of E₂ were detected by ELISA; the mRNA expression of aromatase (P450arom) in the skin and hypothalamus was detected by real-time PCR; the expression of ERα and ERβ in the hypothalamus, skin, and uterus was observed by immunofluorescence staining, and the density of positive cells was calculated using the Aipathwell digital pathology image analysis software. RESULTS: Compared with the sham-operation group, the body mass was increased (P<0.01) and the uterus weight was decreased (P<0.001) in the model group. Compared with the model group, the body mass was decreased in the moxibustion group (P<0.01). Compared with the sham-operation group, in the model group, the serum, hypothalamus and skin levels of E₂ were decreased (P<0.01, P<0.05), while the serum levels of FSH and LH were increased (P<0.01); the expression of ERα and ERβ in the skin, hypothalamus and uterus was decreased (P<0.05, P<0.001). Compared with the model group, in the moxibustion group, the serum levels of E₂ and LH, as well as the hypothalamus and skin levels of E₂ were increased (P<0.05, P<0.01); the mRNA expression of P450arom, as well as the expression of ERα and ERβ in the skin and hypothalamus were increased (P<0.05). CONCLUSION Moxibustion at "Guanyuan" (CV4) reduces the body mass of ovariectomized rats by enhancing the synthesis of extragonadal E₂ and increasing the expression of ER in the skin and hypothalamus, yet it does not alleviate uterine atrophy.
Animals ; Female ; Moxibustion ; Rats ; Ovariectomy ; Acupuncture Points ; Rats, Sprague-Dawley ; Humans ; Receptors, Estrogen/genetics* ; Estrogens/metabolism* ; Estradiol/metabolism* ; Hypothalamus/metabolism* ; Follicle Stimulating Hormone/blood* ; Aromatase/genetics* ; Luteinizing Hormone/blood* ; Skin/metabolism*

OBJECTIVES: To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). METHODS: This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. RESULTS: The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). CONCLUSIONS GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve.
Adult ; Female ; Humans ; Genotype ; Ovarian Follicle/cytology* ; Ovarian Reserve/genetics* ; Ovulation Induction/methods* ; Polymorphism, Genetic ; Receptors, Androgen/genetics* ; East Asian People/genetics*

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Humans ; Oral Submucous Fibrosis/immunology* ; Extracellular Matrix/metabolism* ; Myofibroblasts

Objective:To explore the optimum opportunity for lumbodorsal muscles exercises of patients undergoing posterior lumbar decompression and instrumentation, and investigate its effect on the rehabilitation outcomes and kinesiophobia.Methods:A randomized controlled trial was used. By convenient sampling method, a total of 120 lumbar disc herniation patients were prospectively selected from Affiliated Nantong Hospital of Shanghai(Nantong Sixth People′s Hospital) from February 2020 to December 2021. The paitients were assigned to early group, middle group and late group, with 40 cases in each group. All patients were given routine postoperative care and lumbodorsal muscles exercises. The early group started to exercise 10th day after operation, the middle group started to exercise 3 weeks after operation, and the late group started to exercise 6 weeks after operation. The intervention effect was respectively evaluated by Japanese Orthopaedics Association (JOA) and Tampa Scale for Kinesiophobia (TSK).Results:There were 3, 1 and 1 missing cases in the early, middle and late group respectively, the age in the 3 groups were (56.05 ± 11.77), (57.33 ± 14.64) and (54.23 ± 15.73) years old in turn. Three months after exercising, the total score of JOA in the early, middle and late group were (25.32 ± 2.45), (24.44 ± 2.19) and (22.13 ± 1.58) in turn, the difference was significant ( F=23.64, P<0.05); the score of TSK in the early, middle and late group were (37.95 ± 6.81), (34.18 ± 6.39) and (33.33 ± 7.36) in turn, the difference was significant ( F=4.82, P<0.05). Conclusions:Lumbodorsal muscles exercises start at 3 weeks after operation can significantly improve the rehabilitation outcome of lumbar disc herniation patients undergoing posterior lumbar decompression and instrumentation, and will not increase the level of kinesiophobia, its can be consider as optimum opportunity for lumbodorsal muscles exercises.

