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Background The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell‐cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. Methods and Results Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co‐Immunoprecipitation (Co‐IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO‐IP experiments. Results showed that the 1–265 domain of CHK1 directly binds to the 157–400 amino acids of PKM2. Furthermore, hiPSC‐CM (human iPS cell‐derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C‐domain‐mediated cardiac metabolic reprogramming. Conclusions This study demonstrates that the 1–265 amino acid domain of CHK1 binds to the 157–400 domain of PKM2 and activates PKM2‐mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Abstract Background Apatinib is an oral small‐molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor‐2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC. Methods This retrospective study included 100 human epidermal growth factor receptor‐2 (HER2)‐negative mBC patients who received low‐dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS. Results The median follow‐up time for this study was 38.1 months. Among 100 patients with HER2‐negative mBC, 66 were hormone receptor (HR)‐positive/HER2‐negative and 34 were triple‐negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2–6.8 months) and 23.0 months (95% CI, 19.9–26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR‐positive /HER2‐negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety‐five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3–4. The most common Grades 3–4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%). Conclusion Low‐dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2‐negative mBC.

Abstract Background Ovarian clear cell carcinoma (OCCC) represents a subtype of ovarian epithelial carcinoma (OEC) known for its limited responsiveness to chemotherapy, and the onset of distant metastasis significantly impacts patient prognoses. This study aimed to identify potential risk factors contributing to the occurrence of distant metastasis in OCCC. Methods Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed with OCCC between 2004 and 2015. The most influential factors were selected through the application of Gaussian Naive Bayes (GNB) and Adaboost machine learning algorithms, employing a Venn test for further refinement. Subsequently, six machine learning (ML) techniques, namely XGBoost, LightGBM, Random Forest (RF), Adaptive Boosting (Adaboost), Support Vector Machine (SVM), and Multilayer Perceptron (MLP), were employed to construct predictive models for distant metastasis. Shapley Additive Interpretation (SHAP) analysis facilitated a visual interpretation for individual patient. Model validity was assessed using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and the area under the receiver operating characteristic curve (AUC). Results In the realm of predicting distant metastasis, the Random Forest (RF) model outperformed the other five machine learning algorithms. The RF model demonstrated accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and AUC (95% CI) values of 0.792 (0.762–0.823), 0.904 (0.835–0.973), 0.759 (0.731–0.787), 0.221 (0.186–0.256), 0.974 (0.967–0.982), 0.353 (0.306–0.399), and 0.834 (0.696–0.967), respectively, surpassing the performance of other models. Additionally, the calibration curve's Brier Score (95%) for the RF model reached the minimum value of 0.06256 (0.05753–0.06759). SHAP analysis provided independent explanations, reaffirming the critical clinical factors associated with the risk of metastasis in OCCC patients. Conclusions This study successfully established a precise predictive model for OCCC patient metastasis using machine learning techniques, offering valuable support to clinicians in making informed clinical decisions.

Abstract Aim The purpose of this study was to provide a comprehensive understanding of the attitudes and experiences of the medical staff regarding the hospital bed‐sharing model. Design The present research was a qualitative study. Methods This qualitative study used in‐depth individual interviews with 7 doctors, 10 clinical nurses and 3 head nurses, which were then transcribed and analysed thematically. Results The study identified six overall themes. Issues were raised about the efficient utilization of hospital bed resources, greater challenges for nursing work, adjustment of doctors' work modes, barriers to communication between doctors, nurses, and patients, potential medical risks, and differentiation of patients' medical experience. Implications for Nursing Management Hospital administrators and nurse managers should work together to solve the challenges that medical staff face, including strengthening nursing training, improving medical–nursing collaboration models, standardizing and effective communication strategies, and improving patient experiences.

