Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

ICG-labeled PD-L1-antagonistic affibody dimer for tumor imaging and enhancement of tumor photothermal-immunotherapy.

In clinical practice, tumor-targeting diagnosis and immunotherapy against programmed death ligand 1 (PD-L1) have a significant impact. In this research, a PD-L1-antagonistic affibody dimer (ZPD-L1) was successfully prepared through Escherichia coli expression system, and conjugated with the photosensitizer of ICG via N-hydroxysuccinimide (NHS) ester to develop a novel tumor-targeting agent (ICG-ZPD-L1) for both tumor imaging diagnosis and photothermal-immunotherapy simultaneously. In vitro, ZPD-L1 could specifically bind to PD-L1-positive LLC and MC38 tumor cells, and ICG-ZPD-L1-mediated photothermal therapy (PTT) also showed excellent phototoxicity to these tumor cells. In vivo, ICG-ZPD-L1 selectively enriched into the PD-L1-positive MC38 tumor tissues, and the high-contrast optical imaging of tumors was obtained. ICG-ZPD-L1-mediated PTT exhibited a potent anti-tumor effect in vivo due to its remarkable photothermal properties. Furthermore, ICG-ZPD-L1-mediated PTT significantly induced the immunogenic cell death (ICD) of primary tumors, promoted maturation of dendritic cells (DCs), up-regulated anti-tumor immune response, enhanced immunotherapy, and superiorly inhibited the growth of metastatic tumors. In addition, ICG-ZPD-L1 showed favorable biosafety throughout the brief duration of treatment. In summary, these results suggest that ICG-ZPD-L1 is a multifunctional tumor-targeting drug integrating tumor imaging diagnosis and photothermal-immunotherapy, and has great guiding significance for the diagnosis and treatment of clinical PD-L1-positive tumor patients.

Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review.

The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

Great genetic diversity of vector-borne bacteria and protozoan in wild rodents from Guangxi, China.

BACKGROUND: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. METHODS: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. RESULTS: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. CONCLUSIONS: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors.

Supramolecular Hydrogel Dexamethasone-Diclofenac for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) severely affects patients' quality of life and is commonly treated with glucocorticosteroids injections, like dexamethasone, which may have side effects. This study aimed to create a novel low dose of twin-drug hydrogel containing dexamethasone and diclofenac and explore its potential as a drug delivery system for an enhanced anti-inflammatory effect. Its characterization involved rheology, transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Furthermore, the hydrogel demonstrated thixotropic properties. The hydrogel exhibited no cytotoxicity against RAW 264.7 macrophages. Furthermore, the hydrogel demonstrated a significant anti-inflammatory efficacy by effectively downregulating the levels of NO, TNF-α, and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The co-delivery approach, when intra-articularly injected in adjuvant-induced arthritis (AIA) rats, significantly alleviated chronic inflammation leading to reduced synovitis, delayed bone erosion onset, and the downregulation of inflammatory cytokines. The biocompatibility and adverse effect evaluation indicated good biological safety. Furthermore, the hydrogel demonstrated efficacy in reducing NF-κB nuclear translocation in LPS-induced RAW 264.7 macrophages and inhibited p-NF-kB, COX-2, and iNOS expression both in RAW 264.7 macrophages and the joints of AIA rats. In conclusion, the findings indicate that the hydrogel possesses potent anti-inflammatory activity, which effectively addresses the limitations associated with free forms. It presents a promising therapeutic strategy for the management of RA.

Single-cell analysis identifies critical regulators of spermatogonial development and differentiation in cattle-yak bulls.

Spermatogenesis is a continuous process in which functional sperm are produced through a series of mitotic and meiotic divisions and morphological changes in germ cells. The aberrant development and fate transitions of spermatogenic cells cause hybrid sterility in mammals. Cattle-yak, a hybrid animal between taurine cattle (Bos taurus) and yak (Bos grunniens), exhibits male-specific sterility due to spermatogenic failure. In the present study, we performed single-cell RNA sequencing analysis to identify differences in testicular cell composition and the developmental trajectory of spermatogenic cells between yak and cattle-yak. The composition and molecular signatures of spermatogonial subtypes were dramatically different between these 2 animals, and the expression of genes associated with stem cell maintenance, cell differentiation and meiotic entry was altered in cattle-yak, indicating the impairment of undifferentiated spermatogonial fate decisions. Cell communication analysis revealed that signaling within different spermatogenic cell subpopulations was weakened, and progenitor spermatogonia were unable or delayed receiving and sending signals for transformation to the next stage in cattle-yak. Simultaneously, the communication between niche cells and germ cells was also abnormal. Collectively, we obtained the expression profiles of transcriptome signatures of different germ cells and testicular somatic cell populations at the single-cell level and identified critical regulators of spermatogonial differentiation and meiosis in yak and sterile cattle-yak. The findings of this study shed light on the genetic mechanisms that lead to hybrid sterility and speciation in bovid species.