Objective To investigate the value of 4D-CTA combined with SDF-1a/CXCR4 signaling pathway in evaluating the risk of intracranial aneurysm rupture.Methods Fifty patients with unruptured intracranial posterior communicating aneurysms and 50 patients with ruptured intracranial posterior communicating aneurysms were divided into unruptured group 1 and ruptured group 1.All patients underwent 4D-CTA examination and serumSDF-1alevel was detected.Non-ruptured group 1 was followed up for 12 months(After conservative treatment),on this basis,patients with ruptured posterior communicating aneurysms were included in ruptured group 2,and patients with unruptured posterior communicating aneurysms were included in non-ruptured group 2.Results The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in diagnosing ruptured intracranial posterior communicating aneurysms were all greater than 0.70.The AUC values of Wn,AR,L,SR,SDF-1a and their combinations in predicting ruptured intracranial posterior communicating aneurysms in ruptured group 2 were all greater than 0.70.Conclusion 4D-CTA combined with SDF-1acan effectively distinguish ruptured intracranial posterior communicating aneurysms and predict the risk of rupture.

Objective To measure vaginal wall parameters including vaginal wall thickness,length and number of rugae in normal childbearing period women using transrectal biplane high-frequency ultrasonography,and to establish normal reference ranges of the above indexes.Methods Totally 245 normal childbearing period female volunteers were prospectively recruited.The thickness and length of vaginal wall were measured,and number of rugae were counted with transrectal biplane high-frequency ultrasound,and the normal reference ranges were established.The correlations of the above indexes with age,height,body mass and body mass index(BMI)were explored.Results The thickness and length of vaginal wall was(7.50-16.20)mm(95％CI[11.43,11.92]mm)and(3.30-7.61)cm(95％CI[5.35,5.74]cm),respectively,and number of rugae was 5.00±15.00(95％CI[8.42,9.13]).Both the length of vaginal wall and the number of rugae were negatively correlated with age(r=-0.145,-0.178;P=0.024,0.005),while the thickness of vaginal wall was not obviously correlated with age,height,body mass and BMI of normal childbearing period women(all P＞0.05).Conclusion The normal reference ranges of the thickness and length of vaginal wall,as well as the number of rugae in normal childbearing period established women obtained with transrectal biplane high-frequency ultrasonography could provide references for clinical assessment of vaginal condition.

Objective To observe the value of ultrasonic parameters for predicting whether patients with cesarean scar pregnancy(CSP)would benefit from ultrasound-guided suction curettage alone.Methods Totally 140 CSP patients diagnosed by transvaginal ultrasound and initially treated with ultrasound-guided suction curettage alone were prospectively recruited and categorized into benefited group(n=103)and non-benefited group(n=37)according to bleeding during suction curettage and prognoses.The ultrasonic manifestations of CSP were observed,and the thickness of chorionic villi at the scar,as well as of residual myometrium of the anterior wall in the lower segment of the uterus,also the maximum diameter of the gestational sac were measured and compared between groups,and the parameters with quantitative data being statistically different between groups were converted into categorical predictor through analyzing of the receiver operating characteristic(ROC)curves and the optimal cut-off values.The independent predictors were selected among ultrasonic features and categorical predictor variables being statistically different between groups using multivariate logistic regression,and a combined predicting model was then constructed,and the predicting efficacy of the combined model and each categorical predictor alone was assessed according to the area under curve(AUC)and then were compared.Results Compared with non-benefited group,the gestational weeks in benefited group were smaller(P＜0.05),and the percentages of rich blood supply and the presence of embryos and fetal heartbeats were lower,with thinner chorionic villi at the scar,thicker residual myometrium and smaller maximal diameter of the gestational sac in benefited group(all P＜0.05).ROC curves analyses yielded the best cut-off value for dichotomy of chorionic villi thickness at the scar was 4.7 mm,of residual myometrium thickness was 1.8 mm and of the maximum diameter of the gestational sac was 29 mm,respectively,and then categorical predictor variable were obtained.Multivariate logistic regression showed that the transformed categorical predictors,i.e.the thickness degree of the chorionic villi at the scar,the thickness degree of the residual muscle layer and the size degree of the gestational sac,were all independent predictors of whether CSP patients would benefit from ultrasound-guided suction curettage alone(all P＜0.05).The AUC of the combined predicting model was 0.918,higher than that of each transformed categorical predictor alone(all P＜0.05).Conclusion The thickness of the chorionic villi at the scar ≤4.7 mm,the thickness of the residual muscle layer＞1.8 mm and the maximum diameter of the gestational sac≤29 mm were all independent predictors of CSP patients would benefit from ultrasound-guided suction curettage alone,and the predicting efficacy of the combined model was higher than that of each alone.