Abstract The quantum mechanisms how life efficiently utilizes energy and transmits information remain unclear yet. Frequency medicine, an emerging cross‐discipline of both quantum mechanics and biomedicine, is a promising turning point for biomaterials and medicine developing from the matter level to the energy level. Recognizing the pivotal role of molecular vibrational frequencies in resonant energy coupling and transmission underscores the potential of frequency medicine to precisely regulate biomaterial vibrations, influencing interactions and reactions in living organisms. At present, scientists have unveiled sophisticated phototherapeutics; nevertheless, their advancement necessitates the precise mapping of the life energy. In contrast to genomics, proteomics, and metabolomics studied on the matter level, omics of frequencies related to medicine should be on the energy level. Herein, starting from the history of frequency medicine, and followed by the introduction of vibrational strong coupling applications in life sciences, we emphasize the significance, necessity, and urgency of studying spatiotemporal omics of medicine frequencies. By decoding the energy atlas of life, we can acquire profound insights into the quantum mechanisms that govern life processes from an energy standpoint. We anticipate that the integration of biomaterials with spatiotemporal frequency omics related to medical research will contribute significantly to advancing the goals of precision medicine, potentially revolutionizing pharmaceuticals, such as terahertz drugs.

Objective. The objective of this study is to explore the utilization of next-generation sequencing (NGS) technology in evaluating the likelihood of identifying individuals with papillary thyroid microcarcinoma (PTMC ≤10 mm) who are at high or low risk. Design. NGS was used to analyze 393 formalin-fixed, paraffin-embedded tissues of PTC tumors, all of which were smaller than 15 mm. Results. The study found that bilateralism, multifocality, intrathyroidal spread, and extrathyroidal extension were present in 84 (21.4%), 153 (38.9%), 16 (4.1%), and 54 (13.7%) cases, respectively. Metastasis of cervical lymph nodes was identified in 226 (57.5%) cases and 96 (24.4%) cases with CLNM >5. Out of the total number of cases studied, 8 cases (2.3%) showed signs of tumor recurrence, all of which were localized and regional. Genetic alterations were detected in 342 cases (87.0%), with 336 cases revealing single mutations and 6 cases manifesting compound mutations. 332 cases (84.5%) had BRAFV600E mutation, 2 cases had KRASQ61K mutation, 2 cases had NRASQ61R mutation, 8 cases had RET/PTC1 rearrangement, 3 cases had RET/PTC3 rearrangement, and 1 case had TERT promoter mutation. Additionally, six individuals harbored concurrent mutations in two genes. These mutations were of various types and combinations: BRAFV600E and NRASQ61R (n = 2), BRAFV600E and RET/PTC3 (n = 2), BRAFV600E and RET/PTC1 (n = 1), and BRAFV600E and TERT promoter (n = 1). The subsequent analysis did not uncover a significant distinction in the incidence of gene mutation or fusion between the cN0 and cN1 patient cohorts. The presence of BRAFV600E mutation and CLNM incidence rates were found to be positively correlated with larger tumor size in PTMC. Our data showed that gene mutations did not appear to have much to do with high-risk papillary thyroid microcarcinoma (PTMC). However, when we looked at tumor size, we found that if the tumor was at least 5 millimeters in size, there was a higher chance of it being at high risk for PTM (P

Abstract Commiphora gileadensis (C. gileadensis) has been identified and linked with various health benefits and pharmaceutical potential for its phytochemical activities and chemical constituents. This study aimed to evaluate ultrasonic‐assisted extraction (USE) technique for total phenols content from C. gileadensis leaf compared to the hydrodistillation extraction (HDE). Our results showed that the USE operating conditions were identified as: MeOH·H2O solvent‐to‐fresh sample ratio of 80:20 (v/v); ultrasonic power/frequency at 150 W/20 kHz; and a temperature of 40 ± 1°C; subjected to acoustic waves intermittently for a calculated time (5 min) during the total programmed time of 12 min. The USE exhibited (118.71 ± 0.009 mg GAE/g DM) more amounts of all phenols than HDE (101.47 ± 0.005 mg GAE/g DM), and antioxidant (77.78 ± 0.73%, 75.27 ± 0.59% scavenging inhibition of DPPH), respectively. Anti‐aging and Cytotoxicity activities were investigated. The results of biological evaluations showed that the crude extracts of C. gileadensis significantly extended the replicative lifespan of K6001 yeast. In addition, in vitro cytotoxicity against the HepG2 cell line showed significant anticancer activity, and approximately 100 μg/mL is required to decrease viability compared with that of the control. This study is proven for a larger scale to extract and isolate compounds of C. gileadensis for potential utilization in the pharmaceutical industry. In conclusion, advanced methods afford an extract with high activity in the biological properties of the extract.

