Assessment of the implementation of accelerated drug marketing registration procedures for antineoplastic and immunomodulating agents in China: based on 2016-2022 review data.

Objective: Since 2016, China has successively implemented Accelerated Drug Marketing Registration Procedures (ADMRPs) for drugs, including Breakthrough Therapy Drug (BTD), Conditional Approval (CA), and Priority Review and Approval (PRA), which have played an important role in promoting the development and review of clinically urgently needed drugs. In this study, we focused on the antineoplastic and immunomodulating agents approved for marketing through ADMRPs, to provide a reference for promoting the formation of a stable and mature regulatory system for the review and approval of antineoplastic drugs and immunomodulating agents in China. Methods: Reviewed the National Medical Products Administration (NMPA) drug review reports for the years 2016-2022 and screened the antineoplastic and immunomodulating agents approved through ADMRPs. Then, with the help of the NMPA website and the Yaozhi Database, two researchers independently queried and entered the detailed information of the selected drugs, and checked with each other. The attribute classification and main characteristics of the drugs were then analyzed with descriptive statistics to obtain the trend of drug types, drug review and approval status, and timeliness. Results: A total of 206 antineoplastic and immunomodulating agents were approved for marketing through five accelerated marketing registration procedures (or procedure combinations), with the average review time shortened by about 81 days. Among them, imported drugs accounted for a larger proportion, the most drugs for treating non-small cell lung cancer and lymphoma, and the largest number of PD-1/PDL-1 inhibitors, but pediatric drugs and rare disease drugs accounted for a smaller proportion. Conclusion: ADMRPs can promote the accessibility of antineoplastic and immunomodulating agents in China and safeguard the life and health rights of more patients. Nevertheless, it is necessary to pay attention to the expansion of the types of indications for medicines and to increase the development of drugs that are urgently needed by a small number of patients.

CEUS in prediction of early recurrence of hepatocellular carcinoma after curative resection and to stratify the risk of early recurrence: a retrospective observational study.

PURPOSE: Early recurrence (ER) after surgery is related to early death in patients with hepatocellular carcinoma (HCC) after radical resection. To explore the role of preoperative contrast-enhanced ultrasound (CEUS) in predicting ER of HCC after curative resection and to stratify the risk of ER. MATERIALS AND METHODS: This study evaluated consecutive 556 patients with HCC who were examined by CEUS during the 2 weeks before curative resection between January 2011 and December 2018. ER was defined as intrahepatic and/or extrahepatic recurrence within 2 year after resection of HCC. Univariate and logistic regression analyses were performed to identify independent risk factors for ER after surgical resection of HCC. Recurrence-free time (RFS) rates were analyzed and compared by log-rank test. RESULTS: ER occurred in 307 (55.2%) of the 556 patients. Univariate and multivariate analyses revealed that a tumor size ≥ 30 mm and satellite nodules seen on CEUS, DL(deep learning) radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level were significantly associated with ER (P < .05). Based on the number of predictors present, patients with CEUS LR-5 HCC were stratified into three risk subgroups: risk group 3 (high-risk patients, 4 predictors), risk group 2 (medium-risk patients, 2-3 predictors), and risk group 1 (low-risk patients, 0-1 predictor). The 2-year RFS rate was 19.4% in risk group 3, 40.9% in risk group 2, and 48.1% in risk group 1; the corresponding mean RFS times were 14.0 ± 2.9 months, 43.7 ± 6.6 months, and 55.5 ± 2.8 months, respectively (P < .001). CONCLUSIONS: Tumor size ≥ 30 mm and satellite nodules seen on CEUS, DL radiomics reoccurrence score based on the frame of image with the maximum intensity of CEUS and an elevated alpha-fetoprotein level can predict ER of HCC.

Estimated pulse wave velocity and risk of new-onset heart failure.

