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

Objective:To summarize the treatment experience of diabetes mellitus combined with necrotizing fasciitis.Methods:A retrospective analysis was conducted on the clinical data of patients diagnosed with diabetes mellitus and necrotizing fasciitis who were admitted to the Department of Burns and Plastic Surgery, Affiliated Hospital of Guizhou Medical University between September 2018 and December 2020. Upon admission, initial treatment involved blood glucose management, the administration of empirical antibiotics to combat infection, and concurrent nutritional support therapy. Surgical interventions, including either dilatation or incision and drainage, were promptly performed within 24 to 72 hours. During these procedures, necrotic tissues and purulent exudates were collected for pathogen culture and antibiotic sensitivity testing to guide appropriate treatment. Post-operatively, a negative pressure closed drainage system was installed to facilitate wound drainage, combined with 1.5% hydrogen peroxide solution to flush the wound or subcutaneous placement of multiple drainage tubes to drain the wound. If post-surgical infection persisted, additional dilatations were deemed necessary. Under the condition of clean wound and fresh granulation tissue, the wound was repaired by medium-thickness skin grafting on the lateral thigh. The laboratory risk indicator for necrotizing fasciitis (LRINEC) was checked and scored, including C-reactive protein, white blood cell count, hemoglobin, blood sodium, blood creatinine, and blood glucose levels. The total score was 0-13 points. When the score was ≥ 6 points, necrotizing fasciitis should be actively suspected. Observation of trauma infection control, statistics on the number of dilatations, trauma repair modalities, hospitalization time, and amputations, and follow-up of trauma healing and recurrence of necrotizing fasciitis were recorded.Results:A total of nine patients were enrolled, consisting of seven males and two females, with an age range of 39 to 81 years. The study population comprised patients with diabetes mellitus, with durations ranging from 0.5 to 10 years. The affected body parts included one upper extremity, six lower extremities, one perineum, and one case involving both a perineum and a lower extremity. LRINEC score ≥ 8 points in 5 cases and 6-7 points in 4 cases. The wound infection was controlled after 1 time dilatations in 4 cases, 2 times in 3 cases and 3 times in 2 cases, the infection of the trauma was controlled and reached a clean and fresh state of granulation tissue.In 7 cases, the trauma was healed after repairing with thick-medium-thick dermal grafting; in 1 case, the trauma was repaired by thin-medium-thick dermal grafting with scattered punctate recurring oozing, which was healed after changing the medication; and in 1 case, the right middle calf leg was amputated. Microbiological culture result: 2 cases of Staphylococcus aureus treated with intravenous drip of ceftazidime 2 000 mg once a day; 1 case of Pseudomonas pseudomallei was treated with intravenous drip of fluconazole 400 mg once a day; 2 cases of Enterococcus faecalis and 2 cases of Enterococcus faecium treated with intravenous drip of piperacillin and tazobactam sodium 4 500 mg 3 times a day, 2 cases of Escherichia coli treated with intravenous drip of levofloxacin 500 mg once a day. The duration of hospitalization of 9 patients ranged from 24 to 56 days. At discharge, LRINEC was significantly improved compared with admission, and LRINEC score was 0-2 points. Follow-up ranged from 3 months to 2 years, relapsed infection happended in the affected limb wound in one case, which healed after anti-infection and dressing change. The other cases healed well without recurrence. Conclusion:In the management of diabetic necrotizing fasciitis, concurrent comprehensive glycemic control and surgical intervention are crucial. The integration of vacuum sealing drainage and the employment of 1.5% hydrogen peroxide for wound cleansing, along with a consistent and prolonged antibiotics reatment course significantly contributes to improved disease control, promote wound healing, leading to reduced mortality and lower rates of amputation.