Abstract Background There is no consensus on the optimal regimen for unresectable recurrent hepatocellular carcinoma (HCC), so this retrospective study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and PD‐1 inhibitors (T‐L‐P) versus TACE combined with lenvatinib (T‐L) or TACE alone. Method Data were collected from 204 patients with unresectable recurrent HCC who received T‐L‐P, T‐L, or TACE alone at three medical centers from January, 2019 to December, 2020 for analysis. The survival outcomes, tumor response, and adverse events were compared between three groups, and risk factors were further investigated. Results The median overall survival in the T‐L‐P, T‐L, and TACE alone groups were not reached, 25.6, and 15.7 months, respectively (p

Abstract Sb2S3 is rapidly developed as light absorber material for solar cells due to its excellent photoelectric properties. However, the use of the organic hole transport layer of Spiro‐OMeTAD and gold (Au) in Sb2S3 solar cells imposes serious problems in stability and cost. In this work, low‐cost molybdenum (Mo) prepared by magnetron sputtering is demonstrated to serve as a back electrode in superstrate structured Sb2S3 solar cells for the first time. And a multifunctional layer of Se is inserted between Sb2S3/Mo interface by evaporation, which plays vital roles as: i) soft loading of high‐energy Mo particles with the help of cottonlike‐Se layer; ii) formation of surficial Sb2Se3 on Sb2S3 layer, and then reducing hole transportation barrier. To further alleviate the roll‐over effect, a pre‐selenide Mo target and consequentially form a MoSe2 is skillfully sputtered, which is expected to manipulate the band alignment and render an enhanced holes extraction. Impressively, the device with an optimized Mo electrode achieves an efficiency of 5.1%, which is one of the highest values among non‐noble metal electrode based Sb2S3 solar cells. This work sheds light on the potential development of low‐cost metal electrodes for superstrate Sb2S3 devices by carefully designing the back contact interface.

Abstract Aim The primary objective of this study was to assess the patient safety culture in a general hospital in Shanghai, China, through a modified Manchester Patient Safety Framework (MaPSaF). Design This study has a qualitative interview design. Data were collected through group interviews and analyses performed through content analysis. Methods The MaPSaF was translated into Chinese and used to assess the patient safety culture in a large general hospital in Shanghai, China. Group interviews using the MaPSaF were conducted with 15 nurses in the obstetric ward. Participants rated their safety practice individually on each of the nine MaPSaF safety culture dimensions. The dimensions and scores were then collectively discussed and a practice‐wide consensus score for each dimension was agreed. Discussions were recorded, transcribed and analysed to assess patient safety in the obstetric ward. Results It took about 2 hr to complete the discussion focusing on patients' safety employing the MaPSaF. Most participants recognized the process as acceptable and useful. The MaPSaF directed team discussion about patient safety issues and facilitated communication, prompting some practice changes. All participants responded positively to the discussion and perceived MaPSaF as a good safety culture assessment tool, with clear, comprehensive and understandable entries. The process demonstrated that the department of obstetrics in the hospital already had a positive patient safety culture, but certain areas were highlighted as still needing improvement. Based on participants' positive experience and perception of the MaPSaF, it can be concluded that there is potential benefit in its adaptation and use in obstetrics wards of Chinese hospitals. The MaPSaF has the potential to strengthen existing safety cultures and improve general safety through collaborative measures.

