Development and validation of machine-learning models of diet management for hyperphenylalaninemia: a multicenter retrospective study.

BACKGROUND: Assessing dietary phenylalanine (Phe) tolerance is crucial for managing hyperphenylalaninemia (HPA) in children. However, traditionally, adjusting the diet requires significant time from clinicians and parents. This study aims to investigate the development of a machine-learning model that predicts a range of dietary Phe intake tolerance for children with HPA over 10 years following diagnosis. METHODS: In this multicenter retrospective observational study, we collected the genotypes of phenylalanine hydroxylase (PAH), metabolic profiles at screening and diagnosis, and blood Phe concentrations corresponding to dietary Phe intake from over 10 years of follow-up data for 204 children with HPA. To incorporate genetic information, allelic phenotype value (APV) was input for 2965 missense variants in the PAH gene using a predicted APV (pAPV) model. This model was trained on known pheno-genotype relationships from the BioPKU database, utilizing 31 features. Subsequently, a multiclass classification model was constructed and trained on a dataset featuring metabolic data, genetic data, and follow-up data from 3177 events. The final model was fine-tuned using tenfold validation and validated against three independent datasets. RESULTS: The pAPV model achieved a good predictive performance with root mean squared error (RMSE) of 1.53 and 2.38 on the training and test datasets, respectively. The variants that cause amino acid changes in the region of 200-300 of PAH tend to exhibit lower pAPV. The final model achieved a sensitivity range of 0.77 to 0.91 and a specificity range of 0.8 to 1 across all validation datasets. Additional assessment metrics including positive predictive value (0.68-1), negative predictive values (0.8-0.98), F1 score (0.71-0.92), and balanced accuracy (0.8-0.92) demonstrated the robust performance of our model. CONCLUSIONS: Our model integrates metabolic and genetic information to accurately predict age-specific Phe tolerance, aiding in the precision management of patients with HPA. This study provides a potential framework that could be applied to other inborn errors of metabolism.

Optimal range of gestational weight gain for singleton pregnant women: a cohort study based on Chinese specific body mass index categories.

BACKGROUND: The purpose was to explore the optimal proportion of GWG in Chinese singleton pregnant women according to Chinese specific body mass index (BMI) categories. METHODS: A retrospective cohort study with 16,977 singleton pregnant women was conducted. Among the including subjects, 2/3 of which were randomly imported into the training set for calculating the optimal GWG ranges using the percentile method, the Odd Ratio (OR) method, and the combined risk curve method. And another third of the subjects were used to evaluate the GWG ranges obtained. The detection rate of adverse outcomes of pregnant women was used to evaluate the applicability of GWG obtained. The range corresponding to the lowest detection rate is the recommended GWG range in this study. RESULTS: According to the percentile method, the suitable GWG of pregnant women with underweight, normal weight, overweight or obesity before pregnancy were 12.0 ∼ 17.5 kg, 11.0 ∼ 17.0 kg, and 9.0 ∼ 15.5 kg, respectively. According to the OR method, the suitable GWG range were 11 ∼ 18 kg, 7 ∼ 11 kg, and 6 ∼ 8 kg, respectively. According to the combined risk curve method, the suitable GWG range were 11.2 ∼ 17.2 kg, 3.6 ∼ 11.5 kg, and - 5.2 ∼ 7.0 kg, respectively. When the GWG for different BMI categories were 11 ∼ 18 kg, 7 ∼ 11 kg, and 6 ∼ 8 kg, the pregnant women have the lowest detection rate of adverse maternal and infant outcomes. CONCLUSIONS: The recommended GWG based on this study for underweight, normal, overweight or obese pregnant women were 11 ∼ 18 kg, 7 ∼ 11 kg, and 6 ∼ 8 kg, respectively.

Intra-abdominal umbilical venous diameter and abdominal circumference discordance at 15-20 weeks' gestation: simple markers in transverse abdominal plane to predict adverse pregnancy outcomes in monochorionic diamniotic twins.