AIMS: As a potential surrogate of carotid-femoral pulse wave velocity, estimated pulse wave velocity (ePWV) has been confirmed to independently predict the cardiovascular events, but the association between ePWV and heart failure has not been well confirmed. Therefore, we performed this cohort study to evaluate the association between ePWV and risk of new-onset heart failure. METHODS AND RESULTS: A total of 98 269 employees (mean age: 51.77 ± 12.56 years, male accounted for 79.9%) without prior heart failure who participated in the 2006-2007 health examination were selected as the observation cohort, with an average follow-up of 13.85 ± 1.40 years. Area under the receiver operator characteristic curve (AUC) of ePWV was calculated in prediction of heart failure. The adjusted Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals. The category-free net reclassification index (NRI) was calculated to evaluate the reclassification performance of cardiovascular risk models after adding ePWV. The AUC of ePWV was 0.74 in prediction of heart failure. After adjusting for the traditional cardiovascular risk factors except for age and blood pressure, the risk of new-onset heart failure increased by 35% [hazard ratio (HR): 1.35, 95% confidence interval (CI): 1.33-1.37] for each 1 m/s increase in ePWV. Subgroup analysis showed that ePWV was significantly associated with incident heart failure regardless of THE presence (HR: 1.33, 95% CI: 1.31-1.36, P < 0.01) or absence (HR: 1.59, 95% CI: 1.46-1.73, P < 0.01) of cardiovascular risk factors, male (HR: 1.33, 95% CI: 1.31-1.36, P < 0.01) or female (HR: 1.44, 95% CI: 1.38-1.51, P < 0.01), young and middle-aged (<52 years) (HR: 1.50, 95% CI: 1.41-1.58, P < 0.01), or middle-aged and elderly (≥52 years) (HR: 1.23, 95% CI: 1.21-1.26, P < 0.01). The addition of ePWV to the traditional cardiovascular risk model including age and mean arterial pressure could significantly improve the reclassification ability by 31.1% (category-free NRI = 0.311, P < 0.01). CONCLUSIONS: ePWV was an independent predictor for new-onset heart failure.

Epidemiological characteristics of human- and chicken-derived CTX-M-type extended-spectrum ß-lactamase-producing Escherichia coli from China.

Bacterial resistance to ß-lactams is mainly attributed to CTX-M-type extended-spectrum ß-lactamases (ESBLs). However, the predominant sequence type (ST) of blaCTX-M-carrying Escherichia coli (blaCTX-M-Ec) in chickens, an important food animal, in China and its contribution to human ß-lactam resistance are not investigated. In this study, approximately 1808 chicken-derived strains collected from 10 provinces from 2012 to 2020 were screened for blaCTX-M-Ec, and 222 blaCTX-M-Ec were identified. Antimicrobial susceptibility tests, whole genome sequencing and conjugation experiment were performed. All quality-controlled 136 chicken-derived blaCTX-M-Ec and 1193 human-derived blaCTX-M-Ec genomes were downloaded from NCBI and EnteroBase to comprehensively analyze the prevalence of blaCTX-M-Ec in China. blaCTX-M-55 (153/358, 42.7% in chicken isolates; 312/1193, 26.2% in human isolates) and blaCTX-M-14 (92/358, 25.7% in chicken isolates; 450/1193, 37.7% in human isolates) were dominant in blaCTX-M-Ec. The STs of blaCTX-M-Ec were diverse and scattered, with ST155 (n = 21) and ST152 (n = 120) being the most abundant in chicken- and human-derived isolates, respectively. Few examples indicated that chicken- and human-derived blaCTX-M-Ec have 10 or less core genome single nucleotide polymorphisms (cgSNPs). Genetic environment analysis indicated that ISEcp1, IS26 and IS903B were closely associated with blaCTX-M transfer. The almost identical pc61-55 and pM-64-1161 indicated the possibility of plasmid-mediated transmission of blaCTX-M between humans and chickens. Although the genomes of most blaCTX-M-Ec isolated from chickens and humans were quite different, the prevalence and genetic environment of blaCTX-M variants in both hosts were convergent. CTX-M-mediated resistance is more likely to spread through horizontal gene transmission than bacterial clones.

Inhibition of α-glucosidase activity and intestinal glucose transport to assess the in vivo anti-hyperglycemic potential of dodecyl-acylated phlorizin and polydatin derivatives.

