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IntroductionCoal represents a significant natural resource in our world, and its quality and commercial value is primarily determined by its heating capacity. Numerous scientists worldwide have attempted to explore the impact of various environmental factors on coal rank, yet their conclusions are often inconsistent.MethodsIn this study, the Illumina MiSeq sequencing approach was used to analyze the bacterial community from a low-rank coal mine as well as a high-rank mine. Moreover, we investigated the relationship between the physical and chemical properties of the coal and the bacterial composition.ResultsOverall, we found that the high-rank coal exhibited higher heating value but higher total sulfur and lead levels. Considering the community of bacteria, the abundances of Phascolarctobacterium and Anaerostipes were highly elevated in the high-rank coal group. Most interestingly, the Anaerostipes abundance was correlated with coal quality positively. Additionally, the co-occurrence network of the bacterial community in the high-rank coal group showed much higher complexity. The bacterial functional potential predictions indicated elevated levels of phosphoenolpyruvate carboxykinase ATP, succinate dehydrogenase fumarate reductase flavoprotein subunit, and methylenetetrahydrofolate dehydrogenase NADP methenyltetrahydrofolate cyclohydrolase pathways.ConclusionThis study revealed that high-rank coal had more complicated co-occurrence network and elevated Anaerostipes abundance, which may suggest a potential biological pathway that can be explored to enhance coal quality.

Background: OA (osteoarthritis) is a common joint disease characterized by damage to the articular cartilage and affects the entire joint tissue, with its main manifestations being joint pain, stiffness, and limited movement.Currently,we know that OA is a complex process composed of inflammatory and metabolic factors.It is reported that the occurrence and development of OA is related to the change of tryptophan metabolism.Therefore, the study of tryptophan metabolism and OA related genes is hopeful to find a new therapeutic target for OA. Methods: Differentially expressed genes (DEGs) in GSE55235 were gained via differential expression analysis (OA samples vs normal samples). The tryptophan metabolic related DEGs (TMR-DEGs) were obtained by overlapping tryptophan metabolism related genes (TMRGs) and DEGs. Further, biomarkers were screening via Least absolute shrinkage and selection operator (LASSO), naive bayes (NB) and supportvector machine-recursive feature elimination (SVM-RFE) algorithm to establish a diagnostic model. Afterward, Gene Set Enrichment Analysis (GSEA) and drug prediction were performed based on diagnostic biomarkers by multiple software and databases. Eventually, expression level of biomarker public databases was verified using real-time quantitative polymerase chain reaction (RT-qPCR). Results: Three tryptophan metabolism related biomarkers (TDO2, AOX1 and SLC3A2) were identified in OA. GSEA analysis demonstrated that biomarkers were associated with the function of ‘FoxO signaling pathway’, ‘spliceosome’ and ‘ribosome’. There were seven drugs with therapeutic potential on TDO2 and AOX1. Ultimately, compared with normal group, expression of AOX1 and SLC3A2 in OA group remarkable lower. Conclusion: Overall, three tryptophan metabolic related diagnostic biomarkers that associated with OA were obtained, which provided a original direction for the diagnosis and treatment of OA.

Abstract Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of “fear and worry about choriocarcinoma recurrence”. We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration N/A.

Abstract Objective To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. Methods Patients with BOTs younger than 20 years who underwent FSS were included in this study. Results A total of 34 patients were included, with a median patient age of 17 (range, 3–19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8–40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10–148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. Conclusions Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Objectives Constitutive activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway is central to the pathogenesis of myeloproliferative neoplasms (MPNs). Long noncoding RNAs (lncRNAs) regulate diverse biological processes. However, the role of lncRNAs in MPN pathogenesis is not well studied.Methods The expression of lnc-AC004893 in MPN patients was measured by quantitative real-time PCR (qRT-PCR). Gene-specific short hairpin RNAs (shRNAs) were designed to inhibit the expression of lnc-AC004893, and western blot was performed to explore the role of lnc-AC004893 via regulating the JAK2/STAT5 signaling pathway. Furthermore, co-IP was performed to determine the binding ability of lnc-AC004893 and STAT5 protein. Finally, the BaF3-JAK2V617F-transplanted mouse model was used to assess the biological role of lnc-ac004893 in vivo.Results We report that lnc-AC004893, a poorly conserved pseudogene-209, is substantially upregulated in MPN cells compared with normal controls (NCs). Knockdown of lnc-AC004893 by specific shRNAs suppressed cell proliferation and decreased colony formation. Furthermore, the knockdown of lnc-AC004893 reduced the expression of p-STAT5 but not total STAT5 in HEL and murine IL-3-dependent Ba/F3 cells, which present constitutive and inducible activation of JAK2/STAT5 signaling. In addition, inhibition of murine lnc-ac004893 attenuated BaF3-JAK2V617F-transplanted phenotypes and extended the overall survival. Mechanistically, knockdown of lnc-AC004893 enhanced the binding ability of STAT5 and protein tyrosine phosphatase SHP1. Furthermore, knockdown of lnc-AC004893 decreased STAT5-lnc-AC004893 interaction but not SHP1-lnc-AC004893 interaction.Conclusion Lnc-AC004893 regulates STAT5 phosphorylation by affecting the interaction of STAT5 and SHP1. Lnc-AC004893 might be a potential therapeutic target for MPN patients.

ABSTRACTMesenchymal stem cells (MSCs) with multipotential differentiation ability are main cell source for cartilage tissue engineering, but its application is restricted by the difficulty in regulating committed chondrogenic differentiation. Study revealed that certain substrate topographic structure can enhance the chondrogenic differentiation of MSCs. This study prepared silk fibroin (SF) films with gradient microscopic surface patterns based on P280-P7000 type specification sandpapers, and investigated the adhesion, proliferation and chondrogenic differentiation of human adipose-derived stem cells (hADSCs) on the SF films. The results showed that the SF films surface had convex dots with diameter of 3–50 μm, and hADSCs could adhere and proliferate well on the film. Transcriptomics analysis indicated that hADSCs tend to differentiate differently on the SF films, among which hADSCs on P1000 SF films had higher expression of chondrogenic markers Sox-9 and Col-II, with activated yes associated protein (YAP) and restricted F-actin. In vitro co-culture of human OA knee cartilage with hADSCs seeded SF films found satisfactory cartilage protection effect in P1000 group. Overall, this study preliminarily revealed the microscopic surface pattern of SF films may induce chondrogenic differentiation of hADSCs through extracellular matrix mediated Hippo/Yap pathway, and provided a new strategy for cartilage repair.