PURPOSE: This study aimed to investigate the association between simple markers in fetal abdominal plane, intra-abdominal umbilical venous diameter (DIUV) and abdominal circumference (AC) discordance at 15-20 weeks' gestation, and adverse pregnancy outcomes in monochorionic diamniotic (MCDA) twins. METHODS: We performed a retrospective analysis of MCDA twins with two live fetuses examined at 15-20 weeks from Jun 2020 to Dec 2021 at Beijing Obstetrics and Gynecology Hospital. Measurement of fetal AC and DIUV was performed according to standard protocols. Twin pregnancies with major fetal structural anomalies, chromosomal abnormalities, miscarriage, and twin reversed arterial perfusion sequence were excluded. DIUV and AC discordance in MCDA twins with an adverse pregnancy outcome was compared with a normal pregnancy outcome. Furthermore, the performance of DIUV and AC discordance in predicting adverse pregnancy outcomes in MCDA twins was assessed. RESULTS: A total of 105 women with MCDA twin pregnancies were enrolled, contributing 179 visits. Adverse pregnancy outcomes occurred in 33.3% (35/105) of cases in our study. The intra-observer and inter-observer intraclass correlation coefficient (ICC) of both AC and DIUV were very good or excellent. There was no statistical difference in AC and DIUV discordance (%) between 15-16, 17-18, and 19-20 weeks (χ2 = 3.928, P = 0.140; χ2 = 2.840, P = 0.242). Both AC and DIUV discordance were greater in twins with adverse pregnancy outcomes than that in twins with normal pregnancy outcome at each pregnancy periods. Both AC discordance (OR 1.2, 95% CI 1.1-1.3) and DIUV discordance (OR 1.2, 95% CI 1.1-1.2) were associated with adverse pregnancy outcomes. The AUC for predicting adverse pregnancy outcomes by AC discordance was 0.75 (95% CI 0.68-0.83), with a sensitivity of 58.7% (95% CI 51.9-64.5) and a specificity of 86.2% (95% CI 81.7-88.4). The AUC for predicting adverse pregnancy outcomes by DIUV was 0.78 (95% CI 0.70-0.86), with sensitivity and specificity of 65.1% (95% CI 58.1-70.3) and 86.2% (95% CI 81.7-88.4), respectively. CONCLUSIONS: The AC discordance and DIUV discordance could predict adverse pregnancy outcomes in MCDA twins. When these simple markers occurred, intensive surveillance was recommended.

Effect of Prenatal Omega-3 Polyunsaturated Fatty Acid Supplementation on Childhood Eczema: A Systematic Review and Meta-Analysis.

It is uncertain about the effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy on the incidence of eczema among children. The aim of this review was to test if there is an effect of ω-3 PUFA supplementation during pregnancy on the risk of eczema among children of different ages. Two authors independently carried out the selection of published works, data extraction, and evaluation of the likelihood of bias. The PubMed, Medline, the Cochrane Library, Web of Science, and Embase databases updated to the date of March 2021 have been researched thoroughly for literature review. Quality Assessment of studies was evaluated using the updated tool (Rob2) provided by the Cochrane collaboration group. Six unique randomized controlled trials from 7 studies including 1,646 mother-infant pairs were contained in this review. Pooled data showed no pronounced decline in the incidence of eczema (RR = 1.09, 95% CI = 0.82~1.46, p = 0.54) or IgE-associated eczema (RR = 0.67; 95% CI = 0.29~1.57; p = 0.34). However, the subgroup analyses on "IgE-associated eczema" showed a significant decrease among the "≤3-year-old children" (RR = 0.70; 95% CI = 0.50~0.96; p = 0.03) in the ω-3 PUFAs group compared with the placebo. Supplementing the maternal diet with ω-3 PUFAs during pregnancy cannot reduce the danger of eczema or IgE-associated eczema among all children; however, there may be a subgroup-specific effect on 3-year-old or even younger children in reducing the incidence of IgE-associated eczema.

Blue and red upconversion color tuning of Tm3+ via pulse excitation based on the thermal effect.

Color-tunable upconversion luminescence has wide prospects for anti-counterfeiting and disease diagnosis/treatment. To date, achieving high-quality tunable red and blue emissions using a single excitation wavelength remains a formidable challenge, due to the large energy difference between the red and blue photons. In this Letter, based on Tm3+ upconversion luminescence, blue dominant and red dominant emissions are generated upon 980-nm excitations using a short and long pulse, respectively. The corresponding color tuning mechanisms are investigated based on the spectral observations. The proposed color tuning strategy is particularly useful for in vivo applications as the red and blue lights play important roles in biological imaging and drug release, respectively.