Association of Serum Macrophage Migration Inhibitory Factor with 3-Month Poor Outcome and Malignant Cerebral Edema in Patients with Large Hemispheric Infarction.

BACKGROUND: We aimed to investigate the associations of macrophage migration inhibitory factor (MIF), toll-like receptors 2 and 4 (TLR2/4), and matrix metalloproteinase 9 (MMP9) with 3-month poor outcome, death, and malignant cerebral edema (MCE) in patients with large hemispheric infarction (LHI). METHODS: Patients with LHI within 24 h of onset were enrolled consecutively. Serum MIF, TLR2/4, and MMP9 concentrations on admission were measured. Poor outcome was defined as a modified Rankin Scale score of ≥ 3 at 3 months. MCE was defined as a decreased level of consciousness, anisocoria and midline shift > 5 mm or basal cistern effacement, or indications for decompressive craniectomy during hospitalization. The cutoff values for MIF/MMP9 were obtained from the receiver operating characteristic curve. RESULTS: Of the 130 patients with LHI enrolled, 90 patients (69.2%) had 3-month poor outcome, and MCE occurred in 55 patients (42.3%). Patients with serum MIF concentrations ≤ 7.82 ng/mL for predicting 3-month poor outcome [adjusted odds ratio (OR) 2.827, 95% confidence interval (CI) 1.144-6.990, p = 0.024] also distinguished death (adjusted OR 4.329, 95% CI 1.841-10.178, p = 0.001). Similarly, MMP9 concentrations ≤ 46.56 ng/mL for predicting 3-month poor outcome (adjusted OR 2.814, 95% CI 1.236-6.406, p = 0.014) also distinguished 3-month death (adjusted OR 3.845, 95% CI 1.534-9.637, p = 0.004). CONCLUSIONS: Lower serum MIF and MMP9 concentrations at an early stage were independently associated with 3-month poor outcomes and death in patients with LHI. These findings need further confirmation in larger sample studies.

RNA Interference-Mediated Suppression of Ecdysone Signaling Inhibits Choriogenesis in Two Coleoptera Species.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the effect of chemical components on eggshell deserve further exploration. In two representative coleopterans, a coccinellid Henosepilachna vigintioctopunctata and a chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and reduced CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two coleopteran species. Moreover, our findings suggest the deposition of a CLS on the chorions.

Anaplasma, Bartonella, and Rickettsia infections in Daurian ground squirrels (Spermophilus dauricus), Hebei, China.

Rodents have been confirmed as hosts of various vector-borne zoonotic pathogens and are important for the maintenance of these microbes in nature. However, surveillance for zoonotic pathogens is limited for many wild rodent species in China, so our knowledge of pathogen ecology, genetic diversity, and the risk of cross-species transmission to humans is limited. In this study, 165 spleen samples of Daurian ground squirrels (Spermophilus dauricus) were collected from Weichang Manchu and the Mongolian Autonomous County of Hebei Province, China, and Rickettsia, Bartonella, and Anaplasma were identified by DNA detection using polymerase chain reaction (PCR). Sequence analysis identified eight bacterial pathogens: R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, B. grahamii, B. jaculi, A. capra, and Candidatus Anaplasma cinensis. Co-infection of B. grahamii and R. raoultii in one sample was observed. Our results demonstrated the genetic diversity of bacteria in Daurian ground squirrels and contributed to the distribution of these pathogens. Six species, A. capra, R. raoultii, R. sibirica, Candidatus R. longicornii, B. washoensis, and B. grahamii, are known to be pathogenic to humans, indicating a potential public health risk to the local human population, especially to herders who frequently have close contact with Daurian ground squirrels and are thus exposed to their ectoparasites.

Crucial roles of specialized chitinases in elytral and hindwing cuticles construction in Leptinotarsa decemlineata.