Background: This research aimed to create a predictive model and an innovative risk classification system for patients with gallbladder cancer who undergo radical surgery. Methods: A cohort of 1387 patients diagnosed with gallbladder cancer was selected from the SEER database. The researchers devised a prognostic tool known as a nomogram, which was subjected to assessment and fine-tuning using various statistical measures such as the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve, decision curve analysis (DCA), and risk stratification were included in the catalog of comparisons. An external validation set comprising 93 patients from Nanchong Central Hospital was gathered for evaluation purposes. Results: The nomogram effectively incorporated seven variables and demonstrated satisfactory discriminatory ability, as evidenced by the C-index (training cohort: 0.737, validation cohort: 0.730) and time-dependent AUC (>0.7). Additionally, calibration plots confirmed the excellent alignment between the nomogram and actual observations. Our investigation unveiled NRI scores of 0.79, 0.81, and 0.81 in the training group, while the validation group exhibited NRI values of 0.82, 0.77, and 0.78. Additionally, when evaluating CSS at three-, six-, and nine-year intervals using DCA curves, our established nomograms demonstrated significantly improved performance compared to the old model (P

Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes. We performed enrichment analysis, carried out experimental validation, constructed machine learning models, and docked drug molecules. Results: After least absolute shrinkage and selection operator (LASSO) algorithm screening, 4 hub genes (RIPK3, CYBB, HSP90AB1, and TRAF5) with diagnostic characteristics were obtained. Following the comparison of multiple models, the Bayesian model with an average area under curve (AUC) value of 0.944 was finally selected. We found that nimesulide exhibited strong binding affinity to CYBB and HSP90AB1, and experimentally verified that nimesulide reduced the expression of RIPK3 and CYBB, suggesting its potential as an inhibitor of chondrocyte necroptosis. Furthermore, scRNA-seq results showed that necroptosis in OA was significantly upregulated on regulatory chondrocytes (RegC) compared to other chondrocyte subtypes. Conclusions: The results indicate that nimesulide might be used to treat OA by inhibiting chondrocyte necroptosis through down-regulation of RIK3 and CYBB genes. This study reveals the role of chondrocyte necroptosis in OA, and suggests a potential therapeutic strategy by regulating necroptosis with nimesulide.

Abstract Background Ferroptosis is a new form of nonapoptotic and iron-dependent type of cell death. Glutathione peroxidase-4 (GPX4) plays an essential role in anti-ferroptosis by reducing lipid peroxidation. Although acute myeloid leukemia (AML) cells, especially relapsed and refractory (R/R)-AML, present high GPX4 levels and enzyme activities, pharmacological inhibition of GPX4 alone has limited application in AML. Thus, whether inhibition of GPX4 combined with other therapeutic reagents has effective application in AML is largely unknown. Methods Lipid reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) assays were used to assess ferroptosis in AML cells treated with the hypomethylating agent (HMA) decitabine (DAC), ferroptosis-inducer (FIN) RAS-selective lethal 3 (RSL3), or their combination. Combination index (CI) analysis was used to assess the synergistic activity of DAC + RSL3 against AML cells. Finally, we evaluated the synergistic activity of DAC + RSL3 in murine AML and a human R/R-AML-xenografted NSG model in vivo. Results We first assessed GPX4 expression and found that GPX4 levels were higher in AML cells, especially those with MLL rearrangements, than in NCs. Knockdown of GPX4 by shRNA and indirect inhibition of GPX4 enzyme activity by RSL3 robustly induced ferroptosis in AML cells. To reduce the dose of RSL3 and avoid side effects, low doses of DAC (0.5 µM) and RSL3 (0.05 µM) synergistically facilitate ferroptosis by inhibiting the AMP-activated protein kinase (AMPK)-SLC7A11-GPX4 axis. Knockdown of AMPK by shRNA enhanced ferroptosis, and overexpression of SLC7A11 and GPX4 rescued DAC + RSL3-induced anti-leukemogenesis. Mechanistically, DAC increased the expression of MAGEA6 by reducing MAGEA6 promoter hypermethylation. Overexpression of MAGEA6 induced the degradation of AMPK, suggesting that DAC inhibits the AMPK-SLC7A11-GPX4 axis by increasing MAGEA6 expression. In addition, DAC + RSL3 synergistically reduced leukemic burden and extended overall survival compared with either DAC or RSL3 treatment in the MLL-AF9-transformed murine model. Finally, DAC + RSL3 synergistically reduced viability in untreated and R/R-AML cells and extended overall survival in two R/R-AML-xenografted NSG mouse models. Conclusions Our study first identify vulnerability to ferroptosis by regulating MAGEA6-AMPK-SLC7A11-GPX4 signaling pathway. Combined treatment with HMAs and FINs provides a potential therapeutic choice for AML patients, especially for R/R-AML.

Abstract Background A surge of more than 80 million Omicron variant infected cases was reported in China less than a month after the "zero COVID" strategy ended on December 7, 2022. In this circumstance, whether people living with HIV (PLWH) in China experience a similar risk is not clear. Methods A cross-sectional study was conducted in the Wuchang District of Wuhan between December 20, 2022, and January 18, 2023 through a self-administered online survey. PLWH and HIV-negative people aged ≥ 18 years old who volunteered for this survey were eligible. The prevalence of Omicron variant infection between PLWH and HIV-negative people was compared, and the factors associated with the Omicron variant infection among PLWH and HIV-negative people were further evaluated, respectively. Results In total, 890 PLWH and 1,364 HIV-negative adults from Wuchang District were enrolled. Among these participants, 690 PLWH (77.5%) and 1163 HIV-negative people (85.3%) reported SARS-CoV-2 infection. Gender, chronic disease conditions, and COVID-19 vaccination status significantly differed between the two groups. After adjusting gender, age, comorbidities, and COVID-19 vaccination status, the risk of SARS-CoV-2 infection among PLWH was significantly lower than among HIV-negative people (aOR 0.56, 95%CI 0.42–0.76). Multivariable logistic regression analysis showed that PLWH with older age and detectable HIV-viral load (HIV-VL) had decreased risk of SARS-CoV-2 infection (aOR 0.98, 95%CI 0.96–0.99; aOR 0.59, 95%CI 0.36–0.97). Compared with PLWH receiving one/two doses of COVID-19 vaccines, no significant differences in the risk of SARS-CoV-2 infection were observed among PLWH receiving three doses of inactivated vaccines and four doses of vaccines (three doses of inactivated vaccines plus one dose of inhaled recombinant adenovirus type 5 (AD5)-vectored vaccine). Among HIV-negative people, those receiving four doses of COVID-19 vaccines had a lower risk of SARS-CoV-2 infection than those receiving one/two doses (aOR 0.14, 95%CI 0.08–0.25). Conclusions Our study proves that PLWH have a lower risk of Omicron variant infection than HIV-negative people. However, even PLWH with younger age and virological suppression should strengthen the prevention against SARS-CoV-2 infection. Three doses of inactivated vaccines plus one dose of inhaled recombinant AD5-vectored COVID-19 vaccine may provide better protection for HIV-negative people.