A dose-response meta-analysis of the association between the maternal omega-3 long-chain polyunsaturated fatty acids supplement and risk of asthma/wheeze in offspring.

BACKGROUND: Prenatal exposure to omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in oily fish may prevent asthma or wheeze in childhood. OBJECTIVE: By limiting n-3 LC-PUFA capsules interventions commenced in pregnancy, this systematic review aimed to find more clear evidence on the relationship between the supplement with n-3 LC-PUFA during pregnancy and the risk of asthma/wheeze in offspring and to improve the life satisfaction of children with asthma. METHODS: The Cochrane library, Embase, Medline, Web of Science, and PubMed were searched from origin to March 2021 in the above-mentioned databases. Studies selection, data of characteristics extraction, and risk of bias assessment were conducted by two authors, independently. A total of 3037 mother-infant pairs from eight randomized controlled trials were ultimately analyzed. The primary outcome was the risk of "asthma and/or wheeze", and the secondary outcome was "Allergic asthma" in this dose-response meta-analysis. Sensitivity analysis and subgroup analysis were conducted. The robust-error meta-regression model was used for dose-response analysis. RESULTS: This meta-analysis showed that n-3 LC-PUFA during pregnancy did not obviously reduce the risk of asthma/wheeze (RR 0.93; 95% CI 0.82 to 1.04, p = 0.21) and allergic asthma (RR 0.66, 95% CI 0.24 to 1.86, p = 0.44). The risk of asthma/wheeze in offspring was significantly decreased in the subgroup analysis when:: (1) studies conducted in Europe (RR 0.69; 95% CI 0.53 to 0.89); (2) daily supplementary dose of n-3 LC-PUFA was at least 1200 mg (RR 0.69; 95% CI 0.55 to 0.88); (3) supplementation lasts from pregnancy to lactation period (RR 0.69; 95% CI 0.51 to 0.95). Furthermore, the risk of asthma/wheeze reduce 2% when daily supplemental dose of n-3 LC-PUFA was increased by 100 mg in the linear dose-response analysis model. CONCLUSIONS: Perinatal supplementation with n-3 LC-PUFA can reduce the incidence of asthma/wheeze and allergic asthma in children under certain conditions, and higher doses indicate better protective effects. Further studies are required to confirm the hypothesis of an association between n-3 LC-PUFA intake and childhood asthma/wheeze prevention.

Placenta percreta after Strassman metroplasty of complete bicornuate uterus: a case report.

BACKGROUND: A bicornuate uterus often results in infertility. While reconstructive procedures may facilitate pregnancy, spontaneous abortion or serious pregnancy complications may occur. We present a case of a bicornuate uterus with spontaneous conception after Strassman metroplasty; however, life-threatening complications during pregnancy occurred. CASE PRESENTATION: A 38-year-old woman with a history of infertility presented for prenatal care at 6 weeks of gestation. She had conceived spontaneously after four failed in vitro fertilization and embryo transfer (IVF-ET) procedures, Strassman metroplasty for a complete bicornuate uterus, and two postoperative IVF-ET pregnancies that ended in embryo arrest. This pregnancy was uneventful until the patient presented with massive vaginal bleeding at 28 weeks of gestation and was diagnosed with placenta previa and placenta percreta. Bleeding was controlled after emergency Caesarean section and delivery of a healthy neonate. However, severe adhesions were noted as well as a rupture along the metroplasty scar. Two days later, on removal of the intrauterine gauze packing, severe hemorrhage resumed, and the uterus did not respond to oxytocin, hemabate, or carbetocin. Emergency hysterectomy was required. CONCLUSIONS: Reconstructive surgical procedures for complete bicornuate uterus may allow patients to achieve spontaneous pregnancies. However, potential intrapartum complications include placenta implantation and postpartum hemorrhage, and the latter may be exacerbated as the uterus does not contract or respond to oxytocin or prostaglandin drugs. Patients should be counseled on the risks associated with pregnancy after Strassman metroplasty, and clinicians must be aware of potential severe complications.

Gene mutation and pedigree analysis of tetrahydrobiopterin deficiency in a Uygur family of China.