Objective:To summarize the treatment experience of diabetes mellitus combined with necrotizing fasciitis.Methods:A retrospective analysis was conducted on the clinical data of patients diagnosed with diabetes mellitus and necrotizing fasciitis who were admitted to the Department of Burns and Plastic Surgery, Affiliated Hospital of Guizhou Medical University between September 2018 and December 2020. Upon admission, initial treatment involved blood glucose management, the administration of empirical antibiotics to combat infection, and concurrent nutritional support therapy. Surgical interventions, including either dilatation or incision and drainage, were promptly performed within 24 to 72 hours. During these procedures, necrotic tissues and purulent exudates were collected for pathogen culture and antibiotic sensitivity testing to guide appropriate treatment. Post-operatively, a negative pressure closed drainage system was installed to facilitate wound drainage, combined with 1.5% hydrogen peroxide solution to flush the wound or subcutaneous placement of multiple drainage tubes to drain the wound. If post-surgical infection persisted, additional dilatations were deemed necessary. Under the condition of clean wound and fresh granulation tissue, the wound was repaired by medium-thickness skin grafting on the lateral thigh. The laboratory risk indicator for necrotizing fasciitis (LRINEC) was checked and scored, including C-reactive protein, white blood cell count, hemoglobin, blood sodium, blood creatinine, and blood glucose levels. The total score was 0-13 points. When the score was ≥ 6 points, necrotizing fasciitis should be actively suspected. Observation of trauma infection control, statistics on the number of dilatations, trauma repair modalities, hospitalization time, and amputations, and follow-up of trauma healing and recurrence of necrotizing fasciitis were recorded.Results:A total of nine patients were enrolled, consisting of seven males and two females, with an age range of 39 to 81 years. The study population comprised patients with diabetes mellitus, with durations ranging from 0.5 to 10 years. The affected body parts included one upper extremity, six lower extremities, one perineum, and one case involving both a perineum and a lower extremity. LRINEC score ≥ 8 points in 5 cases and 6-7 points in 4 cases. The wound infection was controlled after 1 time dilatations in 4 cases, 2 times in 3 cases and 3 times in 2 cases, the infection of the trauma was controlled and reached a clean and fresh state of granulation tissue.In 7 cases, the trauma was healed after repairing with thick-medium-thick dermal grafting; in 1 case, the trauma was repaired by thin-medium-thick dermal grafting with scattered punctate recurring oozing, which was healed after changing the medication; and in 1 case, the right middle calf leg was amputated. Microbiological culture result: 2 cases of Staphylococcus aureus treated with intravenous drip of ceftazidime 2 000 mg once a day; 1 case of Pseudomonas pseudomallei was treated with intravenous drip of fluconazole 400 mg once a day; 2 cases of Enterococcus faecalis and 2 cases of Enterococcus faecium treated with intravenous drip of piperacillin and tazobactam sodium 4 500 mg 3 times a day, 2 cases of Escherichia coli treated with intravenous drip of levofloxacin 500 mg once a day. The duration of hospitalization of 9 patients ranged from 24 to 56 days. At discharge, LRINEC was significantly improved compared with admission, and LRINEC score was 0-2 points. Follow-up ranged from 3 months to 2 years, relapsed infection happended in the affected limb wound in one case, which healed after anti-infection and dressing change. The other cases healed well without recurrence. Conclusion:In the management of diabetic necrotizing fasciitis, concurrent comprehensive glycemic control and surgical intervention are crucial. The integration of vacuum sealing drainage and the employment of 1.5% hydrogen peroxide for wound cleansing, along with a consistent and prolonged antibiotics reatment course significantly contributes to improved disease control, promote wound healing, leading to reduced mortality and lower rates of amputation.

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.

Objective:To observe the effect of vacuum sealing drainage(VSD)combined with hydrogen peroxide irrigation in the treatment of venous leg ulcer (VLU).Methods:The clinical data was focused on the cases with venous leg ulcer, who were treated by the Department of Plastic and Burn Surgery, Affiliated Hospital of Guizhou Medical University from January 2014 to March 2021. According to the treatment method, patients were divided into two groups. After debridement, the intervention group was irrigated with VSD combined with hydrogen peroxide, while the control group was irrigated with VSD combined with normal saline . The duration of VSD treatment was recorded, and the effective rate of wound treatment was calculated. According to the treatment situation, the medium thickness skin graft was performed, and the good survival rate of skin graft was calculated.Results:A total of 55 patients were enrolled in this study. Aged 35 to 86 years old, including 32 males and 23 females. Before the procedure, all the above patients underwent pathological examination to exclude the ulcers caused by malignant tumors. There were 34 cases in the intervention group and 21 cases in the control group. The duration of VSD treatment in the intervention group was (8.53±1.52) d, and that in the control group was (10.33±3.25) d, and the difference was statistically significant ( t=2.39, P=0.025). The effective rate of wound assessment was 82.35% (28/34) in the intervention group and 57.14% (12/21) in the control group; the difference was statistically significant ( χ2=4.16, P=0.041). The good survival rate of skin graft was 91.18% (31/34) in the intervention group and 61.90% (13/21) in the control group; the difference was statistically significant ( χ2=5.24, P=0.022). Conclusions:VSD combined with hydrogen peroxide irrigation is an effective method to treat VLU, which can shorten the preparation time of wounds and improve the survival rate of skin grafts.