A diet containing natural active compounds that can inhibit the hydrolytic activity of α-glucosidase on carbohydrates and intestinal glucose absorption is an effective means of controlling postprandial hyperglycemia. Phlorizin and polydatin as phenolic glycosides have a high affinity for the catalytic site of α-glucosidase, but exhibited unsatisfactory competitive inhibitory capacity, with an IC50 of 0.97 and >2 mM, respectively. However, dodecyl-acylated derivatives of phlorizin and polydatin exerted α-glucosidase inhibitory capacity, with an IC50 of 55.10 and 70.95 µM, respectively, which were greatly enhanced and much stronger than that of acarbose with an IC50 of 2.46 mM. The SPR assay suggested the high affinity of dodecyl phlorizin and dodecyl polydatin to α-glucosidase with equilibrium dissociation constant (KD) values of 12.0 and 7.9 µM, respectively. Both dodecyl phlorizin and dodecyl polydatin reduced the catalytic ability of α-glucosidase by reversible noncompetitive and uncompetitive mixed inhibition, which bind noncovalently to the allosteric site 2 through hydrogen bonds and hydrophobic interactions, thereby inducing the secondary structure unfolding and intrinsic fluorescence quenching of α-glucosidase. Confocal microscopy detection visually showed significant inhibitory effects on FITC-labeled glucose uptake in intestinal Caco-2 cells by phlorizin, polydatin, dodecyl phlorizin and dodecyl polydatin. In addition, based on the differentiated Caco-2 cell monolayer model, dodecyl phlorizin and dodecyl polydatin suppressed intestinal glucose transport more effectively than phlorizin and polydatin, suggesting that they were promising in vivo hypoglycemic active compounds.

Advances in Polysaccharides for Cartilage Tissue Engineering Repair: A Review.

Cartilage repair has been a significant challenge in orthopedics that has not yet been fully resolved. Due to the absence of blood vessels and the almost cell-free nature of mature cartilage tissue, the limited ability to repair cartilage has resulted in significant socioeconomic pressures. Polysaccharide materials have recently been widely used for cartilage tissue repair due to their excellent cell loading, biocompatibility, and chemical modifiability. They also provide a suitable microenvironment for cartilage repair and regeneration. In this Review, we summarize the techniques used clinically for cartilage repair, focusing on polysaccharides, polysaccharides for cartilage repair, and the differences between these and other materials. In addition, we summarize the techniques of tissue engineering strategies for cartilage repair and provide an outlook on developing next-generation cartilage repair and regeneration materials from polysaccharides. This Review will provide theoretical guidance for developing polysaccharide-based cartilage repair and regeneration materials with clinical applications for cartilage tissue repair and regeneration.

Clinical evidence for efficacy of pembrolizumab in MSI-H and TMB-H advanced solid tumor: results from three cancer centers in China.

BACKGROUND: Pembrolizumab has been indicated in the treatment of solid tumors with high frequency microsatellite instability (MSI-H) or high tumor mutational burden (TMB-H); however, real-world data on the effectiveness of pembrolizumab with or without chemotherapy in this molecular subset remain limited. Our retrospective study evaluated the clinical efficacy and safety of pembrolizumab in treating advanced solid tumors with either MSI-H or TMB-H. METHODS: This retrospective study analyzed data from 116 patients with MSI-H or TMB-H advanced solid cancers who received pembrolizumab with or without chemotherapy regardless of treatment setting. We analyzed objective response rate (ORR) and progression-free survival (PFS). RESULTS: The top three cancer types were colorectal (48.6% MSI-H, 6.5% TMB-H), lung (15.4% MSI-H, 84.4% TMB-H), and gastric (15.4% MSI-H, 5.1% TMB-H). The ORR with pembrolizumab was 52.6%, including complete response (CR) observed in 8.6% (n = 10) of cases and partial responses (PR) in 43.9% (n = 51). Of the 93 patients who received first-line pembrolizumab, 52 patients achieved objective response (10 CR, 42 PR), with a median PFS of 14.0 months (95% confidence intervals [CI] 6.6-21.4). Of the 23 who received subsequent-line pembrolizumab, the ORR was 39.1%, disease control rate was 91.3%, and median PFS was 5.7 months (95% CI 3.9-7.5). Treatment-related adverse events were observed in 32 patients (27.6%), with no reported treatment-related fatal adverse events. CONCLUSION: Our study provides real-world evidence on the clinical effectiveness of pembrolizumab with or without chemotherapy in the treatment of patients with MSI-H and TMB-H advanced solid cancers.