Abstract MicroRNA (miRNA) and long noncoding RNA (lncRNA) are both regulators of cancer progression. This study sought to discuss the functional mechanism of miR‐96‐5p/lncRNA TRIM52 antisense RNA 1 (head‐to‐head; TRIM52‐AS1) in cervical cancer (CC) cell resistance to cisplatin (DDP). DDP‐resistant CC cell line was established using increasing concentrations of DDP, followed by transfection with miR‐96‐5p inhibitor, or si‐TRIM52‐AS1, or insulin‐like growth factor 2 mRNA binding protein 2 (IGF2BP2) overexpression vector. Expression levels of miR‐96‐5p, TRIM52‐AS1, and IGF2BP2 were determined. Changes in IC50 value to DDP, cell proliferation, and apoptosis rate were evaluated by cell‐counting kit‐8 assay, colony formation, and flow cytometry. The bindings of miR‐96‐5p to IGF2BP2 and TRIM52‐AS1 to IGF2BP2 were verified by dual‐luciferase or RNA pull‐down assays. These experiments revealed an up‐expression of miR‐96‐5p and IGF2BP2 while an under‐expression of TRIM52‐AS1 in CC cells. After DDP treatment, miR‐96‐5p inhibition increased apoptosis and decreased proliferation and DDP resistance. miR‐96‐5p bound to TRIM52‐AS1 and downregulated TRIM52‐AS1 expression, and TRIM52‐AS1 bound to IGF2BP2 to inhibit IGF2BP2 expression. TRIM52‐AS1 inhibition or IGF2BP2 overexpression neutralized the inhibition of silencing miR‐96‐5p on CC cell resistance to DDP. Overall, miR‐96‐5p improved CC cell resistance to DDP by inhibiting TRIM52‐AS1 and promoting IGF2BP2.

Abstract Aims Medication‐taking behaviours of breast cancer survivors undergoing adjuvant hormone therapy have received considerable attention. This study aimed to determine factors affecting medication‐taking behaviours in people with breast cancer using data mining. Design A longitudinal observational retrospective cohort study with a hospital‐based survey. Methods A total of 385 subjects were surveyed, analysing existing data from January 2010 to December 2017 in Taiwan. Three data mining approaches—multiple logistic regression, decision tree and artificial neural network—were used to build the prediction models and rank the importance of influencing factors. Accuracy, specificity and sensitivity were used as assessment indicators for the prediction models. Results Multiple logistic regression was the most effective approach, achieving an accuracy of 96.37%, specificity of 96.75% and sensitivity of 96.12%. The duration of adjuvant hormone therapy discontinuation, duration of adjuvant hormone therapy use and age at diagnosis by data mining were the three most critical factors influencing the medication‐taking behaviours of people with breast cancer.

Abstract Nonsmall‐cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR‐455‐3p, and HDAC2 was explored by dual‐luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR‐455‐3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)‐mutant NSCLC cells. Moreover, inhibition of miR‐455‐3p exhibited the opposite effect. CRNDE bound with miR‐455‐3p, and HDAC2 was found to be targeted by miR‐455‐3p. Meanwhile, miR‐455‐3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR‐455‐3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR‐455‐3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.

