Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Objective:To investigate the protective effect and mechanism of 4-octyl itaconate(4-OI)on vascular endothelial function in diabetic mice,since endothelial dysfunction is the key and initial factor for vascular complications in diabetes.Methods:The db/db mice were used to establish a mouse model of diabetes,and high glucose(HG)-induced human umbilical vein endothelial cells(HUVECs)were used to establish a cell model of diabetes.After 4-OI treatment,HE staining,Masson staining,and reticular fiber staining were used to observe pathological changes of the thoracic aorta in the control group,the model group,and the intervention group;Western blot was used to measure the expression of α-smooth muscle actin(α-SMA),a marker for endothelial fibrosis;immuno-fluorescence assay was used to measure the expression levels of Bcl-2-associated X protein(BAX)and B-cell lymphoma-2(Bcl-2)in the thoracic aorta of mice in the control group,the model group,and the intervention group;immunoblotting was used to observe the effect of 4-OI intervention on the expression of BAX,Bcl-2,and the proteins associated with the cytochrome C(CytC)/cysteinyl aspartate specific proteinase(caspase)pathway in HG-induced HUVECs.Results:The results showed that 4-OI could significantly improve vascular endothelial dysfunction in db/db diabetic mice.Compared with the model group,the intervention group had a significant increase in the expression of Bcl-2(0.73±0.07 vs.0.52±0.04,F=49.380,P=0.009)and a significant reduction in the expression of BAX(1.41±0.14 vs.1.89±0.12,F=37.270,P=0.008)after 4-OI treatment.In the cell model of HUVECs induced by HG,compared with the high glucose group,the intervention group had a sig-nificant increase in the expression of Bcl-2(1.22±0.04 vs.0.81±0.09,F=75.410,P<0.001)and a significant reduction in the expres-sion of BAX(0.83±0.04 vs.1.12±0.04,F=268.100,P<0.001)after 4-OI treatment,as well as significant reductions in the expres-sion of CytC(0.61±0.03 vs.1.01±0.03,F=234.000,P<0.001),caspase-9(0.62±0.03 vs.1.04±0.04,F=164.300,P<0.001),and caspase-3(0.92±0.06 vs.1.74±0.04,F=424.100,P<0.001).Conclusion:In conclusion,4-OI inhibits vascular endothelial cell apoptosis in diabetic mice by affecting the expression of the CytC/Caspase pathway factors,thereby improving vascular endothelial dys-function in diabetes.

Objective:To verify the prognostic significance of the tumor regression grade (TRG) for muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC) after neoadjuvant chemotherapy.Methods:The data of 70 MIBC patients treated with gemcitabine combined with cisplatin neoadjuvant chemotherapy and RC in Sun Yat-sen University Cancer Center between July 2016 to November 2021 were retrospectively reviewed. There were 65 males and 5 females, with an average age(59.79±10.56)years old. The patients accepted transurethral resection of bladder tumor (TURBT) specimens before neoadjuvant chemotherapy. Clinicopathological characteristics of patients were recorded and TRG was assessed. TRG evaluation criteria: TRG 1 was defined as no cancer residue, TRG 2 was defined as the proportion of residual cancer area to tumor bed area <50%, and TRG 3 was defined as the proportion of residual cancer area to the area of the tumor bed ≥ 50%. Chi-square test or Fisher's exact test were used to compare the relationship between patients' clinicopathological characteristics and TRG. The relationship between post-neoadjuvant therapy tumor and node(ypTN)stage, and survival, including overall survival(OS)and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis. The pathologically locally descending disease was defined as (ypT < T 2 and ypN=N 0) and pathologically locally advanced disease was defined as (ypT≥T 2 and/or ypN ≥N 1). Cox regression was used for univariate and multivariate analysis of OS and RFS. Results:Chi-square test or Fisher exact test analysis showed TRG was significantly associated with ypT stage ( P < 0.001), ypN stage ( P = 0.002), lympho-vascular invasion ( P<0.001) and variant histology ( P<0.001). The OS of patients with TRG 1, TRG 2 and TRG 3 were 20.5(10.3, 31.8), 17.0(11.0, 30.8)and 15.0(11.0, 26.0) months, respectively, and the difference was significantly different( P = 0.037). The RFS of patients with TRG 1, TRG 2 and TRG 3 were 15.0(8.3, 25.5), 15.0(8.0, 27.0)and 11.0(4.5, 25.5) months, respectively, and the difference was significantly different ( P=0.029). There were significant differences between patients with pathologically locally descending disease and locally advanced disease in OS [18.5(10.3, 30.8)vs.15.0(11.0, 27.3)months, P = 0.013] and RFS [14.0(8.0, 24.0)vs. 11.5(8.0, 26.8)months, P = 0.012]. Among patients with locally advanced pathology, the OS was 19.5(11.0, 32.5)months for patients with TRG ≤2, 13.5(10.8, 26.0)months for patients with TRG 3( P=0.140). The RFS was 12.0(8.0, 31.0)months for those patients with TRG ≤2 and 11.0(6.0, 26.0)months for those patients with TRG 3( P = 0.180). Cox univariate analyses showed that patients with TRG 3 were associated with decreased OS ( HR = 6.043, 95% CI 1.170-31.213, P = 0.032) and RFS ( HR = 6.354, 95% CI 1.231-31.802, P = 0.027). Conclusions:This study showed that TRG was correlated with OS and RFS among patients. The patients who had the higher TRG had the worse prognosis. It was confirmed that TRG predicted the prognosis of patients undergoing radical cystectomy after neoadjuvant chemotherapy. Therefore, TRG assessment is recommend in pathology report for patients who had radical cystectomy after neoadjuvant chemotherapy.

