Objective: To investigate the effect of integrin α5 on the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) in periodontal ligament fibroblasts (PDLFs) within an inflammatory microenvironment. Methods: This study was approved by the Ethics Committee of Laboratory animals. After rat PDLFs were treated with LPS (0.5, 5, and 50 µg/mL) for 24 h, the primary medium was discarded and replaced with serum-free culture medium. After 24 h, the supernatant was collected and mixed with DMEM medium containing 10% exosome-free serum at a volume ratio of 1:1 to obtain conditioned medium (CM). The groups were labeled as the 0.5-CM, 5-CM, and 50-CM groups. In addition, PDLFs cultured in DMEM medium containing 10% exosome-free serum were considered the 0-CM group. PDLFs were cultured with the above CM. In the inhibitor group, PDLFs were cultured in 0-CM containing different concentrations of integrin α5 inhibitor ATN-161 (0, 0.025, 0.25, 2.5, 25, and 250 μg/mL). The effect of CM and integrin α5 inhibitor ATN-161 on cell viability was assessed using the CCK-8 assay. According to the CCK-8 results, in further inhibitor intervention experiments, PDLFs were cultured in 0-CM, 5-CM (without/with 25 μg/mL ATN-161), and 0-CM containing 25 μg/mL ATN-161, which were labeled as the 0-CM, 5-CM, ATN-161+5-CM, and ATN-161 groups, respectively. The expression changes of integrin α5 and NLRP3 were detected using Western blot and qRT-PCR techniques. For in vivo experiments, 24 rats were randomly divided into four groups (n=6). The control group contained healthy rats that received no treatment. The rats in the other three groups were injected with 40 µL of 0-CM containing 25 μg/mL ATN-161 or 5-CM (without or with 25 μg/mL ATN-161) on the palatal side of the left maxillary first molar every three days; these groups were classified as the ATN-161, 5-CM, and ATN-161+5-CM groups, respectively. On the 30th day, the left maxillary tissue of rats was used for Micro-CT, HE staining, and immunohistochemical detection. Results : The CCK-8 assay showed that CM, 25 μg/mL ATN-161, and ATN-161 concentrations below 25 μg/mL had no significant effect on cell viability at 12 h and 24 h (P > 0.05). 50-CM and 25 μg/mL ATN-161 significantly inhibited cell viability at 48 h (P < 0.05). For in vitro experiments, compared to the 0-CM group, both the protein and mRNA levels of integrin α5 and NLRP3 were significantly increased in rat PDLFs in the 5-CM group (P < 0.05). Intervention with 25 μg/mL ATN-161 significantly attenuated the enhancement of 5-CM on the expression of integrin α5 and NLRP3 (P < 0.05). For in vivo experiments, compared to the control group, alveolar bone resorption and periodontal inflammatory cell infiltration were significantly increased in the 5-CM and ATN-161+5-CM groups, and the expression of integrin α5 and NLRP3 was significantly increased (P < 0.01). However, compared to the 5-CM group, the ATN-161+5-CM group had less alveolar bone resorption and fewer periodontal inflammatory cells. Further, the expression of integrin α5 and NLRP3 was significantly reduced (P < 0.01). Conclusion In vitro and in vivo experiments showed that integrin α5 mediated NLRP3 expression in PDLFs under an inflammatory microenvironment. ATN-161 inhibited the expression of integrin α5, thus significantly downregulating the expression of NLRP3, which plays a role in inhibiting inflammation.

Aim To explore the mechanism of modified Wuzi Yanzong pill to reduce testicular toxicity of Tripterygium wilfordii by means of network pharmacolo-gy.Methods The effective chemical composition and target of modified Wuzi Yanzong Pill to reduce testicu-lar toxicity of Tripterygium wilfordii were analyzed by using multiple databases to understand the mechanism of action.Results The first five compounds of modi-fied Wuzi Yanzong pill are quercetin,sucrose,kaempferol,galactose and ellagic acid,respectively.The first five targets were TP53,SRC,EP300,MAPK3,STAT3;KEGG pathway enrichment analysis mainly concentrated in cancer pathway,lipid and atherosclero-sis,hepatitis B,apoptosis,diabetes complications AGE-RAGE signaling pathway,PI3K-Akt signaling pathway and other signaling pathways.Conclusions The ac-tive components of modified Wuzi Yanzong pill can re-duce the testicular toxicity of Tripterygium wilfordii mainly by interfering with TP53,SRC,EP300,MAPK3,STAT3 and other targets,regulating apoptosis,PI3K-Akt signaling pathway,diabetes complications AGE-RAGE signaling pathway,lipid metabolism and other pathways.