BACKGROUND: Tetrahydrobiopterin (BH4 ) deficiency is an autosomal recessive disorder, which is caused by an enzyme deficiency involved in its synthetic or metabolic pathways. Clinical symptoms may include microcephaly, hypoevolutism, severe ataxia, and seizures. The purposes of this study are to analyze the genotype-phenotype and the pedigree of the first case of BH4 deficiency in the Uygur of China. METHODS: (a) This patient received tandem mass spectrometry, urinary neopterin and biopterin analysis, and determination of dihydropteridine reductase (DHPR) activity in dried blood spots. (b) Blood DNA samples of this patient and her three family members were collected for gene sequencing and mutation analysis. RESULTS: (a) The basic urinary neopterin and biopterin were 1.07 mmol/mol Cr and 3.12 mmol/mol Cr, respectively, and biopterin percentage was 74.42%. The DHPR activity of this patient was 31.11% of normal control. (b) Sanger sequencing of PAH gene in this patient was negative but positive of her sister, which carries 2 heterozygous mutation c.781C>T and c.1238G>C. Next-generation sequencing on the patient identified a homozygous mutation in the quinoid dihydropteridine reductase (QDPR) gene at c.508G>A, which was confirmed by Sanger sequencing. CONCLUSION: (a) The patient was the first case of clinical diagnosis of BH4 deficiency in the Uighur. And there are two types of hyperphenylalaninemia (HPA) in the same family. (b) The mild HPA patient with severe nervous system damage should pay more attention to the BH4 deficiency. (c) Using next-generation sequencing technology can increase the mutation detection rate when the hereditary diseases are highly suspected in clinic.

Pregnancy outcomes in Chinese urban women at a very advanced maternal age.

AIM: To compare the maternal-fetal outcomes in Chinese urban women at the maternal age of 40 years with those aged between 35 and 39 years. MATERIALS AND METHODS: In this retrospective study, women in a single-center that delivered from January 1 to December 31, 2013, were included. The authors divided the subjects into two groups according to the age, and evaluated the obstetric history, delivery mode, incidence of obstetric diseases, and neonatal outcomes of each group. RESULTS: They enrolled 1,965 pregnant women in total. The women between 35 to 39 years of age reached 1,727 (87.9%), and the remaining 238 (12.1%) were women ≥ 40-years-old. The incidence rates of in vitro fertilization (IVF,p < 0.01), gestational diabetes mellitus (GDM) (p < 0.05), and hypertension (p < 0.05) for the elder group were higher than the younger group. Furthermore, women ≥ 40-years-old were associated with a higher rate of cesarean section (84.0% vs. 67.6%,p < 0.001) compared with the younger group, varying significantly on intrauterine infection (1.5% vs. 0.5%,p < 0.05), IVF (6.5% vs. 3.2%,p < 0.01), and maternal request (41.0% vs. 30.6%,p < 0.001). No significant differences in neonatal outcomes were found and no neonatal deaths were recorded for the two groups. CONCLUSIONS: These results showed an increase risk of pregnancy complications for the women giving birth at ≥ 40 years of age, yet most of them still carried a favorable pregnancy and neonatal outcome, similar to the younger women.

Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer.

BACKGROUND: Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development. METHODS: To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells. RESULTS: H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway. CONCLUSIONS: The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers.

Cardioprotection provided by Echinatin against ischemia/reperfusion in isolated rat hearts.

BACKGROUND: This study evaluated the protective effect of Echinatin against myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: The effect of Echinatin on cardiac function in rats subjected to I/R was demonstrated through improved Langendorff retrograde perfusion technology. Adult Sprague-Dawley rats were randomly divided into five groups, and myocardial infarct size was macroscopically estimated through 2,3,5-triphenyltetrazolium chloride staining. The coronary effluent was analyzed for the release of lactate dehydrogenase (LDH) and creatine kinase (CK) to assess the degree of cardiac injury. The concentrations of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined along with superoxide dismutase (SOD) activity using ELISA. Finally, cardiomyocyte apoptosis analysis was conducted with POD, an in situ cell death detection kit. RESULTS: Echinatin (0.5 and 2.5 µg/mL) pretreatment enhanced the maximum up/down rate of the left ventricular pressure (±dp/dtmax), improved the heart rate, increased the left ventricular developed pressure (LVDP), enhanced the coronary flow, and reduced the CK and LDH levels in the coronary flow of the treated group compared with the I/R group. Echinatin limited the contents of CK and LDH, improved the LVDP, reduced the contents of MDA, IL-6, and TNF-α, and increased the SOD activity. The infarct size and cell apoptosis in the hearts of the rats in the Echinatin-treated group were smaller and lower, respectively, than those in the hearts of the rats in the I/R control group. CONCLUSION: Echinatin exerts a protective effect against I/R-induced myocardial injury on hearts. This effect may be attributed to the antioxidant and anti-inflammatory activities of this compound.

Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-ß1/Smads signaling pathway mediated Snail/E-cadherin expression.

BACKGROUND: Resveratrol extracted from grape has been an ideal alternative drug in the therapy of different cancers including colorectal cancer (CRC). Since the underlying mechanisms of resveratrol on the invasion and metastasis of CRC have not been fully elucidated, and epithelial-to-mesenchymal transition (EMT) is a key process associated with the progression of CRC, here we aimed to investigate the potential mechanism of resveratrol on the inhibition of TGF-ß1-induced EMT in CRC LoVo cells. METHODS: We investigated the anticancer effect of resveratrol against LoVo cells in vitro and in vivo. In vivo, the impact of resveratrol on invasion and metastasis was investigated by mice tail vein injection model and mice orthotopic transplantation tumor model. In vivo imaging was applied to observe the lungs metastases, and hemaoxylin-eosin (HE) staining was used to evaluate metastatic lesions. In vitro, impact of resveratrol on the migration and invasion of LoVo cells was evaluated by transwell assay. Inhibition effect of resveratrol on TGF-ß-induced EMT was examined by morphological observation. Epithelial phenotype marker E-cadherin and mesenchymal phenotype marker Vimentin were detected by western blot and immunofluorescence. Promoter activity of E-cadherin was measured using a dual-luciferase assay kit. mRNA expression of Snail and E-cadherin was measured by RT-PCR. RESULTS: We demonstrated that, resveratrol inhibited the lung metastases of LoVo cells in vivo. In addition, resveratrol reduced the rate of lung metastases and hepatic metastases in mice orthotopic transplantation. In vitro, TGF-ß1-induced EMT promoted the invasion and metastasis of CRC, reduced the E-cadherin expression and elevated the Vimentin expression, and activated the TGF-ß1/Smads signaling pathway. But resveratrol could inhibit the invasive and migratory ability of LoVo cells in a concentration-dependent manner, increase the expression of E-cadherin, repress the expression of Vimentin, as well as the inhibition of TGF-ß1/Smads signaling pathway. Meanwhile, resveratrol reduced the level of EMT-inducing transcription factors Snail and the transcription of E-cadherin during the initiation of TGF-ß1-induced EMT. CONCLUSIONS: Our new findings provided evidence that, resveratrol could inhibit EMT in CRC through TGF-ß1/Smads signaling pathway mediated Snail/E-cadherin expression, and this might the potential mechanism of resveratrol on the inhibition of invasion and metastases in CRC.

The degradation of kinesin-like calmodulin binding protein of D. salina (DsKCBP) is mediated by the ubiquitin-proteasome system.

Kinesin-like calmodulin binding protein (KCBP) is a member of kinesin-14 subfamily with unconventional domains distinct from other kinesins. This unique kinesin has the myosin tail homology 4 domain (MyTH4) and band4.1, ezrin, radixin and moesin domain (FERM) at the N-terminal which interact with several cytoskeleton proteins. Although KCBP is implicated in several microtubule-related cellular processes, studies on the KCBP of Dunaliella salina (DsKCBP) have not been reported. In this study, the roles of DsKCBP in flagella and cytoskeleton were investigated and the results showed that DsKCBP was present in flagella and upregulated during flagellar assembly indicting that it may be a flagellar kinesin and plays a role in flagellar assembly. A MyTH4-FERM domain of the DsKCBP was identified as a microtubule and actin interacting site. The interaction of DsKCBP with both microtubules and actin microfilaments suggests that this kinesin may be employed to coordinate these two cytoskeleton elements in algal cells. To gain more insights into the cellular function of the kinesin, DsKCBP-interacting proteins were examined using yeast two-hybrid screen. A 26S proteasome subunit Rpn8 was identified as a novel interacting partner of DsKCBP and the MyTH4-FERM domain was necessary for the interaction of DsKCBP with Rpn8. Furthermore, the DsKCBP was polyubiquitinated and up-regulated by proteasome inhibitor and degraded by ubiquitin-proteasome system indicating that proteasome is related to kinesin degradation.