To study the chemical constituents of petroleum ether extract from the stems and leaves of Humulus scandens (family of Moraceae), fifteen compounds were isolated from the stems and leaves of H.scandens by silica gel, Sephadex LH-20, ODS, and preparative HPLC chromatography.The structures were identified by physicochemical data and spectroscopic method as tectochrysin (1), chrysin (2), 5-hydroxy-3, 4'', 6, 7-tetramethoxyflavone (3), (2S)-5-hydroxy-7, 8-dimethoxyflavanone (4), imperatorin (5), phellopterin (6), ethyl 4-hydroxy-3-(3''-methyl-2''-butenyl)benzoate (7), p-hydroxy-phenylpropionic acid (8), ethyl p-hydroxycinnamate (9), p-hydroxybenzaldehyde (10), anofinic acid (11), 5,6-dehydrokavain (12), physcion (13), olean-12-ene-3,?11-dione (14) and ergosta-4, 6, 8 (14), 22-tetraen-3-one (15), respectively.All compounds were isolated from this plant for the first time.

Objective:To evaluate the effectiveness and safety of coronavirus disease 2019 (COVID-19) vaccines for dialysis patients with chronic kidney disease.Methods:PubMed, Medline, Embase databases and CNKI, VIP, Wanfang databases were searched systematically. The deadline was April 25, 2022. The search terms included haemodialysis, peritoneal dialysis, vaccine, seroresponse, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main outcome included the positive rate after vaccination, antibody titer, antibody changes during follow-up, infection rate of SARS-CoV-2, hospitalization rate and mortality.Results:A total of 154 195 patients were analyzed in 26 studies. The results of meta-analysis showed that the positive rate of serum IgG antibody in patients with chronic kidney disease was 48% after the first dose of vaccine, 89% and 96% after the second dose and third dose, respectively. After vaccination with COVID-19 vaccines, there was no significant difference in serum antibody and titer between hemodialysis patients and peritoneal dialysis patients. However, compared with the healthy control group, the antibody positive rate and antibody titer of dialysis patients after vaccination were lower (both P<0.05). In the follow-up, the antibody positive rate at the third month decreased by 12% compared with at the first month, at the sixth month decreased by 15% compared with at the third month, and at the sixth month decreased by 20% compared with at the first month. The serum antibody positive rate after the third dose of vaccine increased by 38% ( RR=1.38, 95% CI 1.12-1.70, P<0.001), and the antibody titer increased significantly ( SMD=1.46, 95% CI 0.31-2.61, P<0.001). Although the vaccines could not reduce the infection rate of SARS-CoV-2 in dialysis patients, it could significantly reduce the hospitalization rate and mortality after infection. Conclusions:After vaccination with COVID-19 vaccines, dialysis patients can produce strong serum antibodies, which can reduce the hospitalization rate and mortality after SARS-CoV-2 infection. However, the duration of antibody is short and the titer level is low, so it is necessary to timely vaccinate booster vaccine dose to obtain stronger immunogenicity.

Due to the special geographical location and the complex ecosystem types, plateau wetlands play important ecological roles in water supply, greenhouse gas regulation and biodiversity preservation. Napahai plateau wetland is a special wetland type with low latitude and high altitude, and its microbial diversity was rarely studied. The diversity of microbial communities in the Napahai plateau wetland was analyzed using metagenomics method. Among the microbes detected, 184 phyla, 3 262 genera and 24 260 species belong to the bacterial domain, 13 phyla and 32 genera belong to the archaeal domain, and 13 phyla and 47 genera belong to the fungal domain. Significant differences in species diversity between soil and water were observed. Acidobacteria, Proteobacteria and Actinobacteria were dominant phyla in soil, while Proteobacteria and Bacteroides were dominant phyla in water. Since the carbon and nitrogen metabolism genes were abundant, the pathways of carbon fixation and nitrogen metabolism were analyzed. Calvin cycle, reductive tricarboxylic acid cycle and 3-hydroxypropionic acid cycle were the main carbon fixation pathways, while Proteobacteria, Chloroflexi, and Crenarchaeota were the main carbon-fixing bacteria group. As for the nitrogen cycle, nitrogen fixation and dissimilatory nitrate reduction were dominant in water, while nitrification and denitrification were dominant in soil. Proteobacteria, Nitrospirae, Verrucomicrobia, Actinobacteria, Thaumarchaeota and Euryarchaeota contributed to the nitrogen cycle. The study on microbial diversity of Napahai plateau wetlands provides new knowledge for the comprehensive management and protection of wetland environment in China.
Carbon ; Ecosystem ; Metagenomics ; Nitrogen ; Soil Microbiology ; Wetlands