AIM To analyze the metabolites of nobiletin in rats in vivo based on characteristic ions.METHODS Ten rats were assigned into administration group and control group,and given intragastric administration of the 0.5％CMC-Na suspension of nobiletin(250 mg/kg)and 0.5％CMC-Na solution,respectively,after which plasma,urine and feces were collected,solid phase extraction method was adopted in pretreatment,UHPLC-HRMS analysis was performed.The candidate metabolites were systematically described according to diagnostic product ions,chromatographic retention time,accurate molecular weight and neutral loss fragments,after which accurate metabolites were obtained in the established metabolite data set with-CH3(m/z 15)characteristic ions as a baits.RESULTS A total of 64 metabolites were identified,whose main metabolic pathways were glucuronidation,sulfation,hydrogenation and their compound reactions.CONCLUSION This experiment elucidates the metabolites of nobiletin in rats in vivo,which provides a new reference for its further development.

AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P＜0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P＜0.05,P＜0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P＜0.05,P＜0.01);decreased protein expressions of FoxO1 and Murf1(P＜0.05,P＜0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P＜0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.

Objective:To investigate the clinical characteristics of cases with different congenital pulmonary airway malformations (CPAM) volume ratios (CVR) and the effect of maternal glucocorticoid treatment during pregnancy on CPAM.Methods:A retrospective study was conducted on 56 singleton pregnant women with fetal CPAM diagnosed prenatally in the Department of Obstetrics and Gynecology at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, from September 2020 to May 2023. Among these, three cases received maternal glucocorticoid treatment during pregnancy and clinical conditions were reported in detail. Statistical analyses were performed using independent sample t-tests, non-parametric tests, Chi-square tests, or Fisher's exact test. Results:(1) General information: The average age of the 56 pregnant women with CPAM fetuses was (32.0±0.7) years. All fetuses had unilateral lesions, with 25 cases (44.6%) on the left side. Types Ⅰ, Ⅱ, and Ⅲ CPAM accounted for 5.4% (3/56), 50.0% (28/56), and 44.6% (25/56), respectively. Fetal hydrops occurred in two cases, and the maximum CVR during the fetal period for the other 54 non-hydropic fetuses was 0.79±0.66. (2) The CVR threshold for the risk of fetal hydrops was set as the mean maximum CVR of non-hydropic CPAM fetuses plus 2 standard deviations (0.79+2×0.66=2.1). The subjects were divided into two groups based on the maximum CVR during the fetal period: CVR≤2.0 group ( n=50) and CVR>2.0 group ( n=6). Comparison between the CVR>2.0 group and CVR≤2.0 group: The CVR>2.0 group had significantly higher rates of fetal hydrops [2/6 vs. 0.0% (0/50), Fisher's exact test], mediastinal shift [5/6 vs. 32.0% (16/50), χ 2=4.03], polyhydramnios [6/6 vs. 4.0% (2/50), Fisher's exact test], and postnatal surgery [4/5 vs. 22.2% (10/45), continuity correction χ 2=4.86] (all P<0.05). None of the fetuses with CVR≤2.0 had hydrops or received intrauterine intervention. The overall live birth rate was 89.3% (50/56). (3) Maternal glucocorticoid treatment during pregnancy: three of six fetuses with CVR>2.0 were treated with maternal glucocorticoid during pregnancy, and all were delivered alive at term after the intervention with resolution of edema and/or reduction in mass size. Two of them were treated with postnatal thoracoscopic surgery and were followed up to 5 and 14 months of age, respectively, with no abnormalities in feeding and development; the other was not treated surgically until 3 months of age, with no respiratory-related symptoms and no abnormalities in feeding and development. Conclusions:Prenatal ultrasound indicating CVR>2.0 is associated with increased rates of fetal hydrops, mediastinal shift, and polyhydramnios. Maternal glucocorticoid treatment during pregnancy may lead to favorable pregnancy outcomes for these CPAM fetuses.

