OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

There are difficulties in the treatment of Alzheimer's disease (AD) in medical community. Since the surgery of cervical deep lymphatic vessel/lymphatic node-vein anastomosis (LVA/LnVA) has made clinical improvement in patients with AD, it offers a surgical option to treat AD. Especially improvements in cognitive impairment. However the mechanism in treatment of AD is not yet made clear. This article preliminarily explores the mechanism in improvement of some symptoms in patients with AD through cervical deep LVA/LnVA on the basis of morphological characteristics of the cribriform plate-cervical lymphatic pathway.

The interstitial protein UL14 of pseudorabies virus(PRV)constitutes a crucial compo-nent for viral replication and virulence invasion.It can interact with other viral proteins to complete the infection of the host,rendering it one of the potentially important antiviral targets.In this stud-y,the PRV DX strain isolated in the laboratory was used as the parental strain.The recombinant UL14 protein was expressed and purified through the prokaryotic expression system.BALB/c mice were immunized with this protein as an antigen.After three rounds of subcloning screening,three hybridoma cell lines against the UL14 protein were obtained,named 1B4,1B5,and 1F2,respective-ly.The immunoreactivity of the antibodies was detected by immunofluorescence assay(IFA).The results showed that the antibody titers of the 1B4 and 1B5 strains were not lower than 1∶3 200,and that of the 1F2 strain was not lower than 1∶2 000.The results of western blot(WB)detection showed that the antibody titers of the three strains were all not lower than 1∶8 000.The results of indirect ELISA detection showed that the antibody titers in ascites were all not lower than 112 800.The results of the identification of the antigenic epitopes of the UL14 protein showed that the antigenic epitope recognized by 1B4 was 1 MFASDRRERRVRLAEAFQRE20,and the antigenic epitopes recognized by 1B5 and 1F2 were speculated to be 33GRADKKNPEFVRAFMAAKQAR53.After PRV infected susceptible cells,the temporal expression of the UL14 protein was detected by IF A using the prepared monoclonal antibodies.It was found that the temporal expression of UL14 was similar to that of gC,and the result of RT-qPCR of UL14 gene was consistent with IF A,indi-cating that UL14 might be a late gene during the PRV replication.The subcellular localization of UL14 after virus infection was detected by IFA,and it was found that the UL14 protein could be transferred from the cytoplasm to the nucleus and the expression of UL14 protein increased with the extension of infection time.This study provides a good research tool for further investigating on the function of the PRV UL14 protein and might contribute to the further study of the PRV replication mechanism mediated by the PRV UL14 protein.

In 2025, coinciding with the 110th anniversary of the establishment of Chinese Medical Association, the authors systematically review the evolution of liver cancer research and liver surgery in China from its infancy to systematic development, and summarize the unremitting efforts and outstanding contributions made by the Chinese Medical Association in the field of liver cancer research in China, focusing on four technical dimensions: the update of surgical resection technology, breakthroughs in liver transplantation technology, the establishment of liver cancer transformation treatment paradigm, and the construction of Chinese characteristic liver cancer staging. With the elaborating on the development trajectory of the discipline in detail, and analysis of key historical nodes and major milestone events, the authors aim to provide historical insights for the prevention and treatment of liver cancer in China, and provide reference for future development directions.

The interstitial protein UL14 of pseudorabies virus(PRV)constitutes a crucial compo-nent for viral replication and virulence invasion.It can interact with other viral proteins to complete the infection of the host,rendering it one of the potentially important antiviral targets.In this stud-y,the PRV DX strain isolated in the laboratory was used as the parental strain.The recombinant UL14 protein was expressed and purified through the prokaryotic expression system.BALB/c mice were immunized with this protein as an antigen.After three rounds of subcloning screening,three hybridoma cell lines against the UL14 protein were obtained,named 1B4,1B5,and 1F2,respective-ly.The immunoreactivity of the antibodies was detected by immunofluorescence assay(IFA).The results showed that the antibody titers of the 1B4 and 1B5 strains were not lower than 1∶3 200,and that of the 1F2 strain was not lower than 1∶2 000.The results of western blot(WB)detection showed that the antibody titers of the three strains were all not lower than 1∶8 000.The results of indirect ELISA detection showed that the antibody titers in ascites were all not lower than 112 800.The results of the identification of the antigenic epitopes of the UL14 protein showed that the antigenic epitope recognized by 1B4 was 1 MFASDRRERRVRLAEAFQRE20,and the antigenic epitopes recognized by 1B5 and 1F2 were speculated to be 33GRADKKNPEFVRAFMAAKQAR53.After PRV infected susceptible cells,the temporal expression of the UL14 protein was detected by IF A using the prepared monoclonal antibodies.It was found that the temporal expression of UL14 was similar to that of gC,and the result of RT-qPCR of UL14 gene was consistent with IF A,indi-cating that UL14 might be a late gene during the PRV replication.The subcellular localization of UL14 after virus infection was detected by IFA,and it was found that the UL14 protein could be transferred from the cytoplasm to the nucleus and the expression of UL14 protein increased with the extension of infection time.This study provides a good research tool for further investigating on the function of the PRV UL14 protein and might contribute to the further study of the PRV replication mechanism mediated by the PRV UL14 protein.