Abstract Excessive proliferation and migration of airway smooth muscle cell (ASMC) contribute to asthma pathogenesis. Long noncoding RNAs (lncRNAs) are reported to take part in asthma pathogenesis. This study is targeted at deciphering the role of the lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) in ASMC proliferation, migration and extracellular matrix (ECM) deposition. qRT‐PCR was performed to determine ANRIL, miR‐98‐5p, and cyclin D1 (CCND1) mRNA expression levels in transforming growth factor‐β1 (TGF‐β1)‐treated ASMCs. CCK‐8 and Transwell assays were employed to examine ASMC proliferation and migration, respectively. Dual‐luciferase reporter gene assay and RNA immunoprecipitation assay were carried out for analyzing the targeted relationship of miR‐98‐5p with ANRIL or CCND1 mRNA 3′‐UTR. The levels of CCND1 and ECM proteins (such as fibronectin, COL3A1, and COL1A2) in ASMCs were detected through Western blot. In this work, we found that ANRIL and CCND1 were up‐regulated in TGF‐β1‐treated ASMCs, whereas miR‐98‐5p was down‐regulated. ANRIL overexpression facilitated the proliferation, ECM deposition and migration of TGF‐β1‐induced ASMCs, while knocking down ANRIL had the opposite effect. Furthermore, ANRIL targeted miR‐98‐5p directly, and CCND1 was miR‐98‐5p's downstream target. ANRIL indirectly increased CCND1 expression in ASMCs via competitively binding to miR‐98‐5p. MiR‐98‐5p inhibition or CCND1 overexpression counteracted the inhibiting effect that ANRIL knockdown had on TGF‐β1‐stimulated ASMC proliferation, migration and ECM deposition. In conclusion, ANRIL indirectly up‐regulates CCND1 expression by targeting miR‐98‐5p to promote ASMC proliferation, migration and ECM deposition, thus facilitating the pathogenesis of asthma.

Abstract Droplet arrays show great significance in biosensing and biodetection because of low sample consumption and easy operation. However, inevitable water evaporation in open environment severely limits their applications in time‐consuming reactions. Herein, inspired by the unique water retention features of leaves, it is demonstrated that an open droplet array on patterned organohydrogel surface with water evaporating replenishment (POWER) for ultrawide time‐range biosensing, which integrated hydrophilic hydrogel domains and hydrophobic organogel background. The hydrogel domains on the surface can supply water to the pinned droplets through capillary channels formed in the nether organohydrogel bulk. The organogel background can inhibit water evaporation like the wax coating of leaves. Such a unique bioinspired design enables ultrawide time‐range biosensing in open environment from a few minutes to more than five hours involving a variety of analytes such as ions, small molecules, and macromolecules. The POWER provides a feasible and open biosensing platform for ultrawide time‐range reactions.

Abstract Electrochemical oxygen reduced reaction (ORR) is a critical element in clean energy development. Despite efforts to enhance gas transfer to the reaction interface, the low solubility of O2 molecules and slow diffusion rate in liquid electrolyte is still a significant challenge. Herein, we design an artificial outer membrane on microalgal cells, which consists of a carbon dots/bilirubin oxidase (CDs/BOD) ORR catalyst layer and a L‐cystine/Au nanoporous O2 supply layer. O2 generated by photosynthesis from microalgal cells then can be directly transported to the CDs/BOD catalytic interfaces, overcoming the sluggish gas transfer in the electrolyte. Thus, the cathode constructed by the fabricated microalgal cells realizes an ORR current density of 655.2 μA/cm2 with fast ORR kinetics, which is 2.68 times higher than that of a BOD cathode fed with pure O2. A membrane‐less glucose/O2 biofuel cell is further developed using the hybrid artificial cells as the cathode, and the power density is 2.39 times higher than that of a BOD cathode biofuel cell in O2 saturated solution. This biomimetic design supplies O2 directly to the carbon dots/BOD catalyst layer from the microalgae membrane through a nanoporous L‐cys/Au layer, providing an alternative solution for the transfer barrier of O2 in the electrolyte.

In this paper, we propose a modified version of the hard thresholding pursuit algorithm, called modified hard thresholding pursuit (MHTP), using a convex combination of the current and previous points. The convergence analysis, finite termination properties, and stability of the MHTP are established under the restricted isometry property of the measurement matrix. Simulations are performed in noiseless and noisy environments using synthetic data, in which the successful frequencies, average runtime, and phase transition of the MHTP are considered. Standard test images are also used to test the reconstruction capability of the MHTP in terms of the peak signal-to-noise ratio. Numerical results indicate that the MHTP is competitive with several mainstream thresholding and greedy algorithms, such as hard thresholding pursuit, compressive sampling matching pursuit, subspace pursuit, generalized orthogonal matching pursuit, and Newton-step-based hard thresholding pursuit, in terms of recovery capability and runtime.