Objective To investigate the effects of esketamine on hypoxic-ischemic myocardial injury in neonatal rats based on glycogen synthase kinase-3β/NOD-like receptor thermal protein domain-containing protein 3 (GSK-3β/NLRP3) pathway. Methods Thirty neonatal rats were randomly divided into sham operation group, model group and esketamine group, with 10 rats in each group. The rats in the sham operation group underwent a median incision in the neck to expose the bilateral common carotid arteries; the rats in the model group and the esketamine group underwent ligation of the common carotid arteries combined with a hypoxic environment to establish a model ofischemia and hypoxia; the rats in the esketamine group were given esketamine intervention (50 mg/kg). Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β levels, myocardial injury, myocardial cell apoptosis and apoptosis protein caspase 1/3/9 levels, neutrophil infiltration in myocardial tissue, and changes in GSK-3β and NLRP3 protein levels in myocardial tissue were detected in each group. Results Compared with the sham operation group, the LVEF and LVFS were significantly decreased and the LVEDD and LVESD were significantly increased in the model group, while the LVEF and LVFS were significantly higher and the LVEDD and LVESD were significantly lower in the esketamine group than in the model group (P < 0.05). The serum levels of CK-MB, cTnI, LDH, TNF-α, IL-6, IL-1β, myocardial injury and apoptosis, caspase 1/3/9 protein levels in myocardial tissue sections, neutrophil counts, and GSK-3β and NLRP3 protein levels were significantly increased in the model group, and these indicators were significantly lower in the esketamine group than in the model group (P < 0.05). Conclusion Esketamine improves hypoxic-ischemic myocardial injury in neonatal rats by inhibiting inflammation, and its mechanism of action is related to the GSK-3β/NLRP3 pathway.

Chemotherapy is currently the main clinical treatment method for malignant tumors， and chemotherapy resistance is the main factor leading to chemotherapy failure and malignant tumor recurrence and metastasis. The cha-racteristics of malignant tumors formation were regarded as similar to the “Yin Fire” theory， manifested that deficiency of original qi as the foundation of malignant tumors， imbalance of original qi and yin fire as the internal cause of malignant tumor progression， and the internal environment of phlegm-blood stasis-toxicity-deficiency caused by yin fire promoted the formation of chemoresistance. In the treatment of chemoresistance of malignant tumors， traditional Chinese medicine should focus on treating disease before its onset by tonifying the spleen and strengthening the middle， nou-rishing the original qi， and reinforcing healthy qi and anti-cancer； during the treatment， the clinicians should regulate the qi and detoxify to clear yin fire， and improve the internal environment. Summarily， the strategies were adjusting the balance of internal environment of original qi and yin fire， and conducting a comprehensive treatment during the whole process， to provide new ideas for the treatment of chemoresistance of malignant tumors with traditional Chinese medicine.