Objective:To investigate the feasibility of predicting the risk of spontaneous preterm birth in singleton pregnancy women with low risk of preterm birth by transabdominal-transvaginal ultrasound cervical length sequential screening in the second trimester.Methods:This prospective longitudinal cohort study included singleton pregnant women at 11-13 +6 gestational weeks who were admitted to Nanjing Drum Tower Hospital from January 2023 to September 2023. Transabdominal and transvaginal cervical lengths were measured during the mid-trimester fetal ultrasound scan at 18-24 weeks, and pregnancy outcomes were obtained after delivery. A short cervix was defined as a transvaginal cervical length of ≤25 mm, and the outcomes were defined as spontaneous preterm birth occurs between 20 and 36 +6 weeks and extremely preterm birth before 32 weeks. The area under the receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of predicting spontaneous preterm birth by transabdominal and transvaginal cervix length, as well as the effectiveness of predicting short cervix by transabdominal cervical length. The relationship between transabdominal and transvaginal cervical length was evaluated using a scatter plot. Results:A total of 562 cases were included in this study, comprising 33 cases of spontaneous preterm birth (7 cases occurring before 32 weeks) and 529 cases of term birth. (1) Compared to the term birth group, transabdominal cervical length (median: 37.6 vs 33.2 mm; Z=-3.838, P<0.001) and transvaginal cervical length (median: 34.0 vs 29.9 mm, Z=-3.030, P=0.002) in the spontaneous preterm birth group were significantly shorter. (2) The areas under the ROC curve for predicting spontaneous preterm birth by transabdominal and transvaginal cervical length were 0.699 (95% CI: 0.588-0.809) and 0.657 (95% CI: 0.540-0.774), respectively. The sensitivity, specificity and positive predictive value of transvaginal cervical length Conclusions:In singleton pregnancy women with low risk of preterm birth, transabdominal-transvaginal cervical length sequential screening can reduce unnecessary transvaginal ultrasounds by approximately 41% without missing the diagnosis of pregnant women with a short cervix. This method also enhances the effectiveness of transvaginal cervical length to spontaneous preterm birth.

Objective To study the effects of scutellarin on endometrial carcinoma Ishikawa cells,and analyze the correlation between the effects and phosphatidyl inositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway.Methods Ishikawa cells were divided into blank group and experimental-L,-M,-H groups,each group was treated with complete medium containing 0,5,10 and 20 μmol·L-1 scutellarin,respectively.Cell viability,clonal formation ability,metastatic ability,invasion,apoptosis and protein expression were detected by cell counting kit-8(CCK-8),plate cloning,scratch,Transwell,flow cytometry and Western blot assay,respectively.Results The cell viability of blank group and experimental-L,-M,-H groups at 48 h were(100.00±0.00)％,(78.51±7.54)％,(52.93±4.91)％and(41.62±5.33)％;the clone formation rate were(100.00±0.00)％,(56.59±6.34)％,(35.23±4.62)％and(10.66±1.91)％;the scratch healing rate were(53.70±6.19)％,(40.59±4.75)％,(34.25±4.40)％and(15.78±2.14)％;the number of invasive cells were 189.70±14.06,106.82±12.67,84.37±8.13 and 53.74±6.78;the relative expression levels of matrixmetallo proteinase-2 were 0.96±0.10,0.73±0.06,0.68±0.08 and 0.42±0.05;tissue inhibitor of MMP-1(TIMP-1)were 0.35±0.04,0.51±0.05,0.74±0.08 and 1.20±0.14;the apoptosis rates were(4.21±0.53)％,(15.83±2.42)％,(22.72±3.85)％and(34.41±4.67)％;the relative expression levels of B cell lymphoma-2(Bcl-2)were 1.38±0.15,0.90±0.10,0.56±0.06 and 0.24±0.03;Bcl-2 associated X protein(Bax)were 0.31±0.02,0.44±0.04,0.93±0.11 and 1.26±0.14;the relative expression levels of PI3Kp85 were 0.67±0.05,0.42±0.04,0.36±0.02 and 0.28±0.03;phosphorylated Akt(p-Akt)were 0.78±0.06,0.53±0.04,0.46±0.05 and 0.42±0.03.Compared with the blank group,the above indexes in the experimental-L,-M,-H groups were statistically significant(P＜0.05 or P＜0.01).Conclusion Scutellarin can inhibit the proliferation,metastatic ability and invasion of endometrial carcinoma Ishikawa cells and promote apoptosis by regulating PI3K/Akt signaling pathway.

Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.