Knowing the stability of drugs is important to ensure accurate and reliable results of drug concentrations. This study evaluated the stability of ten new psychoactive substances (NPSs) in urine and methanol/water at different storage temperatures. Quantitative analyses were performed using liquid chromatography-tandem mass spectrometry. Three replicates of each storage condition were analyzed at day 0 and after 7, 14-, 30-, 60-, and 90 days with storage at +25°C, +4°C, and −20°C. For each analyte, the percent difference at each time interval from day 0 was calculated for each storage condition. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), deschloroketamine (DCK), and 2-fluorodeschloroketamine (2-FDCK) were stable in urine, even when stored for 90-day periods at various temperatures. For synthetic cathinones, the concentrations declined over time at room temperature (+25°C) in urine but were relatively stable in methanol solvent with 0.1% formic acid. The significant degradation was found at +25°C, and the most excellent stability was shown by samples stored at −20°C. Phenethylamines (PMA and PMMA) and ketamine substitutes (DCK and 2-FDCK) were relatively more stable than synthetic cathinones (mephedrone, butylone, pentylone, ephylone, 4-MEAPP, and eutylone).

Aim. We sought to profile gut microbiota’s role in combination of Bu Fei Hua Yu (BFHY) with cisplatin treatment. Methods. Non-small cell lung cancer (NSCLC) mice model were constructed followed by treatment with cisplatin alone or combined with BFHY. Mice weight and tumor volume were measured during the experiment. And mice cecum were detected by hematoxylin and eosin, cecum contents were collected for Enzyme Linked ImmuneSorbent Assay, and stool were profiled for metagenomic sequencing. Results. Combination of BFHY with cisplatin treatment decreased the tumor growth and relieved the damage of cecum. Expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP), and interferon-γ (IFN-γ) were decreased compared with cisplatin treatment alone. Linear discriminant analysis effect size analysis showed that g_Parabacteroides was downregulated and g_Escherichia and g_Blautia were upregulated after cisplatin treatment. After combination with BFHY, g_Bacteroides and g_Helicobacter were decreased. g_Klebsiella, g_Unclssified_Proteobacteria, and g_Unclssified_Clostridiates were increased. Moreover, heatmap results showed that Bacteroides abundance was increased significantly after cisplatin treatment; BFHY combination treatment reversed this state. Function analysis revealed that multiple functions were slightly decreased in cisplatin treatment alone and increased significantly after combination with BFHY. Conclusion. Our study provided evidence of an efficacy of combination of BFHY with cisplatin on treatment of NSCLC and revealed that gut microbiota plays a role in it. The above results provide new ideas on NSCLC treatment.

Abstract Background The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown. Aims To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. Materials & Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain‐ and loss‐of‐function assays. RNA pull‐down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients. Results In this study, we show that the long non‐coding RNA BC009639 (BC) is involved in acquired resistance to EGFR‐targeted therapies. Among the 235 long non‐coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR‐TKI therapy. To uncover the molecular mechanism of BC‐mediated EGFR‐TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non‐protein‐coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein‐coding variant. The BC‐mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial–mesenchymal transition and resistance to EGFR‐TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD. Disscussion Through alternative splicing, BC boosted the non‐coding IMPAD1‐203 transcript variant while suppressing the IMPAD1‐201 variant. In order to control the processing of pre‐mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing‐regulator complex by creating RNA‐RNA‐duplexes. Conclusion Our results reveal an important role for BC in mediating resistance to EGFR‐targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance.

