Environmental pollution is a significant public health challenge worldwide, and investigating the causal relationship between environmental exposure and population health outcomes is a key objective of environmental epidemiology research. In recent years, the complexity of environmental exposures has increasingly come to the forefront, making it challenging for observational studies that dominate environmental epidemiology to accurately estimate causal effects. Causal inference methods are particularly advantageous in controlling for confounding factors, thus holding great potential in environmental epidemiology research. Researchers can use appropriate causal inference methods to simulate the process of randomization, providing strong support for revealing the causal relationship between environmental exposure and health outcomes. However, there is a lack of reviews on the application of causal inference methods in environmental epidemiology studies in China. Therefore, this study introduced the basic principles of common causal inference statistical methods in environmental epidemiology, summarized the applicable conditions, advantages and disadvantages of various methods, and provided R software implementation codes for these methods, aiming to offer guidance for optimizing research design and practicing causal inference statistical methods.

A portion of patients undergoing implant restoration require bone augmentation procedures to ensure that there is sufficient bone volume around the implant. For the patients with horizontal bone ridge defects at edentulous sites, with or without mild to moderate vertical bone defects, the shell technique serves as a reliable and minimally invasive bone augmentation method with effective space maintenance. The shell technique involves fixating 1 mm cortical bone blocks to the recipient site, using retention screws and filling the gap between the bone block and recipient bed with particulate bone substitute materials, and covering the barrier membrane to achieve bone augmentation. The overlying tension-free soft tissue closure seals the surgical site while local peripheral blood releases osteoclasts and cytokines that gradually degrade the bone block. The rigid fixation of the bone block ensures a stable internal environment for osteogenesis and a new bone regeneration cycle. Although this technique demonstrates favorable bone augmentation outcomes, it is highly technique-sensitive. There are certain differences in the application scenarios and osteogenic processes for autologous and allogeneic bone shells. The selection of bone blocks and particulate bone substitute materials significantly influences the osteogenic biological process and the predictability of bone augmentation results. Complications associated with the shell technique possess distinct characteristics, such as the immunogenicity of allogeneic bone fragments, soft tissue cracking, and bone fragment loosening. Their prevention and subsequent management substantially impact the success rate of osteogenesis. This article delves into the biological mechanisms of osteogenesis in the bone block technique, summarizing the indications, clinical outcomes, classification of bone blocks, and surgical workflow management, as well as complication prevention and management, aiming to provide a reference for the future application and development of the bone shell technique.

Wilson disease （WD） is a hereditary disorder of copper metabolism characterized by abnormal copper accumulation in tissues， including the liver and brain， which leads to severe hepatic and neurological damage. This disease is often accompanied by lipid metabolism abnormalities， and the exploration of related mechanisms has attracted increasing attention. This article introduces the clinical features of lipid metabolism disorders in WD patients， summarizes the research advances in the serum levels of lipids and hepatic steatosis， analyzes the potential mechanisms of the interaction between copper and lipid metabolism， and highlights the significance of lipid-related molecules in disease diagnosis and clinical evaluation. In clinical practice， the monitoring and assessment of lipid metabolism parameters should be taken seriously in patients with WD， in order to promote comprehensive disease management and improve the prognosis of patients.

Functional cure is currently the ideal treatment endpoint for chronic hepatitis B （CHB） in China and globally. HBsAg seroclearance and HBV DNA that cannot be detected in peripheral blood for more than 24 weeks marks the regression of hepatitis B virus （HBV） infection. However， there is still a lack of systematic description of the characteristics of intrahepatic HBV markers after HBsAg seroclearance. This article elaborates on the issues including the latest definition of functional cure， the characteristics of intrahepatic virological markers after HBsAg seroclearance， the significance of ultrasensitive serum HBsAg detection， and antiviral therapy for CHB patients with a low level of HBsAg， so as to improve the understanding of functional cure among clinicians.

BACKGROUND: Enzalutamide, a second-generation androgen receptor (AR) pathway inhibitor, is widely used in the treatment of castration-resistant prostate cancer. However, after a period of enzalutamide treatment, patients inevitably develop drug resistance. In this study, we characterized leucine-rich repeated G-protein-coupled receptor 5 (LGR5) and explored its potential therapeutic value in prostate cancer. METHODS: A total of 142 pairs of tumor and adjacent formalin-fixed paraf-fin-embedded tissue samples from patients with prostate cancer were collected from the Pathology Department at Sun Yat-sen Memorial Hos-pital. LGR5 was screened by sequencing data of enzalutamide-resistant cell lines combined with sequencing data of lesions with different Gleason scores from the same patients. The biological function of LGR5 and its effect on enzalutamide resistance were investigated in vitro and in vivo . Glutathione-S-transferase (GST) pull-down, coimmunoprecipitation, Western blotting, and immunofluorescence assays were used to explore the specific binding mechanism of LGR5 and related pathway changes. RESULTS: LGR5 was significantly upregulated in prostate cancer and negatively correlated with poor patient prognosis. Overexpression of LGR5 promoted the malignant progression of prostate cancer and reduced sensitivity to enzalutamide in vitro and in vivo . LGR5 promoted the phosphorylation of glycogen synthase kinase-3β (GSK-3β) by binding heat shock protein 90,000 alpha B1 (HSP90AB1) and mediated the activation of the Wingless/integrated (WNT)/β-catenin signaling pathway. The increased β-catenin in the cytoplasm entered the nucleus and bound to the nuclear AR, promoting the transcription level of AR, which led to the enhanced tolerance of prostate cancer to enzalutamide. Reducing HSP90AB1 binding to LGR5 significantly enhanced sensitivity to enzalutamide. CONCLUSIONS LGR5 directly binds to HSP90AB1 and mediates GSK-3β phosphorylation, promoting AR expression by regulating the WNT/β-catenin signaling pathway, thereby conferring resistance to enzalutamide treatment in prostate cancer.
Male ; Humans ; Phenylthiohydantoin/pharmacology* ; Benzamides ; Receptors, G-Protein-Coupled/genetics* ; Nitriles ; Cell Line, Tumor ; HSP90 Heat-Shock Proteins/metabolism* ; Drug Resistance, Neoplasm/genetics* ; Prostatic Neoplasms/drug therapy* ; beta Catenin/metabolism* ; Receptors, Androgen/genetics* ; Animals ; Mice ; Wnt Signaling Pathway/physiology*

