Background::Polycystic ovarian syndrome (PCOS) is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility. There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques (ART).Methods::Infertile PCOS patients who underwent their first cycle of in vitro fertilization (IVF) in West China Second University Hospital, Sichuan University from January 2019 to December 2021 were included. Basic clinical and laboratory information of each individual were extracted. Unsupervised cluster analysis was performed. Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS. Results::Our analysis clustered women with PCOS into "reproductive", "metabolic", and "balanced" clusters based on nine traits. Reproductive group was characterized by high levels of testosterone (T), sex hormone-binding globulin (SHBG), follicular stimulation hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH). Metabolic group was characterized by high levels of body mass index (BMI), fasting insulin, and fasting glucose. Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters, except for SHBG. Compared with PCOS patients in reproductive and balanced clusters, those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation. Moreover, PCOS patients in the reproductive cluster had greater fresh embryo transfer (ET) cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster (odds ratio [OR] = 3.37, 95% confidence interval [CI]: 1.77-6.44, and OR = 6.19, 95% CI: 1.58-24.24, respectively). And compared with PCOS of metabolic cluster, PCOS of balanced cluster also had higher chance for fresh ET cancelation (OR = 2.83, 95% CI: 1.26-6.35).Conclusion::Our study suggested that PCOS patients in metabolic cluster may be associated with adverse reproductive outcomes and might need individualized treatment and careful monitoring before and during ART.

Objective:To evaluate the significance of the lumbar bowstring ratio (LBR) and sagittal spine-pelvis parameters in predicting postoperative neurogenic pain in adult patients with high-grade lumbar isthmic spondylolisthesis following spinal fusion surgery.Methods:A retrospective analysis was conducted on the clinical and imaging data of 95 adult patients with high-grade lumbar isthmic spondylolisthesis treated by spinal surgery at Xiangya Hospital of Central South University from August 2012 to January 2023. Each patient was followed for a minimum of six months. Participants were categorized into pain and non-pain groups based on the presence of persistent radicular pain (≥8 weeks) and a visual analogue scale (VAS) score of ≥3 postoperatively. The pain group comprised 15 patients (5 males, 10 females; mean age 55.47±6.42 years, range 46-71 years), while the non-pain group included 80 patients (20 males, 60 females; mean age 60.98±11.50 years, range 40-85 years). Clinical outcomes were assessed using the Oswestry Disability Index (ODI) and VAS scores. LBR was defined as the ratio of the vertical distance from the anterior convexity of the L 1-L 5 anterior longitudinal ligament to a line connecting the posterior superior margin of the L1 vertebra and the posterior margin of the S1 vertebra, to the distance between these two points. Spinal-pelvic parameters measured included pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), PT/SS ratio, and changes in LBR before and after surgery (ΔLBR). Statistical comparisons of demographic and imaging parameters were performed between the two groups, and variables showing significant differences were subjected to binary logistic regression analysis to identify independent risk factors for postoperative neurogenic pain. Results:All 95 patients achieved complete anatomical reduction of the dislocation without reported wound infections. Follow-up was completed at 7.68±2.98 months (range 6-12 months) postoperatively. Among the patients, 15 developed iatrogenic radicular pain. Postoperative complications included pulmonary infection (4 cases: 1 in the pain group, 3 in the non-pain group), cerebrospinal fluid leakage (8 cases: 2 in the pain group, 6 in the non-pain group), and delirium (5 cases: 2 in the pain group, 3 in the non-pain group). No significant differences were observed in demographic data between the groups ( P>0.05). Both groups demonstrated significant improvements in ODI (pain group Z=-3.413, P=0.001; non-pain group Z=-7.772, P<0.001) and VAS scores (pain group Z=-3.426, P=0.001; non-pain group Z=-7.838, P<0.001) at the 6-month follow-up compared to preoperative values. Significant differences were found between the pain and non-pain groups in PI ( t=3.315, P=0.004), PT ( t=5.087, P<0.001), SS ( t=7.431, P<0.001), LL ( t=3.764, P<0.001), PT/SS ( t=7.267, P<0.001), LBR ( t=6.455, P<0.001), and ΔLBR ( Z=5.362, P<0.001) before and after surgery. Binary logistic regression analysis identified smaller preoperative PT/SS [ OR=0.760, 95% CI(0.601, 0.961), P=0.022] and larger preoperative LBR [ OR=5.721, 95% CI (1.068, 30.634), P=0.042] as independent risk factors for postoperative neurogenic pain. Conclusion:High LBR and reduced PT/SS are significant risk factors for neurogenic pain following complete discectomy and fusion in adult patients with high-grade lumbar isthmic spondylolisthesis. For such patients, careful consideration is warranted regarding anatomical complete reduction during surgical intervention.