Liver resection versus microwave ablation for solitary and small (≤ 3 cm) HCC with early recurrence in different stages of liver cirrhosis: A propensity score matching study.

BACKGROUND: This study aimed to compare the effectiveness of liver resection (LR) and microwave ablation (MWA) in hepatocellular carcinoma (HCC) patients with early recurrence and varying stages of cirrhosis. METHOD: This study analyzed patients with HCC who underwent hepatectomy and experienced early tumor recurrence (≤3 cm) between December 2002 and December 2020 at the Tongji Hospital. Treatment effectiveness was assessed using a propensity score matching (PSM) analysis. RESULTS: This study included 295 patients (106, LR; 189, MWA), 86 patients in each of the 2 groups were chosen for further comparison, after PSM. After PSM, both LR and MWA demonstrated similar recurrence-free survival (RFS) and overall survival (OS) rates (p = 0.060 and p = 0.118, respectively). However, the LR group had more treatment-related complications. In patients with moderate or severe cirrhosis, no significant differences in RFS or OS rates were found between the LR and MWA groups (p = 0.779 and p = 0.772, respectively). In patients without cirrhosis or with mild cirrhosis, LR showed better RFS and OS rates than MWA (p = 0.024 and p = 0.047, respectively). Multivariate analysis after PSM identified moderate or severe cirrhosis and recurrence intervals ≤12 months as independent predictors of poor RFS and OS in patients with early recurrence of HCC. CONCLUSION: LR is more effective than MWA for early recurrence of HCC in patients without cirrhosis or with mild cirrhosis, showing improved RFS and OS rates. In patients with moderate or severe cirrhosis, the OS and RFS were statistically equal between the two therapies. However, MWA may be preferred owing to its low complication rate.

Integrated metabolomics revealed the photothermal therapy of melanoma by Mo2C nanosheets: toward rehabilitated homeostasis in metabolome combined lipidome.

Melanoma, the most aggressive and life-threatening form of skin cancer, lacks innovative therapeutic approaches and deeper bioinformation. In this study, we developed a photothermal therapy (PTT) based on Mo2C nanosheets to eliminate melanoma while utilizing integrated metabolomics to investigate the metabolic shift of metabolome combined lipidome during PTT at the molecular level. Our results demonstrated that 1 mg ml-1 Mo2C nanosheets could efficiently convert laser energy into heat with a strong and stable photothermal effect (74 ± 0.9 °C within 7 cycles). Furthermore, Mo2C-based PTT led to a rapid decrease in melanoma volume (from 3.299 to 0 cm2) on the sixth day, indicating the effective elimination of melanoma. Subsequent integrated metabolomics analysis revealed significant changes in aqueous metabolites (including organic acids, amino acids, fatty acids, and amines) and lipid classes (including phospholipids, lysophospholipids, and sphingolipids), suggesting that melanoma caused substantial fluctuations in both metabolome and lipidome, while Mo2C-based PTT helped improve amino acid metabolism-related biological events (such as tryptophan metabolism) impaired by melanoma. These findings suggest that Mo2C nanosheets hold significant potential as an effective therapeutic agent for skin tumors, such as melanoma. Moreover, through exploring multidimensional bioinformation, integrated metabolomics technology provides novel insights for studying the metabolic effects of tumors, monitoring the correction of metabolic abnormalities by Mo2C nanosheet therapy, and evaluating the therapeutic effect on tumors.

Ultra-selective uranium separation by in-situ formation of π-f conjugated 2D uranium-organic framework.