To date, few studies have investigated whether the RNA-editing enzymes adenosine deaminases acting on RNA (ADARs) influence RNA functioning in lung adenocarcinoma (LUAD). To investigate the role of ADAR in lung cancer, we leveraged the advantages of The Cancer Genome Atlas (TCGA) database, from which we obtained transcriptome data and clinical information from 539 patients with LUAD. First, we compared ARAR expression levels in LUAD tissues with those in normal lung tissues using paired and unpaired analyses. Next, we evaluated the influence of ADARs on multiple prognostic indicators, including overall survival at 1, 3 and 5 years, as well as disease-specific survival and progression-free interval, in patients with LUAD. We also used Kaplan-Meier survival curves to estimate overall survival and Cox regression analysis to assess covariates associated with prognosis. A nomogram was constructed to validate the impact of the ADARs and clinicopathological factors on patient survival probabilities. The volcano plot and heat map revealed the differentially expressed genes associated with ADARs in LUAD. Finally, we examined ADAR expression versus immune cell infiltration in LUAD using Spearman's analysis. Using the Gene Expression Profiling Interactive Analysis (GEPIA2) database, we identified the top 100 genes most significantly correlated with ADAR expression, constructed a protein-protein interaction network and performed a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis on these genes. Our results demonstrate that ADARs are overexpressed in LUAD and correlated with poor patient prognosis. ADARs markedly increase the infiltration of T central memory, T helper 2 and T helper cells, while reducing the infiltration of immature dendritic, dendritic and mast cells. Most immune response markers, including T cells, tumor-associated macrophages, T cell exhaustion, mast cells, macrophages, monocytes and dendritic cells, are closely correlated with ADAR expression in LUAD.

Background: Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE).Methods: We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The in vivo therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes.Results: Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the in vivo OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments.Discussion: The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.

BackgroundThis study aimed to develop a prognostic model for patients with advanced ductal adenocarcinoma aged ≥50 years.MethodsPatient information was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to screen the model variables. Cases from Nanchang Central Hospital were collected for external validation. The new nomogram and the American Joint Committee on Cancer (AJCC) criteria were evaluated using integrated discrimination improvement (IDI) and net reclassification index (NRI) indicators. Survival curves presented the prognosis of the new classification system and AJCC criteria.ResultsIn total, 17,621 eligible patients were included. Lasso Cox regression selected 4 variables including age, chemotherapy, radiotherapy and AJCC stage. The C-index of the training cohort was 0.721. The C-index value of the validation cohort was 0.729. The AUCs for the training cohorts at 1, 2, and 3 years were 0.749, 0.729, and 0.715, respectively. The calibration curves showed that the predicted and actual probabilities at 1, 2, and 3 years matched. External validation confirmed the model’s outstanding predictive power. Decision curve analysis indicated that the clinical benefit of the nomogram was higher than that of the AJCC staging system. The model evaluation indices preceded the AJCC staging with NRI (1-year: 0.88, 2-year: 0.94, 3-year: 0.72) and IDI (1-year: 0.24, 2-year: 0.23, 3-year: 0.22). The Kaplan–Meier curves implied that the new classification system was more capable of distinguishing between patients at different risks.ConclusionsThis study established a prognostic nomogram and risk classification system for advanced pancreatic cancer in patients aged ≥50 years to provide a practical tool for the clinical management of patients with pancreatic ductal adenocarcinoma.

Abstract Objective To describe myeloid sarcoma (MS) that mimic gynecological tumors and provide guidelines for improving the diagnosis and treatment of patients. Methods This case series study retrospectively analyzed the clinicopathological characteristics and oncological outcomes of female patients who were histologically diagnosed with MS after initially presenting with reproductive-system tumors at the Peking Union Medical College Hospital between January 2000 and March 2022. Results There were eight cases in which MS mimicked cervical cancer, ovarian cancer, or hysteromyoma. Six patients had isolated MS, and the other two had acute myeloid leukemia (AML)-M2. The average age was 39.00 ± 14.26. They each sought advice from a gynecological oncologist at the initial visit, complaining of irregular bleeding (3/8), low abdominal pain (3/8), dysmenorrhea (1/8), or an accidentally found mass (1/8). CT/MRI exams revealed that the average tumor size reached 5.65 ± 2.35 cm, with 50% of the tumors being larger than 8 cm. The final diagnoses were confirmed by biopsy (2/8) or postoperative pathology (6/8); the most frequent positive immunohistochemical markers were Ki-67 (60–90%), MPO (100%), LCA (62.5%), CD43 (62.5%), CD117 (62.5%), CD99 (50%), vimentin (37.5%), and lysozyme (25%). MLL/AF9 gene fusions and CEBPA, JAK2, NRAS, and FLT3-TKD mutations were found in the patients. Six (75%) of the patients showed a complete response after upfront treatment using chemotherapy + surgery and experienced no recurrence during follow-up. The overall survival (OS) rate was 72.9%, and the 5-year OS rate was 72.9% (95%CI: 0.4056–1.000). The median OS was 26 months (range: 3–82). Conclusion For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.

The spatial distribution of soil moisture is a critical determinant for the success of vegetation restoration initiatives in semi-arid and arid regions. The Qilian Mountains, situated within a semi-arid zone in China, have been subject to significant water-induced soil erosion, which has led to extensive restoration activities, predominantly utilizing the species P. crassifolia. However, the interconnections between soil moisture and various land cover types within this region remain unclear, presenting challenges to effective woodland rehabilitation. This study examines the surface soil moisture dynamics in afforested areas with varying ages of plantation to determine the influence of tree planting on the moisture content of the upper soil layer. It investigates the characteristics and temporal patterns of surface soil moisture as the age of the plantation increases. The findings indicate that: (1) soil moisture levels follow a descending sequence from natural forest, through shrubland and grassland, to planted forest and mixed forest, with statistically significant differences observed between natural and mixed forests (p < 0.05); (2) young afforested areas (less than 50 years old) have lower soil moisture levels compared to natural forests, shrublands, or grasslands, and the ecohydrological impacts of afforestation become apparent with a temporal delay; and (3) the analysis using Generalized Additive Mixed Models (GAMM) and the application of Kriging interpolation to determine the spatial distribution of soil moisture reveals that in semi-arid and arid regions, several factors have a pronounced a non-linear relationship with the moisture content of the surface soil. These factors include the duration of afforestation, the position on the lower slope, the presence of shade on the slope, and the scale at which the study is conducted. Therefore, a comprehensive understanding of the dynamics of soil water content is essential to prevent the potential failure of artificially established forests due to inadequate soil moisture in their later stages.

