Prevalence, Predictors, and Outcomes of Pulmonary Hypertension in Patients with Lupus Nephritis.

Background and Objectives: This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Materials and Methods: Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. Results: A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 compared to those with an eGFR ≥ 30 mL/min/1.73 m2 (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01-4.00; p = 0.047) and renal events (HR: 2.07; 95% CI: 1.04-4.12; p = 0.039). Conclusions: PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.

Biomimetic "Gemini nanoimmunoregulators" orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages.

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic "Gemini nanoimmunoregulators" was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The "Gemini nanoimmunoregulators" PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

Using organoids to investigate human endometrial receptivity.

The human endometrium is only receptive to an implanting blastocyst in the mid-secretory phase of each menstrual cycle. Such time-dependent alterations in function require intricate interplay of various factors, largely coordinated by estrogen and progesterone. Abnormal endometrial receptivity is thought to contribute to two-thirds of the implantation failure in humans and therefore significantly hindering IVF success. Despite the incontrovertible importance of endometrial receptivity in implantation, the precise mechanisms involved in the regulation of endometrial receptivity remain poorly defined. This is mainly due to a lack of proper in vitro models that recapitulate the in vivo environment of the receptive human endometrium. Organoids were recently established from human endometrium with promising features to better mimic the receptive phase. Endometrial organoids show long-term expandability and the capability to preserve the structural and functional characteristics of the endometrial tissue of origin. This three-dimensional model maintains a good responsiveness to steroid hormones in vitro and replicates key morphological features of the receptive endometrium in vivo, including pinopodes and pseudostratified epithelium. Here, we review the current findings of endometrial organoid studies that have been focused on investigating endometrial receptivity and place an emphasis on methods to further refine and improve this model.

Biomimetic Nano-Immunoactivator via Ionic Metabolic Modulation for Strengthened NIR-II Photothermal Immunotherapy.

Reprogramming the immunologically "cold" environment of solid tumors is currently becoming the mainstream strategy to elicit powerful and systemic anticancer immunity. Here, a facile and biomimetic nano-immunnoactivator (CuS/Z@M4T1 ) is detailed by engineering a Zn2+ -bonded zeolitic imidazolate framework-8 (ZIF-8) with CuS nanodots (NDs) and cancer cell membrane for amplified near-infrared-II (NIR-II) photothermal immunotherapy via Zn2+ metabolic modulation. Taking advantage of the NIR-II photothermal effect of CuS NDs and the acidic responsiveness of ZIF-8, CuS/Z@M4T1 rapidly causes intracellular Zn2+ pool overload and disturbs the metabolic flux of 4T1 cells, which effectively hamper the production of heat shock proteins and relieve the resistance of photothermal therapy (PTT). Thus, amplified immunogenic cell death is evoked and initiates the immune cascade both in vivo and in vitro as demonstrated by dendritic cells maturation and T-cell infiltration. Further combination with antiprogrammed death 1 (aPD-1) achieves escalated antitumor efficacy which eliminates the primary, distant tumor and avidly inhibits lung metastasis due to cooperation of enhanced photothermal stimulation and empowerment of cytotoxic T lymphocytes by aPD-1. Collectively, this work provides the first report of using the intrinsic modulation property of meta-organometallic ZIF-8 for enhanced cancer photoimmunotherapy together with aPD-1, thereby inspiring a novel combined paradigm of ion-rich nanomaterials for cancer treatment.

Low-Operating-Voltage Two-Dimensional Tin Perovskite Field-Effect Transistors with Multilayer Gate Dielectrics Based on a Fluorinated Copolymer.

The fabrication of organic-inorganic perovskite field-effect transistors (FETs) with polymer gate dielectrics is challenging because of the solvent corrosion and wettability issues at interfaces. A few polymers have been integrated into perovskite transistors; however, these devices have high operating voltages due to low dielectric constants. Herein, poly(vinylidenefluoride-co-trifluoroethylene) (PVDF-TrFE) with a high dielectric constant is introduced into bottom-gate phenylethylammonium tin iodide perovskite [(PEA)2SnI4] FETs. Polytetrafluoroethylene (PTFE) and cross-linked poly(4-vinylphenol) (PVP) (CL-PVP) are used to address the issues of solvent corrosion and wettability. We design the PVDF-TrFE/PTFE and PVDF-TrFE/PTFE/CL-PVP dielectric layers, where the ferroelectric properties of PVDF-TrFE are reduced by PTFE. The (PEA)2SnI4 FETs operate at relatively low gate voltages, exhibiting good overall performance with average hole mobilities of 0.42 and 0.36 cm2 V-1 s-1. Our findings provide a feasible strategy for constructing low-operating-voltage perovskite FETs with large-dielectric-constant ferroelectric polymers as gate dielectrics by a solution processing technique.

Two-Dimensional Layered Simple Aliphatic Monoammonium Tin Perovskite Thin Films and Potential Applications in Field-Effect Transistors.