Allergic diseases affect about 40% of the world's population. Environmental factors are important in the occurrence and development of allergic diseases. Dust mites are one of the most important allergens in the indoor environment. The World Health Organization proposes the "four-in-one, combination of prevention and treatment" treatment principle for allergic diseases, in which environmental control to avoid or reduce allergens is the first choice for treatment. Modern people spend much more time at home (including sleeping) than outdoors, and the control of the home environment is particularly critical. This practice introduces the hypoallergenic home visit program, which including home environment assessment, environmental and behavioral intervention guidance, and common household hypoallergenic supplies and service guidance for the patient's home environment. The real-time semi-quantitative testing of dust mite allergens, qualitative assessments of other indoor allergens, record of patients' household items and lifestyle, and precise, individualized patient prevention and control education will be conducted. The hypoallergenic home visit program improves the doctors' diagnosis and treatment data dimension, and becomes a patient management tool for doctors outside the hospital. It also helps patients continue to scientifically avoid allergens and irritants in the environment, effectively build a hypoallergenic home environment, reduce exposure to allergens in the home environment, and achieve the goal of combining the prevention and treatment of allergic diseases.
Humans ; Hospitals ; Life Style ; Sleep

Objective: To establish neonatal birthweight percentile curves based on single-center cohort database using different methods, compare them with the current national birthweight curves and discuss the appropriateness and significance of single-center birthweight standard. Methods: Based on a prospective first-trimester screening cohort at Nanjing Drum Tower Hospital from January 2017 to February 2022, the generalized additive models for location, scale and shape (GAMLSS) and semi-customized method were applied to generate local birthweight percentile curves (hereinafter referred to as the local GAMLSS curves, semi-customized curves) for 3 894 cases who were at low risk of small for gestation age (SGA) and large for gestation age (LGA). Infants were categorized as SGA (birth weight<10th centile) by both semi-customized and local GAMLSS curves, semi-customized curves only, or not SGA (met neither criteria). The incidence of adverse perinatal outcome between different groups was compared. The same method was used to compare the semi-customized curves with the Chinese national birthweight curves (established by GAMLSS method as well, hereinafter referred to as the national GAMLSS curves). Results: (1) Among the 7 044 live births, 404 (5.74%, 404/7 044), 774 (10.99%, 774/7 044) and 868 (12.32%, 868/7 044) cases were diagnosed as SGA according to the national GAMLSS curves, the local GAMLSS curves and the semi-customized curves respectively. The birth weight of the 10th percentile of the semi-customized curves was higher than that of the local GAMLSS curves and the national GAMLSS curves at all gestational age. (2) When comparing semi-customized curves and the local GAMLSS curves, the incidence of admission to neonatal intensive care unit (NICU) for more than 24 hours of infants identified as SGA by semi-customized curves only (94 cases) and both semi-customized and local GAMLSS curves (774 cases) was 10.64% (10/94) and 5.68% (44/774) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks of infants identified as SGA by the semi-customized curves only and both semi-customized and local GAMLSS curves was 12.77% (12/94) and 9.43% (73/774), 9.57% (9/94) and 2.71% (21/774), 24.47% (23/94) and 7.24% (56/774) respectively, which were significantly higher than those of the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. (3) When comparing semi-customized curves and the national GAMLSS curves, the incidence of admission to NICU for more than 24 hours of infants identified as SGA by semi-customized curves only (464 cases) and both semi-customized and national GAMLSS curves (404 cases) was 5.60% (26/464) and 6.93% (28/404) respectively, both significantly higher than that in non SGA group [6 176 cases, 1.34% (83/6 176); all P<0.001]. The incidence of emergency cesarean section or forceps delivery for non-reassuring fetal status (NRFS) in infants identified as SGA by semi-customized curves only and both semi-customized and national GAMLSS curves was 4.96% (23/464) and 12.38% (50/404), both significantly higher than that in the non SGA group [2.57% (159/6 176); all P<0.001]. The incidence of preeclampsia, pregnancy<34 weeks, and pregnancy<37 weeks in the semi-customized curves only group and both semi-customized and national GAMLSS curves group was 8.84% (41/464) and 10.89% (44/404), 4.31% (20/464) and 2.48% (10/404), 10.56% (49/464) and 7.43% (30/404) respectively, all significantly higher than those in the non SGA group [4.37% (270/6 176), 0.83% (51/6 176), 4.23% (261/6 176); all P<0.001]. Conclusion: Compared with the national GAMLSS birthweight curves and the local GAMLSS curves, the birth weight curves established by semi-customized method based on our single center database is in line with our center' SGA screening, which is helpful to identify and strengthen the management of high-risk infants.
Female ; Humans ; Infant, Newborn ; Pregnancy ; Birth Weight ; Cesarean Section ; Gestational Age ; Infant, Small for Gestational Age ; Pre-Eclampsia/epidemiology* ; Prospective Studies