Summary: Objective: To compare the difference in efficacy and accuracy during total knee arthroplasty (TKA) among robotic-arm system, patient-specific instrumentation (PSI) and conventional TKA (COTKA). Methods: Retrospective analysis of 90 advanced knee osteoarthritis (OA) patients in our hospital between June 2019 and December 2020 was conducted. Patients were divided into robotic arm-assisted (RA)TKA (group A), PSITKA (group B) and COTKA (group C), 30 cases in each group. The operation time, intraoperative bleeding, and length of hospital stay were counted. Imaging data of hip–knee–ankle angle (HKA), posterior condylar angle (PCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and sagittal tibial component angle (sTCA) were statistically analyzed. The postoperative recovery of the patients was evaluated by Knee Society Score (KSS) and the Western Ontario Mac Master University Index Score (WOMAC). Results: Group A had the least intraoperative bleeding. For operation time, group A was the longest compared with group B and group C (P

Reinforcement learning (RL) can obtain the supervisory controller for discrete-event systems modeled by finite automata and temporal logic. The published methods often have two limitations. First, a large number of training data are required to learn the RL controller. Second, the RL algorithms do not consider uncontrollable events, which are essential for supervisory control theory (SCT). To address the limitations, we first apply SCT to find the supervisors for the specifications modeled by automata. These supervisors remove illegal training data violating these specifications and hence reduce the exploration space of the RL algorithm. For the remaining specifications modeled by temporal logic, the RL algorithm is applied to search for the optimal control decision within the confined exploration space. Uncontrollable events are considered by the RL algorithm as uncertainties in the plant model. The proposed method can obtain a nonblocking supervisor for all specifications with less learning time than the published methods.

An ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of 9 mycotoxins in fruit. Sample extraction, purification conditions and instrument conditions were optimized. The samples were ultrasonic extracted with 10 mmol/L citric acid acetonitrile solution and salted out by adding NaCl. After centrifugation, the supernatant was cleaned up by C18 sorbent and separated on an ACQUITY UPLC BEH C18 column. The analytes were detected in the multiple reaction monitoring mode after being ionized by an electrospray positive ion. Quantitative analysis was performed by the external standard method using matrix-matched calibration curves. The results showed that all the 9 mycotoxins were well separated in 5 min. The coefficients of determination (R2) were greater than 0.999, suggesting good linearity of the method in the mass concentration range. The method limits of detection (3S/N) and limits of quantification (10S/N) were 0.004~1.676 μg/kg and 0.014~5.587 μg/kg, respectively. The recovery experiments were performed with peach and cherry samples at three spiked levels (low, medium and high) were 84.5%~113.2% with the relative standard deviations were 0.7%~4.0% (n=6). This method was used to analyze the contamination status of 9 mycotoxins in fruit samples (strawberry, cherry, grape, apple and pear). The results showed that beauvericin, patulin and Altenuene toxins were found in cherry and grape samples, and their contents were ranged from ND (not detected) ~12.47 µg/kg. The method is proved to be stable, accurate, sensitive and rapid, and can meet the requirements for the analysis of 9 mycotoxins residues in a variety of fruit samples.

Summary: Background: Synergistic antitumor effects of immunotherapy and chemotherapy have been demonstrated in several solid tumors. However, this combination strategy has not been addressed in gestational trophoblastic neoplasia (GTN) cases. We therefore compared the safety and therapeutic effect of anti-programmed cell death 1 (PD-1) therapy combined with chemotherapy versus anti-PD-1 monotherapy among high-risk chemorefractory or relapsed GTN patients. Methods: This retrospective cohort study was conducted at three teaching hospitals in China. Chemorefractory or relapsed GTN cases receiving anti-PD-1 therapy combined with chemotherapy or anti-PD-1 monotherapy were selected from each center between August 2018 and March 2022. Study endpoints included objective response rate (ORR), treatment duration, overall survival (OS) and progression-free survival (PFS). The nature, prevalence and severity of treatment-related adverse events (TRAEs) were evaluated. Findings: This work enrolled 66 cases. Thirty-five and 31 patients received anti-PD-1 therapy alone and combined with chemotherapy, respectively. The combined treatment dramatically increased the objective response rate from 62.9% (22/35) to 96.8% (30/31) (p

Abstract Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) and antitumor immunity synchronously urgently needed. Here, the authors developed a nanoscale metal–organic framework (MOF, named TZM) by co‐doping high‐atomic elements Ta and Zr as metal nodes and porphyrinic molecules (tetrakis(4‐carboxyphenyl)porphyrin (TCPP)) as a photosensitizing ligand. Given the 3D arrays of ultra‐small heavy metals, porous TZM serves as an efficient attenuator absorbing X‐ray energy and sensitizing hydroxyl radical generation for RT. Ta–Zr co‐doping narrowed the highest occupied molecular orbital‐lowest unoccupied molecular orbital (HOMO–LUMO) energy gap and exhibited close energy levels between the singlet and triplet photoexcited states, facilitating TZM transfer energy to the photosensitizer TCPP to sensitize singlet oxygen (1O2) generation for radiodynamic therapy (RDT). The sensitized RT–RDT effects of TZM elicit a robust antitumor immune response by inducing immunogenic cell death, promoting dendritic cell maturation, and upregulating programmed cell death protein 1 (PD‐L1) expression via the cGAS–STING pathway. Furthermore, a combination of TZM, X‐ray, and anti‐PD‐L1 treatments amplify antitumor immunotherapy and efficiently arrest osteosarcoma growth and metastasis. These results indicate that TZM is a promising radiosensitizer for the synergistic RT and immunotherapy of metastatic osteosarcoma.

Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin β1, ERK1/2 and vinculin (VCL) in vitro. In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin β1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo. In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin β1/ERK/VCL pathway. Our findings may provide new insights in MSCs intra-articular injection for OA treatment.

Objectives: To evaluate the expression of emerging immune targets in the tumor-infiltrating immunocytes (TIIs) of human gestational trophoblastic neoplasia (GTN) specimens, and to analyze the correlation between the expression patterns and prognosis of GTN patients.Methods: Between January 2008 and December 2017, patients who were diagnosed histologically with GTN were included in this study. The expression densities of LAG-3, TIM-3, GAL-9, PD-1, CD68, CD8, and FOXP3 in the TIIs were assessed independently by two pathologists blinded to clinical outcomes. The expression patterns and correlation with patient outcomes were analyzed to identify prognostic factors.Results: We identified 108 patients with GTN, including 67 with choriocarcinoma, 32 with placental site trophoblastic tumor (PSTT), and 9 with epithelioid trophoblastic tumor (ETT). Almost all GTN patients showed expression of GAL-9, TIM-3, and PD-1 in TIIs (100%, 92.6%, and 90.7%, respectively); LAG-3 was expressed in 77.8% of the samples. The expression densities of CD68 and GAL-9 were significantly higher in choriocarcinoma than that in PSTT and ETT. The TIM-3 expression density in choriocarcinoma was higher than that in PSTT. In addition, the expression density of LAG-3 in the TIIs of choriocarcinoma and PSTT was higher than that in ETT. There was no statistical difference in the expression pattern of PD-1 among different pathological subtypes. The positive expression of LAG-3 in tumor TIIs was a prognostic factor for disease recurrence, and patients with positive expression of LAG-3 in the TIIs had poorer disease-free survival (p = 0.026).Conclusion: Our study evaluated the expression of immune targets PD-1, TIM-3, LAG-3, and GAL-9 in the TIIs of GTN patients and found that they were widely expressed but not associated with patients’ prognoses, excepting the positive expression of LAG-3 was a prognostic factor for disease recurrence.