Labor induction in term gravidas with prelabor rupture of membranes and unfavorable cervixes: Oxytocin versus vaginal misoprostol.

OBJECTIVE: To compare maternal and neonatal outcomes between oxytocin and vaginal misoprostol induction in women with term prelabor rupture of membranes (PROM) and unfavorable cervixes. METHODS: In this retrospective study, 589 pregnant women with term singleton fetuses in cephalic presentation, reactive nonstress tests, PROM of 2-24 h duration, Bishop score <6, and no previous uterine surgery were reviewed and divided into oxytocin (n = 301) and misoprostol (n = 288) groups. The primary outcomes were the rate of vaginal delivery and delivery within 24 h. RESULTS: After 24 h of induction, the misoprostol group showed a significantly higher proportion of vaginal delivery (64.6% vs. 49.5%, P < 0.001) and a lower cesarean section delivery rate (11.5% vs. 25.2%, P < 0.001) than the oxytocin group. More primiparas in the misoprostol group achieved vaginal delivery within 24 h than in the oxytocin group (60.5% vs. 45.4%, P = 0.001). Among primiparas, the misoprostol group had a significantly lower cesarean delivery rate (12.6% vs. 27.5%, P < 0.001). CONCLUSION: Vaginal misoprostol induction in term PROM gravidas with unfavorable cervixes was associated with lower cesarean section and higher vaginal delivery rates within 24 h than oxytocin infusion. Vaginal misoprostol and oxytocin infusion had similar maternal and neonatal outcomes.

Evaluating the application of the 2009 Institute of Medicine gestational weight gain guidelines on pregnant Chinese women.

BACKGROUND: The 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines were initially developed for pregnant women in the United States. OBJECTIVE: This study aimed to investigate whether the IOM guidelines were suitable for pregnant Chinese women. METHODS: A retrospective cohort study comprising 20,593 singleton pregnant women was conducted at the Beijing Obstetrics and Gynaecology Hospital (1 January 2018 to 31 December 2019). Applicability was evaluated by comparing the GWG corresponding to the lowest point of the predicted composite risk curve with the 2009 IOM GWG Guidelines. The IOM Guidelines serve as the standard for the GWG categories and the pre-pregnancy body mass index. An exponential function model was used to fit the weight gain during pregnancy and the probability of caesarean section, preterm birth, small for gestational age, and large for gestational age. A quadratic function model was used to fit the combined probability of the above-mentioned adverse pregnancy outcomes. The applicability of the IOM guidelines was evaluated by comparing the weights corresponding to the lowest predicted probability with the GWG range recommended by the IOM guidelines. RESULTS: According to the 2009 IOM GWG Guidelines, 43% of the women achieved adequate weight, almost 32% gained excessive weight, and 25% gained inadequate weight. The GWG range proposed by the IOM included the lowest predicted probability value for underweight women and exceeded the lowest predicted probability for normal weight, overweight, and obese women. CONCLUSIONS: The 2009 IOM guidelines were suitable for Chinese women whose pre-pregnancy body mass index was classified as underweight. The guidelines were not suitable for normal, overweight, or obese pre-pregnancy body mass index classifications. Therefore, based on the above evidence, the 2009 IOM guidelines are not suitable for all Chinese women.

The progress on the relationship between gut microbiota and immune checkpoint blockade in tumors.

Immune checkpoint blockade (ICB) has emerged as a promising immunotherapeutic approach for the treatment of various tumors. However, the efficacy of this therapy is limited in a subset of patients, and it is important to develop strategies to enhance immune responses. Studies have demonstrated a critical role of gut microbiota in regulating the therapeutic response to ICB. Gut microbiota composition, diversity, and function are mediated by metabolites, such as short-chain fatty acids and secondary bile acids, that interact with host immune cells through specific receptors. In addition, gut bacteria may translocate to the tumor site and stimulate antitumor immune responses. Therefore, maintaining a healthy gut microbiota composition, for instance through avoiding the use of antibiotics or probiotic interventions, can be an effective approach to optimize ICB therapy. This review summarizes the current understanding of the microbiota-immunity interactions in the context of ICB therapy, and discusses potential clinical implications of these findings.