BACKGROUND: The Colorado potato beetle (CPB), Leptinotarsa decemlineata, is a major potato (Solanum tuberosum) pest, infesting over 16 million km2 and causing substantial economic losses. The insect cuticle forms an apical extracellular matrix (ECM) envelope covering exposed organs to direct morphogenesis and confer structural protection. While select chitinase (Cht) genes have proven essential for larval development, their potential activities directing ECM remodeling underlying adult wing maturation remain undefined. RESULTS: We investigated the expression patterns and performed an oral RNA interference (RNAi) screen targeting 19 LdChts in late-instar L. decemlineata larvae. Subsequently, we assessed their effects on adult eclosion and wing characteristics. Knockdown of LdCht5, LdCht7, LdCht10, LdIDGF2, and LdIDGF4, as well as others from Group IV (LdCht15, LdCht12, LdCht17, and LdCht13) and Groups VII-X (LdCht2, LdCht11, LdCht1, and LdCht3), resulting in shrunken, misshapen elytra with reduced areal density, as well as transverse wrinkling and impaired wing-tip folding in hindwings. Scanning electron micrographs revealed eroded elytral ridges alongside thinned, ruptured hindwing veins, indicative of mechanical fragility post-LdCht suppression. Spectroscopic analysis uncovered biomolecular alterations underlying the elytral anomalies, including decreases in peaks representing chitin, proteins, and lipids. This loss of essential ECM components provides evidence for the fragility, wrinkling, and shrinkage observed in the RNAi groups. CONCLUSION: Our findings elucidate the crucial role of chitinases in the turnover of chitinous cuticles on beetle wings, offering insights into RNAi-based control strategies against this invasive pest. © 2024 Society of Chemical Industry.

Contrast-enhanced ultrasound for the preoperative prediction of pathological characteristics in breast cancer.

Objective: We aimed to investigate the value of contrast-enhanced ultrasound (CEUS) in the preoperative prediction of the histological grades and molecular subtypes of breast cancer. Methods: A total of 183 patients with pathologically confirmed breast cancer were included. Contrast enhancement patterns and quantitative parameters were compared in different groups. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of CEUS in the preoperative prediction of pathological characteristics, including histologic grade and molecular subtypes. Results: Heterogeneous enhancement, perfusion defects, and peripheral radial vessels were mostly observed in higher histologic grade (grade III) breast cancer. Heterogeneous enhancement and perfusion defect were the most effective indicators for grade III breast cancer, with the areas under the ROC curve of 0.768 and 0.756, respectively. There were significant differences in the enhancement intensity, post-enhanced margin, perfusion defects, and peripheral radial vessel among the different molecular subtypes of breast cancer (all P < 0.01). Perfusion defects and clear edge after enhancement were the best qualitative criteria for the diagnosis of HER-2 overexpressed and triple-negative breast cancers, and the corresponding areas under the ROC curves were 0.804 and 0.905, respectively. There were significant differences in PE, WiR, WiPI, and WiWoAUC between grade III vs grade I and II breast cancer (P < 0.05). PE, WiR, WiPI, and WiWoAUC had good efficiency in the diagnosis of high-histologic-grade breast cancer. PE had the highest diagnostic efficiency in Luminal A, while WiPI had the highest diagnostic efficiency in Luminal B subtype breast cancer, and the areas under the ROC curve were 0.825 and 0.838, respectively. WiWoAUC and WiR were the most accurate parameters for assessing triple-negative subtype breast cancers, and the areas under the curve were 0.932 and 0.922, respectively. Conclusion: Qualitative and quantitative perfusion analysis of contrast-enhanced ultrasound may be useful in the non-invasive prediction of the histological grade and molecular subtypes of breast cancers.

Genetic diversity of vector-borne zoonotic pathogens in companion dogs and cats, Tianjin, China.