Background: Developing and validating a modified parameter, the SYS-G angle (the angle between the lower endplate of the C2 and the upper endplate of C7 vertebrae), as a feasible substitute for the C2–C7 Cobb method in assessing cervical sagittal alignment and exploring its reference range through a large-scale retrospective study. Methods: The visibility of the C6, C7 upper, and C7 lower endplates was graded and compared. Baseline data such as height, weight, body mass index (BMI), age, and sex were analyzed for their impact on the visibility of the C7 lower endplate. Values of C2-6 Cobb angle, SYS-G angle, and C2-7 Cobb angle were measured. The intra- and interobserver reliability, differences, and efficacy of evaluation on cervical lordosis of the parameters were compared, and the correlations among the parameters were analyzed. Furthermore, reference ranges for the SYS-G angle were established based on lateral cervical spine x-rays of 825 asymptomatic Chinese adults across different age groups and sexes. Results: The visibility of the C7 lower endplates was significantly reduced compared to the C6 lower and C7 upper endplates.Age, weight, BMI, and male sex were identified as factors negatively influencing the visibility of the C7 lower endplate. Both intraobserver and interobserver reliability demonstrated excellence for all tested parameters. The linear regression model unveiled a stronger association of the SYS-G angle with the C2-7 Cobb angle compared to the C2-6 Cobb angle. Furthermore, the SYS-G angle exhibited excellent efficacy in evaluating cervical lordosis. Age displayed a positive correlation with the SYS-G angle, and across every age bracket from 20 to 69 years, men exhibited a higher mean SYS-G angle compared to women. Conclusions The visibility of the C7 lower endplate diminishes with increasing age, weight, BMI, and male sex. In cases where the C7 lower endplate is unclear, the SYS-G angle emerges as a reliable method for estimating cervical sagittal morphology. Reference ranges for the SYS-G angle were established across various age groups and sexes among asymptomatic Chinese adults, offering a valuable resource to guide therapeutic interventions for cervical spine disorders and deformities.

Objective: To investigate the clinical efficacy of oral microscope-assisted microflap periodontal bone grafting in treating class Ⅱ furcation involvement in mandibular molars, and to provide clinical evidence for its treatment in furcation involvement. Methods: This study was reviewed and approved by the institutional ethics committee, and informed consent was obtained from all patients. Sixty mandibular molars with class II furcation involvement caused by periodontitis were enrolled in a randomized controlled clinical study, utilizing a random number table method. Patients were categorized into a control group (n=30) and an experimental group (n=30) based on the surgical procedure employed. The control group underwent periodontal flap surgery with an internal oblique incision and vertical incision; this procedure was performed without the aid of a microscope. Conversely, the experimental group underwent micro flap periodontal bone grafting surgery without vertical incision; an oral microscope was used for this procedure. Both groups were analyzed 6 months after surgery, and postoperative gingival recession (GR), probing depth (PD), bleeding index (BI), vertical bone height increase (VBHI), pain level, and complications were recorded. Results: Both groups showed improvement in PD and BI after 6 months compared to preoperative levels: the control group had a preoperative PD of (7.33 ± 1.72 mm) and a 6-month postoperative PD of (3.37 ± 0.96 mm), with statistically significant differences (P<0.001). The preoperative PD of the experimental group was (7.27 ± 1.57 mm), and the 6-month postoperative PD was (3.00 ± 0.69 mm), with statistically significant differences (P<0.001). The BI of the control group decreased from 3.03 ± 1.03 before surgery to 0.77 ± 0.82 at 6 months after surgery (P<0.001), while the BI of the experimental group decreased from 3.20 ± 1.09 before surgery to 0.73 ± 0.64 at 6 months after surgery (P<0.001), and the differences were statistically significant. The experimental group showed a significant improvement in GR (0.70 ± 0.59 mm) compared to preoperative GR (1.26 ± 0.94 mm) at 6 months after surgery (P=0.007), while the control group showed an increase in GR (1.37 ± 0.89 mm) at 6 months after surgery compared to preoperative GR (1.13 ± 0.97 mm), but the difference was not statistically significant (P=0.337). The inter group comparison results showed that there were no statistically significant differences in PD and BI between the two groups at 6 months after surgery (PD: P=0.096, BI: P=0.861); The GR of the experimental group was lower than that of the control group, and the difference was statistically significant (P=0.001). There was no statistically significant difference in postoperative VBHI between the two groups (P=0.128). The pain level scores of the experimental group were lower than those of the control group at 4 and 24 hours after surgery (P<0.001). None of the patients experienced complications. Conclusion Microflap periodontal bone grafting assisted by an oral microscope effectively improves the periodontal condition of patients with grade Ⅱ root bifurcation lesions of mandibular molars, and the bone grafting effect is good, with mild pain and good safety.

During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People