Objective To evaluate knee scores and clinical efficacies of patients with non‐lateral unicompartmental knee osteoarthritis (OA) who randomly underwent mobile‐bearing (MB) unicompartmental knee arthroplasty (UKA), fixed‐bearing (FB) UKA, and total knee arthroplasty (TKA). Methods From September 2015 to February 2017, a prospective, randomized, parallel, single‐center trial of 180 patients (78 males and 102 females; 63.3 ± 6.9 years) with non‐lateral compartmental knee OA was performed in the first author‐affiliated hospital. The patients were randomly divided into three groups (each group included 60 patients) and received medial cemented Oxford phase 3 MB UKA, medial cemented Link FB UKA, or cemented DePuy Sigma PFC TKA, respectively. A similar perioperative management and fast‐track surgery program was carried out for all patients. The knee scores at 3‐year follow‐up after operation and clinical efficacies of these three groups of patients were recorded, investigated, and compared. Results Primarily, compared to the TKA group, the UKA groups (MB UKA and FB UKA) had shorter operative time (median 63.2 74.5) (P = 0.007), better results in all knee scores (except VAS and KSS function scores) (P 96.0°) (P = 0.001). Secondarily, compared to the TKA group, the MB UKA group showed better results in the Western Ontario and McMaster Universities index (WOMAC) stiffness (83.6 > 79.6), WOMAC total (86.3 > 83.2), Oxford knee score (OKS) (20.0 74.5), and a larger maximum flexion angle of the knee (123.0 > 96.0) (P 88.5), WOMAC stiffness (84.3 > 79.6), WOMAC function (85.2 > 81.7), WOMAC total scores (87.6 > 83.2), and a larger maximum flexion angle of the knee (119.0° > 96.0°) than the TKA group (P 0.05). There was one case with original bearing dislocation in MB UKA group. One patient with displacement of the femoral component caused by a fall injury, and another patient, who lost his life in a car accident, were involved in the FB UKA group. There was an infection case and an intermuscular vein thrombosis case in TKA group. Conclusion UKA showed more advantages than TKA; however, there was no significant difference between the MB UKA and FB UKA groups for treatment of non‐lateral compartmental knee OA.

Objectives To propose an updated definition of proximal tibia and fibula fracture (PTFF) and establish a three‐dimensional (3D) structure‐based classification of PTFF. Methods In total, 1358 adult patients (837 males and 521 females; 43.61 ± 15.13 years， 1364 affected knees) who were diagnosed with PTFF at the departments of orthopaedic surgery of four hospitals from January 2010 to December 2019 were enrolled. The new classification of PTFF, termed Wu classification, included three parts: classification of columns in the horizontal plane, regions in the frontal plane, and segments in the sagittal plane. All PTFFs were classified according to Schatzker, Luo, and Wu classification systems. Additionally, the incidence and characteristics of PTFFs were analyzed. Results The major internal structural fractures of PTFF were tibial plateau fracture (TPF) only (725, 53.15%), TPF and proximal fibular fracture (274, 20.09%), and isolated avulsion fracture of the posterior cruciate ligament (PCL) (189, 13.86%). Approximately a quarter of PTFF cases could not be classified using Schatzker or Luo classifications, but all PTFF cases could be classified using Wu classification. The most frequent PTFFs included all four columns in region IV, segment 2 (235, 17.23%); the posterolateral and posteromedial columns in region II, segment 2 (191, 14.00%); and the lateral and posterolateral columns in region IV, segment 2 (136, 9.97%). Isolated avulsion fracture of the anterior cruciate ligament (ACL) was categorized as three injury types, most of which involved the lateral and medial columns in region II, segment 1 (40/63, 64%). More than 97% of cases of isolated fractures of the PCL involved the posterolateral and posteromedial columns in region II, segment 2. The most frequent combined avulsion fracture of the ACL and PCL included all four columns in region II, segment 2 (18/24, 75%). All of the isolated avulsion fractures of the ACL were located in segment 1, and all those of the PCL in segment 2. The most common type of isolated proximal fibular fracture involved the posterolateral column in region III, segment 2 (23/26, 88%). The most frequent combined TPF and proximal fibular fracture involved all four columns in region IV, segment 2 (107/274, 39.05%). Conclusions All cases of PTFF could be classified by the new 3D Wu classification which should be beneficial for clinical diagnosis, guidance of treatment, statistical analysis, academic communication, and prognosis, and the most frequent PTFF involved all four columns in region IV, segment 2.