Abstract The wettability and adhesion of biological surfaces often depend on their periodically arranged hybrid micro–nano array structures. Various fabrication processes are designed to mimic biomimetic micro–nano array surfaces. This review summarizes the types of micro–nano array structures and analyzes fabrication methods based on top‐down and bottom‐up construction, including templating, etching, self‐assembly, and electrospinning/electrospraying. This review focuses on the shape reconfiguration of surface micro–nano array structures under physical stimuli, as well as the changes in material surface properties during the reconfiguration process. In addition, the applications of biomimetic micro–nano array composite surfaces in the fields of droplet transport, adhesion properties, sensors, and soft robotics are also discussed, and the current challenges and prospects in this field are identified.

ObjectiveTo compare the oncological outcomes of radical surgery and radical radiotherapy in elderly (over 65 years) patients with early-stage cervical cancer (IB-IIA).MethodsElderly patients with stage IB-IIA cervical cancer treated at Peking Union Medical College Hospital from January 2000 to December 2020 were retrospectively reviewed. All patients were divided into the radiotherapy group (RT group) and the operation group (OP group) according to their primary intervention. Propensity score matching (PSM) analysis was performed to balance the biases. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and adverse effects.ResultsA total of 116 patients were eligible for the study (47 in the RT group, and 69 in the OP group), and after PSM, 82 patients were suitable for further analysis (37 in the RT group, and 45 in the OP group). In the real-world setting, it was found that compared with radiotherapy, operation was more frequently selected for elderly cervical cancer patients with adenocarcinoma (P < 0.001) and IB1 stage cancer (P < 0.001). The 5-year PFS rates between the RT and OP groups were not significant (82.3% vs. 73.6%, P = 0.659), and the 5-year OS rate of the OP group was significantly better than that in the RT group (100% vs. 76.3%, P = 0.039), especially in patients with squamous cell carcinoma (P = 0.029) and tumor size of 2~4 cm with G2 differentiation (P = 0.046). There was no significant difference in PFS between the two groups (P = 0.659). In the multivariate analysis, compared with operation, radical radiotherapy was an independent risk factor of OS (hazard ratio = 4.970, 95% CI, 1.023~24.140, P = 0.047). No difference was observed in adverse effects between the RT and OP groups (P = 0.154) and in ≥grade 3 adverse effects (P = 0.852).ConclusionThe study found that surgery was more frequently selected for elderly cervical cancer patients with adenocarcinoma and IB1 stage cancer in the real-world setting. After PSM to balance the biases, it showed that compared with radiotherapy, surgery could improve the OS of elderly early-stage cervical cancer patients and was an independent protective factor of OS in elderly early-stage cervical cancer patients.

BackgroundGynecological cancer is one of the most common cancers in women. The quality of life (QoL) or psychological impact has emerged as an outcome indicator in many clinical trials of gynecological cancer and gained much concern in the clinical setting at the start of the 21st century. Our paper conducted a bibliometric analysis of QoL or psychological impact on gynecological cancer patients to show the status and hotspots.MethodsRelated publications from 2000 to 2022 were included by screening from the Web of Science Core Collection (WOSCC) on 26 June 2022. The bibliometrics was analyzed and visualized by bibliometrix R-package, VOSviewer, and CiteSpace V.ResultsA total of 6,479 publications were included in our study. The publications in this field were increased annually. The United States (n = 2,075) was the country with the most published papers. Sydney University (n = 167) was the most productive affiliation. Gynecologic Oncology and Journal of Clinical Oncology were the most relevant and most cited sources, respectively. The article written by Bray F et al. has the highest citation. Kim J and Aaronson NK ranked first in most productive author and most co-cited author, respectively. The keywords “mortality”, “fertility preservation”, and “palliative care” have bursts till 2022, which represented the frontiers of this field.ConclusionOur study provides an overall analysis of QoL or psychological impact on gynecological cancer patients, which can serve as a reference in future research.

Recent studies highlight the vital role of oxidative stress and reactive oxygen species (ROS) during progression of osteoarthritis (OA). Attenuating oxidative stress and reducing reactive oxygen species generation in joints represent reasonable strategies for the treatment of osteoarthritis. To address the potential question for clinical translation, and improve the biocompatibility and long-term performance of current antioxidants, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity and first applied to osteoarthritis intervention. Our in vitro results showed that Ta-NH2 NPs were stable with good biocompatibility, and protected viability and hyaline-like phenotype in H2O2-challenged chondrocytes. In addition, the in vivo biodistribution data demonstrated a sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage without organ toxicity and abnormality in hemogram or blood biochemistry indexes. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced osteoarthritis model. This study preliminarily explored the potential of simply modified metal nanoparticles as effective reactive oxygen species scavenging agent for osteoarthritis intervention, and offered a novel strategy to achieve sustained reactive oxygen species suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.

Abstract Objectives To investigate the utility of three-dimensional (3D) amide proton transfer-weighted (APTw) imaging to differentiate mismatch repair deficient (dMMR) and mismatch repair proficient (pMMR) tumors in endometrioid endometrial adenocarcinoma (EEA). Methods Forty-nine patients with EEA underwent T1-weighted imaging, T2-weighted imaging, 3D APTw imaging, and diffusion-weighted imaging at 3 T MRI. Image quality and measurement confidence of APTw images were evaluated on a 5-point Likert scale. APTw and apparent diffusion coefficient (ADC) values were calculated and compared between the dMMR and pMMR groups and among the three EEA histologic grades based on the Federation of Gynecology and Obstetrics (FIGO) grading system criteria. Student’s t-test, analysis of variance with Scheffe post hoc test, and receiver operating characteristic analysis were performed. Statistical significance was set at p

Background: Bone marrow stimulation (BMS) is the most used operative treatment in repairing cartilage defect clinically, but always results in fibrocartilage formation, which is easily worn out and needs second therapy. In this study, we prepared an Etanercept (Ept) embedded silk fibroin/pullulan hydrogel to enhance the therapeutic efficacy of BMS.Methods: Ept was dissolved in silk fibroin (SF)—tyramine substituted carboxymethylated pullulan (PL) solution and enzyme crosslinked to obtain the Ept contained SF/PL hydrogel. The synergistical effect of SF/PL hydrogel and Ept was verified by rabbit osteochondral defect model. The mechanism of Ept in promoting articular cartilage repair was studied on human osteoarthritic chondrocytes (hOACs) and human bone marrow mesenchymal stromal cells (hBMSCs) in vitro, respectively.Results: At 4 and 8 weeks after implanting the hydrogel into the osteochondral defect of rabbit, histological analysis revealed that the regenerated tissue in Ept + group had higher cellular density with better texture, and the newly formed hyaline cartilage tissue was seamlessly integrated with adjacent native tissue in the Ept + group. In cellular experiments, Ept treatment significantly promoted both gene and protein expression of type II collagen in hOACs, while decreased the protein levels of metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs 5 (ADAMTS5); alcian blue staining, type II collagen and aggrecan stainings showed that addition of Ept significantly reversed the chondrogenesis inhibition effect of tumor necrosis factor alpha (TNF-α) on hBMSCs.Conclusion: BMS could be augmented by Ept embedded hydrogel, potentially by regulating the catabolic and anabolic dynamics in adjacent chondrocytes and enhancement of BMSCs chondrogenesis.