Two-dimensional (2D) layered organic-inorganic perovskites have great potential for fabricating field-effect transistors due to their unique structure that enables the horizontal transport of charge carriers in metal-halide octahedra, resembling the transport behavior in semiconducting channels. Their electronic band structures are mainly dominated by the metal-halide octahedra, which eventually determine the optical and electrical characteristics, whereas organic cations have no direct contributions but would impact the electronic structures via distorting the octahedra. So far, high performance has been achieved in 2D Sn perovskites compared to their Pb counterparts because the intrinsic differences of Sn promote transport properties. The champion hole mobility has been obtained in single-ring aromatic phenylethylammonium tin iodide perovskite [(PEA)2SnI4]. However, simple aliphatic monoammonium tin perovskites and their device applications have rarely been reported. Herein, 2D layered n-butylammonium tin iodide perovskite [(BA)2SnI4] thin films have been synthesized by a spin-coating approach. A structural phase transition occurs at about 225 K in the films, accompanied by the changes in the photoluminescence peak and exciton binding energy. Longitudinal optical (LO) phonons are found to govern the scattering of charge carriers and excitons via the Fröhlich interactions in the temperature range 77-300 K. The first-principles calculations predict that the perovskite has excellent transport characteristics comparable to those of molybdenum disulfide (MoS2) and methylammonium lead iodide perovskite (MAPbI3). The (BA)2SnI4 thin film field-effect transistors constructed on polymer dielectrics with a maximum hole mobility of 0.03 cm2 V-1 s-1 in ambient conditions have been successfully demonstrated for the first time. Our findings not only offer a deep insight into the physical properties of 2D layered aliphatic monoammonium tin perovskite thin films but also provide important experimental and theoretical guidance for their potential applications in lateral-type flexible optoelectronic devices.

Evaluation of the accuracy of colposcopy in detecting high-grade squamous intraepithelial lesion and cervical cancer.

PURPOSE: The primary aim of this study was to evaluate the diagnostic accuracy of colposcopy in identifying high-grade squamous intraepithelial lesion or worse (HSIL+) and the characteristic performance of colposcopic images with various severity levels of cervical lesions. METHODS: The medical records from 1828 women who underwent colposcopy at Affiliated Hospital of Tongji University from February 2016 to March 2019 were reviewed. Human papilloma virus (HPV) GenoArray test kit (HybriBio Ltd) and Thinprep cytologic test (TCT, Hologic, USA) were used to perform HPV genotyping and cytology. All colposcopic images were collected from the standard-of-care colposcope (Leisegang 3ML LED) and evaluated based on the 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) Colposcopy Standards. The linear by linear association, Pearson χ2 test, χ2 test, Kappa test, McNemar test and risk test were used to perform statistical analyses. RESULTS: The consistency between colposcopy and biopsy pathology was 59.35% with the moderate strength of kappa coefficient of 0.464. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy and cytology for HSIL+ were 56.29%, 93.82%, 77.47%, 85.04% and 37.13%, 98.49%, 90.29%, 80.58%, respectively. The colposcopic features of HSIL+ were as follows: (1) thick or bulgy acetowhite epithelium with sharp border; (2) completely nonstained of Lugol's iodine; (3) type III/IV/V of gland openings; (4) punctation or atypical vessels. CONCLUSION: The data and findings herein provide the resource for evaluating the diagnostic value of colposcopy, and suggested that the accuracy of colposcopy is required to be further improved.

The value of microendoscopy in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma.

PURPOSE: Cervical cancer is still one of the main causes of death in females. Conventional diagnostic tools such as colposcopy are still unsatisfactory, so accurate diagnostic tools for cervical diseases are needed. Therefore, the purpose of this study was to perform a clinical study to evaluate the value of microendoscopic imaging systems in the diagnosis of cervical precancerous lesions and cervical microinvasive carcinoma (MIC). METHODS: Totally 106 patients ranging in age from 23 to 67 years were recruited. All patients had abnormal thin-layer cytology (TCT) results (≥ low-grade squamous intraepithelial lesions) and high-risk human papillomavirus (HPV) positivity. Each patient was first subjected to ordinary colposcopy, followed by microendoscopy and biopsy. All results of the colposcopy and microendoscopy images were compared to the histopathological diagnosis. RESULTS: Characteristics of pathological blood vessels were easily distinguished by microendoscopy compared with ordinary colposcopy. The diagnostic agreement rate of microendoscopy with the pathological diagnosis was higher (95.3%) than that of ordinary colposcopy (37.7%) (weighted kappa = 0.863, P < .01). When diagnosing HSIL and more advanced disease, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the microendoscopic diagnosis were significantly higher than those of ordinary colposcopy (97.6 and 38.1%), (95.5 and 63.6%), (98.8 and 80.0%), (91.3 and 21.2%) and (97.7 and 43.4%), respectively. CONCLUSION: This study shows that microendoscopy has important value in the diagnosis of cervical lesions which can provide real-time diagnosis in vivo without staining, particularly for lesions that are not sensitive to acetic acid staining.

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women.

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high-grade squamous intraepithelial lesion (HSIL) group compared to the T," a potential binding site for TATA-binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1-3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 -related cervical lesions/cancer.

Phylogeny and polymorphism in the E6 and E7 of human papillomavirus: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44) in women from Shanghai.

BACKGROUND: Persistent infection with human papillomaviruses (HPVs) has been associated with cervical intraepithelial neoplasia (CIN) and cervical cancer. However, why only a fraction of HPV cases progress to cancer is still unclear. METHODS: We focused on the heterogeneity, classification, evolution and dispersal of variants for 14 common HPV types in 262 HPV-positive patients with cervical lesions. The E6 and E7 genes of HPV were sequenced and compared with the HPV reference for sequence analysis. Phylogenetic trees were constructed using the neighbour-joining tree method with MEGA 7.0. RESULTS: In this study, 233 E6 and 212 E7 sequences were successfully amplified by PCR, and these sequences were divided into 5 species groups: alpha-9 (HPV16, 31, 33, 52, 58), alpha-5 (HPV51), alpha-6 (HPV53, 66), alpha-7 (HPV18, 39, 59, 68) and alpha-10 (HPV6, 44). The incidence of high-grade squamous intraepithelial lesion (HSIL) in patients infected with alpha-9 HPV was significantly increased compared with other groups (P < 0.0001), especially HPV16 (P < 0.0001). Strikingly, E7 had significantly fewer nonsynonymous variants in the HSIL compared to