With the rapid development of nuclear energy, problems with uranium supply chain and nuclear waste accumulation have motivated researchers to improve uranium separation methods. Here we show a paradigm for such goal based on the in-situ formation of π-f conjugated two-dimensional uranium-organic framework. After screening five π-conjugated organic ligands, we find that 1,3,5-triformylphloroglucinol would be the best one to construct uranium-organic framework, thus resulting in 100% uranium removal from both high and low concentration with the residual concentration far below the WHO drinking water standard (15 ppb), and 97% uranium capture from natural seawater (3.3 ppb) with a record uptake efficiency of 0.64 mg·g-1·d-1. We also find that 1,3,5-triformylphloroglucinol can overcome the ion-interference issue such as the presence of massive interference ions or a 21-ions mixed solution. Our finds confirm the superiority of our separation approach over established ones, and will provide a fundamental molecule design for separation upon metal-organic framework chemistry.

CSF 14-3-3 zeta(ζ) isoform is associated with tau pathology and cognitive decline in Alzheimer's disease.

14-3-3 is a family of conserved proteins that consist of seven isoforms which are highly expressed in the brain, and 14-3-3 zeta(ζ) is one of the isoforms encoded by the YWHAZ gene. Previous studies demonstrated that 14-3-3ζ is deposited in the neurofibrillary tangles of Alzheimer's disease (AD) brains, and that 14-3-3ζ interacts with tau from the purified neurofibrillary tangles of AD brain extract. The present study examined the cerebrospinal fluid (CSF) 14-3-3ζ levels of 719 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI), including cognitively normal (CN) participants, patients with mild cognitive impairment (MCI) and patients with AD dementia, and aimed to identify whether CSF 14-3-3ζ is associated with tau pathology. CSF 14-3-3ζ levels were increased in AD, and particularly elevated among tau pathology positive individuals. CSF 14-3-3ζ levels were associated with CSF phosphorylated tau 181 (p-tau) (r = 0.741, P < 0.001) and plasma p-tau (r = 0.293, P < 0.001), which are fluid biomarkers of tau pathology, and could predict tau pathology positive status with high accuracy (area under the receiver operating characteristic curve [AUC], 0.891). CSF 14-3-3ζ levels were also correlated to synaptic biomarker CSF GAP-43 (r = 0.609, P < 0.001) and neuroinflammatory biomarker CSF sTREM-2 (r = 0.507, P < 0.001). High CSF 14-3-3ζ levels at baseline were associated with progressive decline of cognitive function and neuroimaging findings during follow up. In conclusion, this study suggests that CSF 14-3-3ζ is a potential biomarker of AD that may be useful in clinical practice.

Wireless facial biosensing system for monitoring facial palsy with flexible microneedle electrode arrays.

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Hybrid visual and memory search for scenes and objects with variable viewpoints.

In hybrid search, observers search visual arrays for any of several target types held in memory. The key finding in hybrid search is that response times (RTs) increase as a linear function of the number of items in a display (visual set size), but RTs increase linearly with the log of the memory set size. Previous experiments have shown this result for specific targets (find exactly this picture of a boot on a blank background) and for broad categorical targets (find any animal). Arguably, these are rather unnatural situations. In the real world, objects are parts of scenes and are seen from multiple viewpoints. The present experiments generalize the hybrid search findings to scenes (Experiment 1) and multiple viewpoints (Experiment 2). The results replicated the basic pattern of hybrid search results: RTs increased logarithmically with the number of scene photos/categories held in memory. Experiment 3 controls the experiment for which viewpoints were seen in an initial learning phase. The results replicate the findings of Experiment 2. Experiment 4 compares hybrid search for specific viewpoints, variable viewpoints, and categorical targets. Search difficulty increases from specific viewpoints to variable viewpoints and then to categorical targets. The results of the four experiments show the generality of logarithmic search through memory in hybrid search.

Fabrication of Multi-Layered Paper-Based Supercapacitor Anode by Growing Cu(OH)2 Nanorods on Oxygen Functional Groups-Rich Sponge-Like Carbon Fibers.