Abstract Background Primary cervical gestational trophoblastic neoplasias (GTNs) are extremely rare ectopic GTNs. Such lesions are difficult to diagnose clinically because of their rarity, with abnormal vaginal bleeding of a non-specific cause being the most common symptom. To that end, this retrospective study aimed to identify the clinical characteristics of cervical GTN and to explore diagnostic and therapeutic strategies. Results Thirteen patients diagnosed with primary cervical GTN at the Department of Gynecology, Peking Union Medical College Hospital, Beijing, China, between June 1, 1988 and May 31, 2020 were included in the study. All patients had irregular vaginal bleeding, including six who presented with massive bleeding. Seven patients (53.8%) were initially misdiagnosed with a cervical pregnancy. All patients received chemotherapy; 11 (84.6%) also underwent hysterectomy because of chemoresistant lesions or uncontrolled bleeding. All patients achieved complete remission; however, two women (15.4%) experienced a relapse during the median follow-up period of 35 months. A comprehensive review of English-language literature published between 1980 and 2020 identified 22 case reports encompassing 27 patients. The definitive diagnosis was achieved via pathology in 26 of them (96.3%), and hysterectomy was performed in 21 (77.8%). Conclusions Owing to its rarity and nonspecific symptoms, the diagnosis of primary cervical GTN is challenging and often relies on pathology. The combination of chemotherapy and hysterectomy is the main therapeutic strategy for this disease.

IntroductionDelayed neurocognitive recovery (DNR) is a common post-surgical complication among the elderly. Cognitive frailty (CF) is also an age-related medical syndrome. However, little is known about the association between CF and DNR. Therefore, this study aimed to study whether CF is associated with DNR in elderly patients undergoing elective noncardiac surgery, as well as to explore the potential risk factors for DNR in frail elderly individuals and construct a prediction model.MethodsThis prospective cohort study administered a battery of cognitive and frailty screening instruments for 146 individuals (≥65 years old) scheduled for elective noncardiac surgery. Screening for CF was performed at least one day before surgery, and tests for the presence of DNR were performed seven days after surgery. The association between CF and DNR was investigated. Moreover, the study subjects were randomly divided into a modeling group (70%) and a validation group (30%). Univariate and multivariate logistic regression was performed to analyze the modeling group data and identify the independent risk factors for DNR. The R software was used to construct DNR's nomogram model, verifying the model.ResultsIn total, 138 individuals were eligible. Thirty-three cases were diagnosed with DNR (23.9%). No significant difference in the number of patients with CF was observed between the DNR and non-DNR groups (P > 0.05). Multivariate analysis after adjusting relevant risk factors showed that only the judgment of line orientation (JLOT) test score significantly affected the incidence of DNR. After internal validation of the constructed DNR prediction model, the area under the curve (AUC) of the forecast probability for the modeling population (n = 97) for DNR was 0.801, and the AUC for the validation set (n = 41) was 0.797. The calibration curves of both the modeling and validation groups indicate that the prediction model has good stability.ConclusionCognitive frailty is not an independent risk factor in predicting DNR after noncardiac surgery in frail elderly individuals. The preoperative JLOT score is an independent risk factor for DNR in frail elderly individuals. The prediction model has a good degree of discrimination and calibration, which means that it can individually predict the risk probability of DNR in frail elderly individuals.

PurposeWe designed to construct one 3D VOI-based deep learning radiomics strategy for identifying lymph node metastases (LNM) in pancreatic ductal adenocarcinoma on the basis of multiphasic contrast-enhanced computer tomography and to assist clinical decision-making.MethodsThis retrospective research enrolled 139 PDAC patients undergoing pre-operative arterial phase and venous phase scanning examination between 2015 and 2021. A primary group (training group and validation group) and an independent test group were divided. The DLR strategy included three sections. (1) Residual network three dimensional-18 (Resnet 3D-18) architecture was constructed for deep learning feature extraction. (2) Least absolute shrinkage and selection operator model was used for feature selection. (3) Fully connected network served as the classifier. The DLR strategy was applied for constructing different 3D CNN models using 5-fold cross-validation. Radiomics scores (Rad score) were calculated for distinguishing the statistical difference between negative and positive lymph nodes. A clinical model was constructed by combining significantly different clinical variables using univariate and multivariable logistic regression. The manifestation of two radiologists was detected for comparing with computer-developed models. Receiver operating characteristic curves, the area under the curve, accuracy, precision, recall, and F1 score were used for evaluating model performance.ResultsA total of 45, 49, and 59 deep learning features were selected via LASSO model. No matter in which 3D CNN model, Rad score demonstrated the deep learning features were significantly different between non-LNM and LNM groups. The AP+VP DLR model yielded the best performance in predicting status of lymph node in PDAC with an AUC of 0.995 (95% CI:0.989-1.000) in training group; an AUC of 0.940 (95% CI:0.910-0.971) in validation group; and an AUC of 0.949 (95% CI:0.914-0.984) in test group. The clinical model enrolled the histological grade, CA19-9 level and CT-reported tumor size. The AP+VP DLR model outperformed AP DLR model, VP DLR model, clinical model, and two radiologists.ConclusionsThe AP+VP DLR model based on Resnet 3D-18 demonstrated excellent ability for identifying LNM in PDAC, which could act as a non-invasive and accurate guide for clinical therapeutic strategies. This 3D CNN model combined with 3D tumor segmentation technology is labor-saving, promising, and effective.

Euler deconvolution is a popular technique used for analyzing potential field data because it requires little prior information. However, the reliability of Euler solutions can be impacted by interference from adjacent field sources, or background fields. In this manuscript, we present an effective Euler deconvolution algorithm that accounts for linear background fields. Our algorithm, called improved finite-difference Euler deconvolution, builds upon the finite-difference method and is less susceptible to interference from nearby sources. We use this algorithm to achieve a joint estimation of the coefficients of the source coordinates, the structure index, and the linear background trend. Compared to Euler deconvolution methods based on differential similarity transformations, which also account for linear background fields, our method is easier to understand and implement programmatically and is faster. We tested our method using both 2D and 3D synthetic data, and the results indicate that our algorithm has better computational accuracy than the finite-difference algorithm and is comparable to the Euler deconvolution algorithm based on differential similarity transformations. In addition, our method was shown to be effective when tested on real data.