Background: Dogs and cats are the hosts of many vector-borne human pathogens that can be transmitted to humans. Given their direct and intimate contact with humans, companion dogs and cats are considered direct sentinels of vector-borne human pathogens. However, limited information is currently available regarding canine and feline zoonotic pathogens in China. This study detected canine and feline vector-borne human pathogens to better understand the potential risk to humans. Methods: Blood samples were collected from 275 domestic companion animals (117 dogs and 158 cats) living in Tianjin city, China, and the presence of DNA from Anaplasma, Babesia, Bartonella, and Rickettsia was detected by semi-nested polymerase chain reaction (PCR). The PCR products of the expected size were sequenced, and these newly generated sequences were subjected to BLASTN, nucleotide identity, and phylogenetic analyses. Results: A total of 24 blood samples tested positive for vector-borne pathogens in companion dogs and cats in Tianjin city, China, with a relatively low positive rate of 8.7%. Specifically, seven human pathogens, including Rickettsia raoultii, Candidatus Rickettsia jingxinensis, Rickettsia sibirica, Rickettsia felis, Babesia venatorum, Bartonella tribocorum, and Bartonella Henselae, were identified. In addition, Anaplasma ovis with zoonotic potential and Candidatus A. cinensis were detected. Conclusion: Our results indicate substantial genetic diversity in the vector-borne human pathogens circulating in companion dogs and cats. Interventions based on "One Health" should be taken to reduce the potential risks of contracting infection from companion dogs and cats in Tianjin, China.

Genome editing of FTR42 improves zebrafish survival against virus infection by enhancing IFN immunity.

The development of CRISPR-Cas9 technology introduces an efficient tool for precise engineering of fish genomes. With a short reproduction cycle, zebrafish infection mode can be referenced as antiviral breeding researches in aquaculture fish. Previously we identified a crucian carp-specific gene ftrca1 as an inhibitor of interferon response in vitro. Here, we demonstrate that genome editing of zebrafish ftr42, a homolog of ftrca1, generates a zebrafish mutant (ftr42lof/lof) with an improved resistance to SVCV infection. Zebrafish ftr42 acts as a virus-induced E3 ligase and downregulates IFN antiviral response by facilitating TBK1 protein degradation and also IRF7 mRNA decay. Genome editing results in loss of function of zebrafish ftr42, which enables zebrafish to have enhanced interferon response, thus improving zebrafish survival against virus infection. Our results suggest that fine-tuning fish IFN innate immunity through genome editing of negative regulators can genetically improve viral resistance in fish.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

Research trends on traditional Chinese medicine and acute pancreatitis: A bibliometric analysis from 2007 to mid-2023.

Traditional Chinese Medicine (TCM) is a unique medical system of historic significance, holding substantial influence within China and beyond. In recent years, the efficacy of TCM in treating acute pancreatitis has been substantiated. Despite over two decades of development in this domain, a bibliometric analysis illustrating TCM's role in acute pancreatitis remains scarce. OBJECTIVE: This study aims to conduct a comprehensive analysis of findings in the field of acute pancreatitis and TCM using machine learning and text-analyzing methodologies. The intent is to provide scientific and intuitive support to researchers and clinicians. METHODS: We searched the Web of Science Core Collection database for publications and related literature from 2007 to mid-2023. Tools such as Excel, Citespace V, and Vosviewer were utilized for bibliometric analysis. That included assessing published and cited counts, co-authorship mapping, co-citation analysis, burst detection, and keyword analysis. RESULTS: The study revealed a fluctuating growth trend in the number of publications and citations since 2007. As many as 147 institutions from 13 countries, with a total of 756 authors, have published 202 papers in 76 academic journals. Sichuan University in China and Tang Wenfu have been recognized as the most influential national institution and author. The most frequently published journal is "Pancreas", while the most cited is the "World Journal of Gastroenterology". Commonly used single herbs in this field include Baicalin, Emodin, Rhubarb, and Salvia miltiorrhizae. Frequently used herbal formulations include Da chengqi decoction, Chaiqin chengqi decoction, and Qing yi decoction. Current research hotspots primarily surround concepts like hmgb1, nf-kappab, nfr2, oxidative stress, exosomes, nlrp3, pyroptosis, etc. Potential future research themes could relate to pharmacology, reducing hmgb1, inflammatory response, cell activation, Qing Yi-decoction, etc. This review holds significant guiding importance for clinical and scientific research into TCM treatment for acute pancreatitis in the future.

Two new species of Hypodontolaiminae (Nematoda, Chromadorida, Chromadoridae) from the Yellow Sea with a phylogenetic analysis in the subfamily.