This work addresses the challenges in developing carbon fiber paper-based supercapacitors (SCs) with high energy density by focusing on the limited capacity of carbon fiber. To overcome this limitation, a sponge-like porous carbon fiber paper enriched with oxygen functional groups (OFGs) is prepared, and Cu(OH)2 nanorods are grown on its surface to construct the SC anode. This design results in a multi-layered carbon fiber paper-based electrode with a specific structure and enhanced capacitance. The Cu(OH)2 @PCFP anode exhibits an areal capacitance of 547.83 mF cm-2 at a current density of 1 mA cm-2 and demonstrates excellent capacitance retention of 99.8% after 10 000 cycles. Theoretical calculations further confirm that the Cu(OH)2 /OFGs-graphite heterostructure exhibits higher conductivity, facilitating faster charge transfer. A solid-state SC is successfully assembled using Ketjen Black@PCFP as the cathode and KOH/PVA as the gel electrolyte. The resulting device exhibits an energy density of 0.21 Wh cm-2 at 1.50 mW cm-2 , surpassing the performance of reported Cu(OH)2 SCs. This approach, combining materials design with an understanding of underlying mechanisms, not only expands the range of electrode materials but also provides valuable insights for the development of high-capacity energy storage devices.

LncRNA MYLK antisense RNA 1 activates cell division cycle 42/Neutal Wiskott-Aldrich syndrome protein pathway via microRNA-101-5p to accelerate epithelial-to-mesenchymal transition of colon cancer cells.

Long noncoding RNA MYLK antisense RNA 1 (MYLK-AS1) is the crux in multiple diseases. Therefore, the purpose of this study was to investigate the possible mechanism of MYLK-AS1. A total of 62 colon cancer (CC) specimens and paired adjacent normal tissues were collected, and the expression of MYLK-AS1, microRNA (miR)-101-5p/cell division cycle 42 (CDC42) was detected. CC cell lines were transfected with MYLK-AS1, miR-101-5p, CDC42-related plasmids, and the biological functions and markers of epithelial-mesenchymal transition (EMT) were analyzed. The binding relationship between MYLK-AS1, miR-101-5p, and CDC42 was evaluated. In CC tissues and cell lines, MYLK-AS1 and CDC42 were highly expressed, and miR-101-5p was lowly expressed. Inhibition of MYLK-AS1 or upregulation of miR-101-5p can inhibit CC cell growth and EMT. miR-101-5p inhibited CDC42/N-wasp axis activation in CC cells by targeting CDC42. Knockdown of CDC42 or upregulation of miR-101-5p partially reversed the effects caused by upregulation of MYLK-AS1. MYLK-AS1, which is significantly upregulated in CC, may be a molecular sponge for miR-101-5p, and MYLK-AS1 promotes the activation of the CDC42/N-wasp axis in CC cells by targeting CDC42 through miR-101-5p, which in turn promotes tumor development. MYLK-AS1 may be a potential biomarker and target for CC therapy.

Hydrophobic Cross-Linked Chains Regulate High Wet Tissue Adhesion Hydrogel with Toughness, Anti-hydration for Dynamic Tissue Repair.

Hydrogel adhesion materials are widely reported for tissue engineering repair applications, however, wet tissue surface moisture can reduce the wet-adhesion properties and mechanical strength of hydrogels limiting their application. Here, anti-hydration gelatin-acrylic acid-ethylene dimethacrylate (GAE) hydrogels with hydrophobic cross-linked chains are constructed. The prepared GAE hydrogel is soaked in PBS (3 days) with a volume change of 0.6 times of the original and the adhesive strength, Young's modulus, toughness, and burst pressure are maintained by ≈70% of the original. A simple and universal method is used to introduce hydrophobic chains as cross-linking points to prepare hydrogels with anti-hydration, toughness, and high wet state adhesion. The hydrophobic cross-linked chains not only restrict the movement of molecular chains but also hinder the intrusion of water molecules. Antihydration GAE hydrogels exhibit good biocompatibility, slow drug release, and dynamic oral wet-state tissue repair properties. Therefore, the anti-hydration hydrogel has excellent toughness, wet tissue adhesion properties, and good prospects for biological applications.