Study on Mechanism of Yiqi Yangyin Jiedu Recipe Inhibiting Triple Negative Breast Cancer Growth: A Network Pharmacology and In Vitro Verification.

Background: The present study explores the potential mechanism of Yiqi yangyin jiedu Recipe (YQYYJDR) on triple negative breast cancer via adopting network pharmacology and experimental validation. Materials and Methods: The potential active compounds and target genes of YQYYJDR were screened out from TCMSP database with OB ≥ 30% and DL index ≥ 0.18. The potential pathways and function enrichment were identified from Metascape website. MDA-MB-231 and MDA-MB-468 cells were tested for cell viability, invasion, and apoptosis by in vitro and in vivo experiments. Results: A total of 153 bioactive compounds and 281 target genes of YQYYJDR were retrieved from TCMSP database. The top 5 enrichment pathways of YQYYJDR target genes include pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, proteoglycans in cancer, IL-17 signaling pathway, and platinum drug resistance. 65 target genes were included in the pathway of cancer. Biological function enrichment analysis of 65 genes showed YQYYJDR inhibited tumor growth mainly through apoptotic pathway. In vitro experiments showed that YQYYJDR could inhibit the proliferation and invasion of MDA-MB-231 and MDA-MB-468 cells, arrest cells in S stage, and induce cell apoptosis. YQYYJDR upregulated BAX, caspase3, and cleaved caspase3 expression and downregulated BCL2 expression. In vivo experiments showed that YQYYJDR could inhibit tumor growth. Conclusions: In this study, network pharmacology and experiment were used to explore the mechanism of YQYYJDR on triple negative breast cancer. In vitro and in vivo experiments showed that YQYYJDR could inhibit the growth of triple negative breast cancer and induce cell apoptosis. Apoptosis pathway plays a significant role in the treatment of triple negative breast cancer.

Role of ARRB1 in prognosis and immunotherapy: A Pan-Cancer analysis.

Background: ß-arrestin1 (ARRB1), was originally identified as a multifunctional adaptor protein. Although ARRB1 has recently been shown to also play an important role in tumor growth, metastasis, inflammation, and immunity, its relationship with distinct tumor types and the tumor immune microenvironment remains unclear. Methods: We analyzed the ARRB1 expression profile and clinical characteristics in 33 cancer types using datasets from The Cancer Genome Atlas (TCGA) database. Clinical parameters such as patient survival, tumor stage, age, and gender were used to assess the prognostic value of ARRB1. The Human Protein Atlas (HPA) database was used to explore ARRB1 protein expression data. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration. Furthermore, putative correlations between ARRB1 and tumor-infiltrating immune cells, the signatures of T-cell subtypes, immunomodulators, the tumor mutation burden (TMB), Programmed cell death ligand 1 (PD-L1), and microsatellite instability (MSI) were also explored. Gene functional enrichment was determined using GSEA. GSE40435 and GSE13213 cohorts were used to validate the correlation of ARRB1 with KIRC and LUAD clinicopathological parameters. Finally, the relationship between ARRB1 and immunotherapeutic responses was assessed using three independent immunotherapy cohorts, namely, GSE67501, GSE168204, and IMvigor210. Results: We found that ARRB1 expression levels were lower in 17 tumor tissues than in the corresponding normal tissues. We further found that ARRB1 expression was significantly correlated with tumor stage in BRCA, ESCA, KIRC, TGCT, and THCA, while in some tumors, particularly KIRC and LUAD, ARRB1 expression was associated with better prognosis. ARRB1 expression was also positively correlated with the stromal score or the immune score in some tumors. Regarding immune cell infiltration, ARRB1 expression in DLBC was positively correlated with M1 macrophage content and negatively correlated with B-cell infiltration. Additionally, there was a broad correlation between ARRB1 expression and three classes of immunomodulators. Furthermore, high ARRB1 expression levels were significantly correlated with some tumor immune-related pathways. Finally, ARRB1 expression was significantly associated with MSI, PD-L1, and TMB in some tumors and with the efficacy of immune checkpoint inhibitors (ICIs) in melanoma. Conclusion: ARRB1 has prognostic value in malignant tumors, especially in KIRC and LUAD. At the same time, ARRB1 was closely correlated with the tumor immune microenvironment and indicators of immunotherapy efficacy, indicating its great potential as a reliable marker for predicting the efficacy of immunotherapy.