Mesenchymal stem cells (MSCs) have recently been widely used to treat osteoarthritis (OA). Our prior research shows that tropoelastin (TE) increases MSC activity and protects knee cartilage from OA-related degradation. The underlying mechanism might be that TE regulates the paracrine of MSCs. Exosomes (Exos), the paracrine secretion of MSCs, have been found to protect chondrocytes, reduce inflammation, and preserve the cartilage matrix. In this study, we used Exos derived from TE-pretreated adipose-derived stem cells (ADSCs) (TE-ExoADSCs) as an injection medium, and compared it with Exos derived from unpretreated ADSCs (ExoADSCs). We found that TE-ExoADSCs could effectively enhance the matrix synthesis of chondrocytes in vitro. Moreover, TE pretreatment increased the ability of ADSCs to secrete Exos. In addition, compared with ExoADSCs, TE-ExoADSCs exhibited therapeutic effects in the anterior cruciate ligament transection (ACLT)-induced OA model. Further, we observed that TE altered the microRNA expression in ExoADSCs and identified one differentially upregulated microRNA: miR-451-5p. In conclusion, TE-ExoADSCs helped maintain the chondrocyte phenotype in vitro, and promoted cartilage repair in vivo. These therapeutic effects might be related with the altered expression of miR-451-5p in the ExoADSCs. Thus, the intra-articular delivery of Exos derived from ADSCs with TE pretreatment could be a new approach to treat OA.

Abstract Background Choriocarcinoma is a rare malignant neoplasm, which is classified as either gestational choriocarcinoma or nongestational choriocarcinoma. The purpose of this study was to examine the clinical characteristics of Chinese female nongestational choriocarcinoma patients and discuss our experience in treating this rare disease. Results We conducted a single-center retrospective study on a sample of 37 nongestational choriocarcinoma patients who were diagnosed and treated at Peking Union Medical College Hospital from March 1982 to March 2020. Their demographic, clinical, laboratory, and therapeutic data were collected. Detailed information was available for all 37 individuals in our sample. The primary lesions included 34 in the ovaries, 2 in the pituitary and 1 in the stomach. The median age of onset was 22 years, and the median follow-up period spanned 41 months. The lungs (40.5%) were the most commonly observed metastatic site. All subjects were treated with surgery and multidrug chemotherapies, and a median of 4.0 courses was required to achieve complete remission. The overall complete response rate, relapse rate, and 3-year and 5-year survival rates were 81.1%, 16.7%, 80.0%, and 75.5%, respectively. Conclusions Nongestational choriocarcinoma can be managed well using surgery and multidrug chemotherapies, but the overall outcome of nongestational choriocarcinoma is still worse than that of gestational choriocarcinoma. Mixed nongestational choriocarcinoma seems to have similar therapeutic outcomes as pure tumors.

Abstract Background Osteoarthritis (OA), the most common joint disorder, is characterized by a progressive degradation of articular cartilage. Increasing evidence suggests that OA is closely associated with cartilage pathologies including chondrocyte hypertrophy and fibrosis. Methods In this study, we showed that asiatic acid (AA) treatment reduced chondrocyte hypertrophy and fibrosis. First, the cytotoxicity of AA (0, 5, 10, and 20 μM) to chondrocytes was evaluated, and 5 μM was selected for subsequent experiments. Then, we detected the gene and protein level of chondrocyte hypertrophic markers including type X collagen (COL-X), matrix metalloproteinase-13 (MMP-13), alkaline phosphatase (ALP), and runt-related transcription factor 2 (Runx2); chondrocyte fibrosis markers including type I collagen (COL-Ι) and alpha-smooth muscle actin (α-SMA); and chondrogenic markers including SRY-related HMG box 9 (SOX9), type II collagen (COL-II), and aggrecan (ACAN). Further, we tested the mechanism of AA on inhibiting chondrocyte hypertrophy and fibrosis. Finally, we verified the results in an anterior cruciate ligament transection (ACLT) rat OA model. Results We found that AA treatment inhibited the hypertrophic and fibrotic phenotype of chondrocytes, without affecting the chondrogenic phenotype. Moreover, we found that AA treatment activated AMP-activated protein kinase (AMPK) and inhibited phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) signaling pathway in vitro. The results in an ACLT rat OA model also indicated that AA significantly attenuated chondrocyte hypertrophy and fibrosis. Conclusion AA treatment could reduce hypertrophic and fibrotic differentiation and maintain the chondrogenic phenotype of articular chondrocytes by targeting the AMPK/PI3K/AKT signaling pathway. Our study suggested that AA might be a prospective drug component that targets hypertrophic and fibrotic chondrocytes for OA treatment.

Abstract Objective We investigated the clinical characteristics, treatments, and survival of patients with gestational trophoblastic neoplasia (GTN) who experienced recurrence. Factors predictive of recurrence were also investigated. Methods Patients with GTN who recurred after completing chemotherapy at Peking Union Medical College Hospital Trophoblastic Disease Center were identified between January 2004 and December 2017. Logistic regression analysis was used to identify factors predictive of GTN recurrence. Results A total of 1827 patients with GTN achieved complete remission (CR) at our center, of whom 118 (6.5%) experienced recurrence during follow‐up. The recurrence rates for patients initially treated at our center and those referred to us were 2.7% and 14.6%, respectively. The majority of recurrent patients received floxuridine‐based multiagent chemotherapy (n = 64). Patients who underwent surgery achieved a significantly higher CR rate than those who did not (88.6% vs 61.1%, P = .001). Although 94.1% of recurrent patients reachieved CR, 33.3% of them recurred for a second time. The 5‐year survival rate of the entire cohort was 80.4%. An interval between antecedent pregnancy and chemotherapy >12 months (OR: 6.600, 95% CI [3.217‐13.540], P 14 weeks (OR: 2.226, 95% CI [1.080‐4.588], P = .030) were predictors of recurrence. Conclusions Patients with recurrent GTN are prone to recurring for a second time. Surgery plays a beneficial role in the management of recurrent GTN. An interval between antecedent pregnancy and chemotherapy >12 months, and an interval from first chemotherapy to achieving β‐hCG normalization >14 weeks were predictors of recurrence.