Abstract Background As an autoimmune systemic disorder, rheumatoid arthritis (RA) features chronic inflammation as well as synovial infiltration of immune cells. This study was designed with the purpose of discussing the hidden mechanism of SPTBN1 and exploring favorable molecular‐targeted therapies. Methods With the application of RT‐qPCR and western blot, the expressions of SPTBN1 and PIK3R2 before or after transfection were estimated. Besides, Cell Counting Kit‐8, Edu, wound healing, transwell, enzyme‐linked immunosorbent assay, and TUNEL were adopted for the evaluation of the viability, proliferation, migration, invasion, inflammatory response, and apoptosis of fibroblast‐like synoviocyte (FLS). In addition, the interaction of SPTBN1 and PIK3R2 was testified by applying immunoprecipitation (IP) and western blot was utilized for the assessment of migration‐, apoptosis‐, and PI3K/AKT signal‐related proteins. Results It was discovered that SPTBN1 declined in RA synovial cells and its overexpression repressed the proliferation, migration, invasion, and inflammation of RA‐FLSs but promoted apoptosis. IP confirmed that SPTBN1 could bind to PIK3R2 in FLSs. To further figure out the hidden mechanism of SPTBN1 in RA, a series of functional experiments were carried out and the results demonstrated that the reduced expressions of MMP2, MMP9, IL‐8, IL‐1β, IL‐6, and Bcl2 as well as increased levels of Bax and cleaved caspase3 in SPTBN1‐overexpressed RA‐FLSs were reversed by PIK3R2 depletion, revealing that SPTBN1 repressed the migration and inflammation and promoted the apoptosis of RA‐FLSs via binding to PIK3R2. Results obtained from western blot also revealed that PIK3R2 interference ascended the contents of p‐PI3K and p‐AKT in SPTBN1‐overexpressed RA‐FLSs, implying that SPTBN1 repressed PI3K/AKT signal in RA via PIK3R2. Discussion SPTBN1 alleviated the proliferation, migration, invasion, and inflammation in RA via interacting with PIK3R2.

Background The change of cardiovascular health (CVH) status has been associated with risk of cardiovascular disease. However, no studies have explored the change patterns of CVH in relation to risk of sudden cardiac death (SCD). We aim to examine the link between baseline CVH and change of CVH over time with the risk of SCD. Methods and Results Analyses were conducted in the prospective cohort ARIC (Atherosclerosis Risk in Communities) study, started in 1987 to 1989. ARIC enrolled 15 792 individuals 45 to 64 years of age from 4 US communities (Forsyth County, North Carolina; Jackson, Mississippi; suburbs of Minneapolis, Minnesota; and Washington County, Maryland). Subjects with 0 to 2, 3 to 4, and 5 to 7 ideal metrics of CVH were categorized as having poor, intermediate, or ideal CVH, respectively. Change in CVH over 6 years between 1987 to 1989 and 1993 to 1995 was considered. The primary study outcome was physician adjudicated SCD. The study population consisted of 15 026 subjects, of whom 12 207 had data about CVH change. Over a median follow‐up of 23.0 years, 583 cases of SCD were recorded. There was a strong inverse association between baseline CVH metrics and time varying CVH metrics with risk of SCD. Compared with subjects with consistently poor CVH, risk of SCD was lower in those changed from poor to intermediate/ideal (hazard ratio [HR], 0.67 [95% CI, 0.48–0.94]), intermediate to poor (HR, 0.73 [95% CI, 0.54–0.99]), intermediate to ideal (HR, 0.49 [95% CI, 0.24–0.99]), ideal to poor/intermediate CVH (HR, 0.23 [95% CI, 0.10–0.52]), or those with consistently intermediate (HR, 0.49 [95% CI, 0.36–0.66]) or consistently ideal CVH (HR, 0.31 [95% CI, 0.13–0.76]). Similar results were also observed for non‐SCD. Conclusions Compared with consistently poor CVH, other patterns of change in CVH were associated with lower risk of SCD. These findings highlight the importance of promotion of ideal CVH in the primordial prevention of SCD.