The emergence of regular short repetitive palindromic sequence clusters (CRISPR) and CRISPR- associated proteins 9 (Cas9) gene editing technology has greatly promoted the wide application of genetically modified pigs. Efficient single guide RNA (sgRNA) is the key to the success of gene editing using CRISPR/Cas9 technology. For large animals with a long reproductive cycle, such as pigs, it is necessary to screen out efficient sgRNA
Animals ; CRISPR-Cas Systems/genetics* ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics* ; Gene Editing ; RNA, Guide/genetics* ; Swine

Objective:To compare the effect of SMOF lipids composed of soybean oil, medium chain triglycerides, olive oil, and fish oil with medium-long chain mixed fat emulsions(Lipofundin) on parenteral nutrition-associated cholestasis(PNAC) in premature infants.Methods:Clinical data were collected from premature infants hospitalized in the neonatal intensive care unit of Shanghai Children′s Hospital from January 2018 to December 2019 with gestational age ≤34 weeks, birth weight ≤2 000 g, and duration of parenteral nutrition ≥14 days.They were devided into SMOF lipid group and Lipofundin group, and the incidence of PNAC, neonatal necrotizing enterocolitis(NEC), bronchopulmonary dysplasia(BPD), retinopathy of prematurity(ROP), periventricular-intraventricular hemorrhage(PVH-IVH), late-onset sepsis and liver function were compared between two groups.Results:The incidence of PNAC in the SMOF lipid group was significantly lower than that in Lipofundin group( P=0.042). The average level of ALT and AST in SMOF lipid group were markedly lower than those in Lipofundin group( P<0.05). The time to reach full enteral feeding of SMOF lipid group was shorter than that of Lipofundin group( P=0.005). There was no significant difference in the incidence of NEC, BPD, ROP, PVH-IVH, and late-onset sepsis between two groups( P>0.05). Conclusion:Compared with lipofundin, SMOF lipid can reduce the incidence of PNAC in premature infants, and has no significant effect on the incidence of NEC, BPD, ROP, PVH-IVH and late-onset sepsis.

Objective:To study the early predictive value of urine neutrophil gelatinase-associated lipoprotein (NGAL) and kidney injury molecule-1 (KIM-1) for acute kidney injury (AKI) in neonates with severe asphyxia.Method:From January 2019 to June 2020, neonates with severe asphyxia admitted to our hospital within 6 hours after birth were enrolled in the study. The dynamic changes of urine NGAL and KIM-1 at admission, 24 h, 48 h and 1 w after birth were examined. Neonates were assigned into AKI group and non-AKI group according to the clinical practice guidelines for AKI issued by KDIGO (Kidney Disease: Improving Global Outcome). The sensitivity and specificity of NGAL and KIM-1 predicting AKI at different time points were evaluated using ROC curve and area under curve (AUC).Result:According to the diagnostic criteria of neonatal AKI, 9 cases were in the AKI group and 42 cases in the non-AKI group, and the incidence of AKI was 17.6%. Urine NGAL was significantly increased in AKI group at admission and 24 h after birth compared with the non-AKI group [(115.6±75.5) ng/ml vs. (49.8±29.0) ng/ml, (90.7±35.6) ng/ml vs. (55.6±30.7) ng/ml] ( P<0.05). No significant differences existed at 48 h and 1 w after birth between the two groups. At 24 h after birth, urine KIM-1 in the AKI group was significantly higher than the non-AKI group [(808.3±555.3) pg/ml vs. (318.4±234.0) pg/ml, P<0.05] and no significant differences existed between the two groups at admission, 48 h and 1 w after birth. The AUC of NGAL predicting AKI at admission, 24 h, 48 h and 1w after birth were 0.804 (95% CI 0.573~1.000), 0.792 (95% CI 0.580~1.000), 0.732 (95% CI 0.517~0.947) and 0.551(95% CI 0.371~0.730), respectively. The AUC of KIM-1 predicted AKI at admission, 24 h, 48 h and 1 w after birth was 0.860 (95% CI 0.676~1.000), 0.824 (95% CI 0.655~0.993), 0.768 (95% CI 0.622~0.914), 0.622 (95% CI 0.392~0.852), respectively. Conclusion:At admission, 24 h and 48 h after birth, urine NGAL and KIM-1, as kidney injury markers, may predict the occurrence of AKI after severe neonatal asphyxia.

Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.