The cuproptosis-related gene signature serves as a potential prognostic predictor for ovarian cancer using bioinformatics analysis.

Background: Studies have shown that copper is involved in the tumorigenesis and development of ovarian cancer. In this work, we aimed to build a prognostic classification system associated with cuproptosis to predict ovarian cancer prognosis. Methods: Information of ovarian cancer samples were acquired from The Cancer Genome Atlas (TCGA)-ovarian cancer and GSE26193 dataset. Cuproptosis-related genes were screened from previous research. ConsensusClusterPlus was applied to determine molecular subtypes, which were evaluated by tumor immune microenvironment analysis, TIDE algorithm, and functional enrichment analysis. Furthermore, limma analysis and univariate Cox analysis were used to construct a cuproptosis-related prognostic signature for ovarian cancer. Univariate and multivariate Cox regression analyses were used to analyze the independence of clinical factors and model. Results: A total of 15 genes related to cuproptosis were identified, and 2 clusters (C1 and C2) were determined. C1 had a better survival outcome, less advanced stage, enhanced immune infiltration, was more sensitive to immunotherapy, and showed enrichment in tricarboxylic acid (TCA)-related pathways. An 8 cuproptosis-associated gene signature was constructed, and the signature was verified in the GSE26193 dataset. A higher risk score of the cuproptosis-related gene signature was significantly correlated with worse overall survival (OS) (P<0.0001), which was validated in GSE26193 dataset successfully. Cox survival analysis showed that risk score was an independent predictor [hazard ratio (HR) =2.66, P<0.001]. Functional enrichment and tumor immune microenvironment analyses showed that high-risk patients tended to have immunologically sensitive tumors. Conclusions: The cuproptosis-related gene signature may serve as a potential prognostic predictor for ovarian cancer patients and may offer novel treatment strategies for ovarian cancer.

Cesarean section and pregnancy outcomes of preterm premature rupture of membranes under different fertility policies in China.

BACKGROUND: The aim of the present study was to compare the outcomes of pregnancies complicated by preterm premature rupture of membranes (PPROM) in China. METHODS: The present study was a single-center retrospective study of women admitted to Beijing Obstetrics and Gynecology Hospital in 2012, 2014, and 2017. Deliveries at <24 and >37 weeks, fatal deformities, stillbirths, and multiple pregnancies were excluded. Pregnancies were divided into 24-27+6, 28-33+6, and 34-36+6 weeks according to weeks of gestation in each year. In total, 1,178 pregnancies complicated by PPROM were analyzed in terms of incidence rate, risk factors, delivery mode, and neonatal outcomes. RESULTS: The rate of PPROM was 3.11% in 2012, 2.35% in 2014, and 2.4% in 2017; the difference was significant (P<0.001). Age [odds ratio (OR): 1.046, P<0.001], intrauterine infection (OR: 2.087, P=0.007), and vaginitis (OR: 1.812, P=0.039) were risk factors for PPROM. In all 3 years, patients with PPROM tended to choose vaginal delivery rather than cesarean section (CS) delivery (68.9% in 2012, P<0.001; 76.5% in 2014, P<0.001; 69.3% in 2017, P<0.001), and the rate of vaginal deliveries in 2014 was higher than that in 2012 and 2017 (P=0.027). Indications for PPROM at 34-36+6 weeks varied significantly among the 3 years (P<0.001). No significant difference was found in body weight, body length, and Apgar score at 1, 5, and 10 min; however, there was a significant difference in Apgar score after 1 min at 28-33+6 weeks (P=0.012). CONCLUSIONS: The incidence rate of PPROM at our single center varied between 2012, 2014, and 2017. Risk factors for pregnancies complicated by PPROM include age, intrauterine infection, and vaginitis. The rate of CS delivery varied, and breech/transverse presentation was the major indication for patients with PPROM at 34-36+6 weeks.