Background Understanding the mechanism of chondrocytes degeneration could provide a new potential therapeutic idea for rheumatoid arthritis (RA) treatment. MicroRNA-27b-3p (miR-27b-3p) has been shown to regulate a variety of cell behaviors in various cell types. However, the role of miR-27b-3p in RA remains unknown.Materials and methods Expression of miR-27b-3p and HIPK2 in cartilage tissues and chondrocytes was characterized using qRT-PCR and Western blot. MiR-27b-3p was overexpressed or suppressed in chondrocytes to observe the potential role of miR-27b-3p.Results We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells using qRT-PCR. Dual-luciferase reporter assay validated HIPK2 is a direct target of miR-27b-3p, confirmed by Western blot results. Pearson correlation presented that there was a significantly negative correlation between miR-27b-3p and HIPK2 mRNA. Overexpression of miR-27b-3p significantly reduced the expression of pro-apoptotic protein c-caspase3 and increased the expression of anti-apoptotic Bcl-2; however, downregulation of miR-27b-3p has a significant effect of inducing apoptosis. Furthermore, overexpression of miR-27b-3p combined with recombinant HIPK2 protein showed the inhibitory effect of miR-27b-3p was abolished by HIPK2.Conclusion We found declined miR-27b-3p and elevated HIPK2 in RA tissues and cells. Further in vitro studies demonstrated that miR-27b might inhibit chondrocyte apoptosis and thus attenuate RA development by directly inhibiting HIPK2 expression.

Background: Postoperative cognitive dysfunction (POCD) is a general complication following cardiac and major non-cardiac surgery amongst the elderly, yet its causes and mechanisms are still unknown. The present study aimed to detect whether regional cerebral blood flow (CBF) is altered in the brain before surgery in POCD patients compared with non-POCD (NPOCD) patients, thus, CBF variation may potentially predict the occurrence of early POCD.Methods: Fifty patients scheduled for spinal stenosis surgery were enrolled in the study. All study participants completed a battery of neuropsychological tests (NPTs) by a well-trained neuropsychologist before the surgery and 1 week after the surgery. POCD was defined when the preoperative to postoperative difference of at least two of the NPTs’ |Z|-scores with reference to a control group exceeded 1.96. Pulsed arterial spin-labeling (ASL) MRI was scanned at least 1 day before surgery. The ASLtbx toolkit and SPM12 were applied to preprocess and correct the images, which were then normalized to the MNI brain template space to obtain standardized cerebral perfusion images.Results: POCD was identified in 11 out of 50 patients (22%). The CBF of the right superior temporal lobe, right and left middle cingulate gyrus, and the right hippocampus, and parahippocampal gyrus in POCD group was lower than that in NPOCD group (P < 0.001). The CBF of the pars triangularis of inferior frontal gyrus in POCD group was higher than that in NPOCD group (P < 0.001).Conclusions: These preliminary findings suggest that CBF premorbid alterations may happen in cognitively intact elderly patients that develop early POCD. Alterations of preoperative CBF might be a bio-marker for early POCD that can be detected by noninvasive MRI scans.

Leukemia is the most common malignancy affecting children. The morphologic analysis of bone marrow smears is an important initial step for diagnosis. Recent publications demonstrated that artificial intelligence is able to classify blood cells but a long way from clinical use. A total of 1,732 bone marrow images were used for the training of a convolutional neural network (CNN). New techniques of deep learning were integrated and an end-to-end leukemia diagnosis system was developed by using raw images without pre-processing. The system creatively imitated the workflow of a hematologist by detecting and excluding uncountable and crushed cells, then classifying and counting the remain cells to make a diagnosis. The performance of the CNN in classifying WBCs achieved an accuracy of 82.93%, precision of 86.07% and F1 score of 82.02%. And the performance in diagnosing acute lymphoid leukemia achieved an accuracy of 89%, sensitivity of 86% and specificity of 95%. The system also performs well at detecting the bone marrow metastasis of lymphoma and neuroblastoma, achieving an average accuracy of 82.93%. This is the first study which included a wider variety of cell types in leukemia diagnosis, and achieved a relatively high performance in real clinical scenarios.

Transpiration is fundamental to the understanding of the ecophysiology of planted forests in arid ecosystems, and it is one of the most uncertain components in the ecosystem water balance. The objective of this study was to quantify differences in whole-tree transpiration estimates obtained with a heat ratio probe in a secondary Qinghai spruce (Picea crassifolia) forest. To do this, we analyzed the sap flux density values obtained with sensors installed in (1) holes drilled in the preceding growing season (treatment) and (2) holes drilled in the current year (control). The study was conducted in a catchment in the Qilian Mountains of western China. The results showed that an incomplete diameter at breast height (DBH) range contributed to 28.5% of the overestimation of the sapwood area when the DBH > 10 cm and 22.6% of the underestimation of the sapwood area when the DBH < 5 cm. At daily scales, there were significant differences in both the quantity and magnitude of the sap flux density between the treatment and control groups. Furthermore, a linear regression function (R2 = 0.96, p < 0.001), which was almost parallel to the 1:1 reference line, was obtained for the sap flux density correction for the treatment group, and the daily sap flux density and whole-tree transpiration were underestimated by 36.8 and 37.5%, respectively, at the half-hour scale. This study illustrates uncertainties and a correction function for sap flow estimations in young Qinghai spruce trees when using heat ratio sensors with minimal damage over multiple growing seasons.

In this study, we performed a retrospective and prospective study of preoperative predictors of the length of stay (LOS) in three groups of surgical patients and conducted a clinical retrospective study of the current research status of preoperative predictors of LOS prolongation in three groups of patients under ERAS (enhanced recovery after surgery) mode, such as patient characteristics and comorbidities. Information such as patients’ exercise preferences, exercise time, frequency and duration, footwear, location of knee osteoarthritis, whether there is a past history of knee injury, and smoking and drinking history was collected, and the research data of 312 patients undergoing the three operations were analyzed by SPSS. Meniscal injury-knee arthroscopy sample included a total of 104 people. Surgical sample for anterior cruciate ligament reconstruction included a total of 100 subjects. Knee osteoarthritis-knee replacement surgery sample included 148 people who were divided into two groups in a ratio of 1 : 1: one group used Mailuo Shutong pills during hospitalization (intervention group) and the other group did not (control group). The research conclusions are as follows. Meniscal Knee Arthroscopy. (1) Samples from different causes of injury showed significant differences for all injured sites. (2) Samples with different smoking and drinking histories all showed significant differences for the causes of injury. (3) Exercise hobby, exercise frequency, duration of each exercise and duration of exercise, and warm-up time before exercise all showed positive correlation. Anterior Cruciate Ligament Reconstruction Surgery. (4) Samples from different causes of injury showed significant differences for all the injured sites. (5) Age has a significant negative influence on the wearing of shoes at ordinary times. (6) Exercise hobby: the warm-up time before exercise had a significant negative influence on the injured area. (7) Two groups of analysis items of exercise frequency, exercise duration and exercise duration, preexercise warm-up time, and exercise hobby were typically positively correlated. Total Knee Arthroplasty. (8) There was a significant difference of 0.01 between the hospitalization days of the intervention group and the control group (p