Two new species of Hypodontolaiminae, Dichromadoramediasp. nov. and Neochromadoraparabilineatasp. nov., were isolated and described from the Yellow Sea, China. Dichromadoramediasp. nov. is characterized by four long cephalic setae, the amphidial fovea transverse oval in the male and slit-shaped in the female, the pharynx with a single posterior bulb, spicules curved and distally bifurcated, gubernaculum jointed, four (1+3) precloacal supplements papilliform, and the tail conical elongated with a short spinneret. Neochromadoraparabilineatasp. nov. is characterized by the buccal cavity with one large hollow dorsal tooth and two small subventral teeth, the pharynx with an obvious posterior bulb, spicules L-shaped and widened medially, gubernaculum boat-shaped, seven cup-shaped and equidistant precloacal supplements, and a long and gradually tapering tail. The phylogenetic analysis of maximum likelihood and Bayesian inference based on rDNA sequences confirmed the taxonomic positions of Neochromadoraparabilineatasp. nov. and Dichromadoramediasp. nov. within Hypodontolaiminae. Tree topology in Hypodontolaiminae shows the genera Neochromadora, Dichromadora, Ptycholaimellus, and Spilophorella as polyphyletic groups, and the genus Chromadorita as a paraphyletic group.

Lei's formula attenuates osteoarthritis mediated by suppression of chondrocyte senescence via the mTOR axis: in vitro and in vivo experiments.

Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Existing research has shed light on the role of the mTOR signaling pathway in promoting chondrocyte senescence, a central factor in OA-related cartilage degeneration. Consequently, targeting mTOR to mitigate chondrocyte senescence presents a promising avenue for OA treatment. The primary objective of this study is to establish LSF's chondroprotective potential and confirm its anti-osteoarthritic efficacy through mTOR inhibition. In vivo assessments using an OA mouse model reveal substantial articular cartilage degeneration. However, LSF serves as an effective guardian of articular cartilage, evidenced by reduced subchondral osteosclerosis, increased cartilage thickness, improved surface smoothness, decreased OARSI scores, elevated expression of cartilage anabolic markers (Col2 and Aggrecan), reduced expression of catabolic markers (Adamts5 and MMP13), increased expression of the chondrocyte hypertrophy marker (Col10), and decreased expression of chondrocyte senescence markers (P16 and P21). In vitro findings demonstrate that LSF shields chondrocytes from H2O2-induced apoptosis, inhibits senescence, enhances chondrocyte differentiation, promotes the synthesis of type II collagen and proteoglycans, and reduces cartilage degradation. Mechanistically, LSF suppresses chondrocyte senescence through the mTOR axis, orchestrating the equilibrium between chondrocyte anabolism and catabolism, ultimately leading to reduced apoptosis and decelerated OA cartilage degradation. LSF holds significant promise as a therapeutic approach for OA treatment, offering new insights into potential treatments for this prevalent age-related condition.

Follow-up Value of Hip Medial Ultrasound in Infants and Children With Developmental Dysplasia of the Hip Treated With Reduction and Spica Casting.

OBJECTIVE: Closed or open reduction and spica casting are common treatments for children aged 6 to 18 months, as well as infants aged 0 to 6 months whose harness treatment for developmental dysplasia of the hip (DDH) was unsuccessful. The study aimed to quantify the distance between the femoral head and the acetabulum after closed or open reduction and evaluate the dynamic docking progression of the femoral head using serial hip medical ultrasound. METHODS: We retrospectively reviewed the medical records and hip medial ultrasound images of a consecutive series of patients with DDH who underwent spica casting after reduction and compared images obtained immediately after reduction and at follow-up. The first cast (stage I) was maintained for 2 to 3 months and scheduled for outpatient repeat ultrasound in 4 to 8 weeks. Then the second cast was placed (stage II), lasting for another 2 to 3 months. The triradiate cartilage-femoral head distance (TFD) was measured in the acetabulum coronal mid-sectional plane. The Wilcoxon signed-rank test was used to compare the TFD values. RESULTS: This study included 49 patients. All patients underwent hip medial ultrasound 0 to 3 days after stage I (time 1) and 4 to 8 weeks (time 2) postoperatively, with 24 patients reviewed again 0 to 7 days after stage II. The TFD values in time 1 and time 2 were 6.0 (5.0, 9.0) mm and 5.0 (3.6, 7.0) mm, respectively. There was a statistically significant difference between times 1 and 2 regarding TFD values in 49 close-reduction hips (6.0 vs 5.0 mm, P < 0.001). Similar findings were also observed in 13 open-reduction hips (6.0 vs 5.0 mm, P = 0.023). CONCLUSIONS: Hip medial ultrasonography during the period of cast immobilization after reduction in children with DDH can objectively and quantitatively show the dynamic change of the distance between the femoral head and the acetabulum, and can be used to assess reduction of the hip and progression of femoral head docking. LEVEL OF EVIDENCE: Level II-prognostic study.