Objective:To investigate the effects of teaching reform to strengthen the integration of basic medicine and clinical medicine by analyzing the scores of the National Medical Licensing Examination from 2014 to 2018.Methods:Through the improvement of the training program, the establishment of subject integration courses, the standardization of case teaching mode and the establishment of comprehensive medical experiment courses, the teaching reform of the combination of basic medicine and clinical medicine was carried out. The differences in the scores of the National Medical Licensing Examination between the students from Dalian University and those from the whole country were compared, including the average total scores, the passing rates, the average mastery rates of the basic medicine, and the average mastery rates of the cognitive level of the basic medicine.Results:In 2014, 2015 and 2016, the average total scores of the students from Dalian University were 384.70±53.62, 395.45±50.49, and 401.43±50.88, respectively, which were lower than those from the whole country (396.15±58.85, 400.78±56.88, and 405.15±58.06). The average mastery rates of the basic medicine of the students from Dalian University were 56.28%, 62.45%, and 64.92%, respectively, lower than those from the whole country (58.41%, 62.46%, and 65.36%). The average mastery rates of the basic medicine of the students form Dalian University from 2014 to 2016 were lower than those from the whole country, and those were higher in 2017 to 2018 than the whole country. The average total scores of the students form Dalian University in 2017 and 2018 were 397.11 and 400.26 ± 61.15, respectively, higher than those from the whole country (388.91 and 397.01±58.35). The average mastery rates of the basic medicine of the students form Dalian University were 61.53% and 59.85%, respectively, higher than those from the whole country (58.64% and 58.38%). The total passing rates of the students from Dalian University in 2014 and 2016 were 91.11% and 72.73%, respectively, lower than those from the whole country (91.18% and 73.75%), while in 2015, 2017 and 2018 those were 76.47%, 77.78%, and 77.59%, respectively, all higher than those from the whole country (73.59%, 74.29%, and 76.89%). All the data showed a trend of increase with the teaching reform process.Conclusion:Strengthening the teaching reform of the combination of basic medicine and clinical medicine during the learning stage of basic medicine could improve students' learning interest and attention to the basic medical knowledge, strengthen the understanding of the relevance of basic medicine to clinical medicine, and play a positive role in the cultivation of medical students' post competency and the achievement of the goal of training applied medical talents.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1β, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.
Animals ; Cattle ; Male ; Rats ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Body Weight ; Codonopsis/chemistry* ; Interleukin-6/blood* ; NF-kappa B/genetics* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Plant Extracts/therapeutic use* ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 2/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/pharmacology*

COVID-19 ; Coronavirus Nucleocapsid Proteins ; Humans ; Nucleocapsid Proteins ; Phosphoproteins ; SARS-CoV-2

The color of Rubus chingii was characterized by digital method, and the content of water extract, alcohol extract, total flavonoids, total polysaccharides, total polyphenols, ellagic acid, linden glycoside, kaophenol-3-O-rutin were determined. Correlation regression was used to analyze the correlation between color and composition. The results showed that L~* was positively correlated with total polyphenols, kaophenol-3-O-rutin and tilide, and moderately positively correlated with total flavones, ellagic acid and aqueous extracts. The a~* value was negatively correlated with total polyphenols, kaophenol-3-O-rutin, and linden glycosides, while was moderately correlated with total flavones, aqueous extracts, and ellagic acid. The b~* value was negatively correlated with the water extract, and moderately correlated with the content of total polyphenols, total polysaccharides, alcohol extract and kaophenol-3-O-rutin, which showed that R. chingii mature color had a significant correlation with material composition in the process of dynamic change. According to the law of dynamic change in the color and quality indexes, it is determined that the appropriate harvest time is in late April to May 1, while the fruit is not turn yellow. The agronomic traits related to fruit was(12.49±0.56) mm in diameter,(14.25±1.19)mm in height,(1.20±0.14) g in weight, the chroma L~* value was 52.87±3.14,a~* value was 2.01±1.58, b~* values was 28.31±3.88. The results lay a foundation for establishing an objective quantitative evaluation model of R. chingii color from experience.
Flavonoids ; Fruit ; Glycosides ; Plant Extracts ; Rubus

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.
Apoptosis Regulatory Proteins ; Cell Proliferation ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell ; genetics ; MicroRNAs ; Prognosis