Has the consistency evaluation policy of generic drugs promoted the innovation quality of Chinese pharmaceutical manufacturing industry? An empirical study based on the difference-in-differences model.

Introduction: In March 2016, the Chinese government officially launched a nationwide consistency evaluation of the quality and efficacy of generic drugs. Methods: This paper conducted an empirical study using the Difference-in-Differences method to explore the effect of this policy on the innovation quality of China's pharmaceutical manufacturing industry and further analyzed the underlying mechanism of action. Results: The results of the study show that the generic consistency evaluation policy has a significant promotion effect on the innovation quality of China's pharmaceutical manufacturing industry, and the promotion effect is the largest for non-state-owned enterprises and enterprises in the central region; in addition, the intensity of R&D capital investment and R&D personnel investment which play a mediating role. Discussion: Therefore, we should fully recognize the positive effect of generic drug consistency evaluation policy on improving the innovation quality of the pharmaceutical manufacturing industry and pay attention to the necessity of regional coordination and unification in policy implementation and the formulation of supporting policy tools. This study provides empirical evidence for the implementation effect of the generic drug consistency evaluation policy, which can provide an essential reference for the further improvement of the procedure and the R&D decision-making of pharmaceutical enterprises.

Life's Essential 8 and heart failure among patients with chronic kidney disease: the Kailuan Cohort Study.

AIMS: Patients with chronic kidney disease (CKD) are at an increased risk of developing heart failure. The American Heart Association recently released a new metric, Life's Essential 8 (LE8), for health promotion. However, evidence regarding associations between LE8 and heart failure risk among patients with CKD is scarce. METHODS: A total of 16,190 patients with CKD (mean age 55.9 years), free of cardiovascular disease at recruitment from the Kailuan study, were included. Cardiovascular health was assessed using the LE8 score. Incident heart failure events were ascertained via linkage of electronic health record data. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 814 (5.0%) patients in the high LE8 criteria, with 13,180 (81.4%) in the moderate, and 2,196 (13.6%) in the low LE8 category, respectively. During a median follow-up of 13.7 years, 724 incident heart failure cases were documented. Compared with the low LE8 category, the HRs (95% CIs) for heart failure were 0.58 (0.48, 0.71) for the moderate LE8 category, and 0.32 (0.19, 0.54) for the high LE8 category (P for trend <0.001). In addition, the association was stronger in patients aged ≤65 years compared with their older counterparts (P for interaction = 0.01). CONCLUSION: Our data showed a strong graded inverse association between the LE8-defined cardiovascular health and the risk of heart failure among patients with CKD. Our findings support the importance of adopting the LE8 among patients with CKD to prevent heart failure.

Using the Life's Essential 8 (LE8) score, released by the American Heart Association for cardiovascular health promotion, this study investigated the relationship between cardiovascular health and the risk of heart failure in patients with chronic kidney disease (CKD) in China. Patients with CKD who had better cardiovascular health, as indicated by higher LE8 scores, had a significantly lower risk of heart failure.A stronger association between better LE8 score and lower risk of heart failure among CKD patients aged ≤65 years was observed, compared with their older counterparts.

A segmentation model to detect cevical lesions based on machine learning of colposcopic images.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

MHC class II regulation of CD8+ T cell tolerance and implications in autoimmunity and cancer immunotherapy.

Major histocompatibility complex (MHC) class II-reactive CD8+ T cells are found in humans and animals, but little is known about their identity, development, and function. In this study, we discover a group of CD8+ T cells reactive to both MHC class I and II molecules in MHC class II-deficient mice. We clone their T cell receptors (TCRs) and analyze their development and function. In wild-type animals, thymocytes bearing those TCRs are purged by negative selection. In the absence of MHC class II, they develop into mature CD8+ T cells. When encountering MHC class II in the periphery, they undergo robust activation and proliferation, attack self-tissues, and cause lethal autoimmune diseases. In adoptive T cell therapy, those CD8+ T cells are able to efficiently control MHC class II-expressing tumors. This study opens the door to investigation of dual-reactive CD8+ T cells, their development and selection in the thymus, and the perils and promises when their normal development and selection are compromised.