In 2025, coinciding with the 110th anniversary of the establishment of Chinese Medical Association, the authors systematically review the evolution of liver cancer research and liver surgery in China from its infancy to systematic development, and summarize the unremitting efforts and outstanding contributions made by the Chinese Medical Association in the field of liver cancer research in China, focusing on four technical dimensions: the update of surgical resection technology, breakthroughs in liver transplantation technology, the establishment of liver cancer transformation treatment paradigm, and the construction of Chinese characteristic liver cancer staging. With the elaborating on the development trajectory of the discipline in detail, and analysis of key historical nodes and major milestone events, the authors aim to provide historical insights for the prevention and treatment of liver cancer in China, and provide reference for future development directions.

There are difficulties in the treatment of Alzheimer's disease (AD) in medical community. Since the surgery of cervical deep lymphatic vessel/lymphatic node-vein anastomosis (LVA/LnVA) has made clinical improvement in patients with AD, it offers a surgical option to treat AD. Especially improvements in cognitive impairment. However the mechanism in treatment of AD is not yet made clear. This article preliminarily explores the mechanism in improvement of some symptoms in patients with AD through cervical deep LVA/LnVA on the basis of morphological characteristics of the cribriform plate-cervical lymphatic pathway.

Objective:To explore the clinical effects of anterolateral femoral or anteromedial femoral perforator flaps in repairing skin and soft tissue defects after resection of cutaneous squamous cell carcinoma (CSCC).Methods:This study was a retrospective observational study. From July 2015 to July 2022, 21 patients with CSCC were treated in the Department of Burns and Plastic Surgery of Guizhou Provincial People's Hospital, including 15 males and 6 females, aged from 27 to 74 years. The area of skin and soft tissue defects after extended resection of CSCC was 7.5 cm×4.0 cm to 23.0 cm×8.5 cm. The wounds in 18 patients were repaired with anterolateral femoral perforator flaps; variations of perforating branch of the descending branch of lateral circumflex femoral artery were observed in 3 patients during the operation, and the wounds were repaired with anteromedial femoral perforator flaps. The flap areas were 8.0 cm×5.0 cm to 25.0 cm×10.0 cm. The wounds in the donor areas were sutured directly in 19 patients, and the wounds in the donor areas were repaired with thin and medium-thickness skin grafts in the contralateral thigh in 2 patients. The postoperative survival of flaps and the occurrence of vascular crisis were observed. The length of operation and the hospitalization day were recorded. The recurrence of tumor, the appearances of the donor and recipient areas of flaps, the function of the flap donor area were followed up. At the last follow-up, the satisfaction degree of patients for the curative effects was evaluated.Results:The flaps survived in 20 patients, while the vascular crisis occurred in 1 patient within 48 hours after operation, and the flap survived after immediate emergency operation. The length of operation was 4 to 5 hours, and the hospitalization day was 15 to 38 days. The patients were followed up for 1 to 6 years after operation, there was no local tumor recurrence, the color and texture of the flaps were with no obvious differences to those of the surrounding tissue, and the elasticity and appearance were good. The skin grafts in the flap donor areas of 2 patients survived well with local pigmentation. There was only linear scar in the flap donor areas of all patients, and there were no significant effects on sensory and motor functions. At the last follow-up, fifteen patients were satisfied with the curative effect, and 6 patients were generally satisfied with the curative effect.Conclusions:For skin and soft tissue defects after CSCC resection, the anterolateral femoral perforator flaps can be used preferentially. In the case of variation of the perforating branch of descending branch of the lateral circumflex femoral artery, the anteromedial femoral perforator flap is selected. The areas of the two flaps are large and can be adjusted according to the amount of defect tissue, thus accurately and effectively repairing skin and soft tissue defects after CSCC resection. The postoperative appearance and function are good.

The incidence of metabolic rheumatism gout has been increasing with a trend of more younger patients and atypical symptoms. Typical gout is easy to be diagnosed, but it is difficult for atypical cases. Finding uric acid crystal in articular fluid by polarizing light microscope is a gold standard of diagnosis, but it is an invasive diagnostic method and difficult to be widely used. The patients need further imaging examination for assistance of diagnosis and guide of follow-up treatment. This article reviews the research progress of different imaging methods used for diagnosis of gouty arthritis.

Objective To compare different drainage methods after right hepatectomy. Methods From April 2017 to February 2018, 90 patients who underwent right hepatectomy at Zhongshan Hospital of Fudan University were prospectively randomized to the latex tube group (right subphrenic drain with a latex tube connecting to a collection bag, n=30), the silicone tube group (right subphrenic drain with a silicone tube connecting to a closed-suction, n=30) or the combination group ( right subphrenic drain with a latex tub, combined with a silicone tube, n=30). The amount of fluid collection after the operation, complications after surgery, recovery of liver function, and length of hospital stay after operation were compared. Results There were no significant differences in the clinicopathological features among the 3 groups, including gender, age, cirrhosis status, extent of hepatectomy, and blood loss (P＞0. 05). There were no significant differences among the three groups on the incidences of postoperative complications [ the latex tube group, 20. 0% (6/30); the silicone tube group, 23. 3% (7/30); the combination group, 16. 7% (5/30); P＞0. 05]. Ultrasonography showed significantly lower rates of subphrenic collection in the combination group compared with the latex tube group and the silicone tube group [16. 7% (5/30) vs. 63. 3% (19/30) vs. 53. 3% (16/30); P＜0. 05]. The rates of postoperative fever, serum total bilirubin, ALT and postoperative hospital stay were similar among the three groups (P＞0. 05). Conclusions Drainage using the combina-tion of a latex tube connecting to a collection bag and a silicone tube connecting to closed-suction after right hepatectomy significantly reduced postoperatively subphrenic collection and prevented infection of the collec-tion. However, the treatment strategy did not delay liver function recovery, prolong hospital stay nor increase post-operative infection rate.