Objective:To observe the effect of vacuum sealing drainage(VSD)combined with hydrogen peroxide irrigation in the treatment of venous leg ulcer (VLU).Methods:The clinical data was focused on the cases with venous leg ulcer, who were treated by the Department of Plastic and Burn Surgery, Affiliated Hospital of Guizhou Medical University from January 2014 to March 2021. According to the treatment method, patients were divided into two groups. After debridement, the intervention group was irrigated with VSD combined with hydrogen peroxide, while the control group was irrigated with VSD combined with normal saline . The duration of VSD treatment was recorded, and the effective rate of wound treatment was calculated. According to the treatment situation, the medium thickness skin graft was performed, and the good survival rate of skin graft was calculated.Results:A total of 55 patients were enrolled in this study. Aged 35 to 86 years old, including 32 males and 23 females. Before the procedure, all the above patients underwent pathological examination to exclude the ulcers caused by malignant tumors. There were 34 cases in the intervention group and 21 cases in the control group. The duration of VSD treatment in the intervention group was (8.53±1.52) d, and that in the control group was (10.33±3.25) d, and the difference was statistically significant ( t=2.39, P=0.025). The effective rate of wound assessment was 82.35% (28/34) in the intervention group and 57.14% (12/21) in the control group; the difference was statistically significant ( χ2=4.16, P=0.041). The good survival rate of skin graft was 91.18% (31/34) in the intervention group and 61.90% (13/21) in the control group; the difference was statistically significant ( χ2=5.24, P=0.022). Conclusions:VSD combined with hydrogen peroxide irrigation is an effective method to treat VLU, which can shorten the preparation time of wounds and improve the survival rate of skin grafts.

Objective:To study the antioxidant protective effects of different low-dose of insulin glargine on organs of burned rats with delayed resuscitation.Methods:Forty male Sprague-Dawley (SD) rats were randomly divided into sham group, delayed resuscitation control group, and insulin glargine 0.5, 1.0, and 2.0 U groups, with 8 rats in each group. The rats were immersed in hot water (95.0±0.5) ℃ for 15 s to establish the third-degree scald model with 30% total body surface area. The rats in the sham group were immersed in a 37 ℃ water bath for 15 s. Insulin glargine (0.5, 1.0, 2.0 U·kg -1·d -1) was injected subcutaneously in corresponding insulin glargine group 2 hours after injury, and the same amount of normal saline was injected intraperitoneally in the delayed resuscitation control group. Intraperitoneal injection of normal saline 40 mL/kg simulated delayed resuscitation 6 hours after injury in all groups. Abdominal aortic blood samples, heart and kidney tissue were collected immediately after simulating burn in the sham group, and 24 hours after burn in other four groups. The blood glucose, myocardial enzymes [lactate dehydrogenase (LDH), creatine kinase (CK), α-hydroxybutyrate dehydrogenase (α-HBDH), and aspartate aminotransferase (AST)] and renal function indexes [blood urea nitrogen (BUN) and serum creatinine (SCr)] were measured by spectrophotometry, and the isoenzyme MB of creatine kinase (CK-MB) level was determined by immunosuppression method to evaluate the effects of different low-dose insulin glargine intervention on blood glucose, cardiac and renal functions in scalded rats with delayed resuscitation. The oxidative and antioxidant indices [xanthine oxidase (XOD), myeloperoxidase (MPO), copper-zinc superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC)] from the heart and kidney tissues of rats were detected by spectrophotometry to analyze the antioxidant effects of different low-dose insulin glargine interventions. Results:Compared with the sham group, the blood glucose of the rats in the delayed resuscitation control group was significantly increased, the heart and kidney functions were significantly reduced, the oxidation capacity was enhanced, and the antioxidant indicators were significantly reduced. After the intervention of insulin glargine, with the increase of insulin glargine dose, the blood glucose, myocardial enzyme and renal function indicators of rats showed a gradual downward trend, the oxidation indicators continued to decrease, and the antioxidant indicators showed a gradual upward trend. When the dose was 2.0 U·kg -1·d -1, the blood glucose, LDH, CK, CK-MB, α-HBDH, AST, BUN, SCr, XOD and MPO were significantly lower than those in the delayed resuscitation control group [blood glucose (mmol/L): 5.91±0.25 vs. 11.76±0.36, LDH (U/L): 3 332.12±51.61 vs. 5 008.94±490.12, CK (kU/L): 0.49±0.03 vs. 0.85±0.04, CK-MB (U/L): 125.40±12.19 vs. 267.52±11.63, α-HBDH (U/L): 122.99±5.37 vs. 240.85±13.99, AST (U/L): 11.95±1.81 vs. 17.87±1.57, BUN (mmol/L): 4.72±0.15 vs. 7.16±0.34, SCr (μmol/L): 87.11±6.51 vs. 137.50±11.36, XOD (U/g): 166.29±3.27 vs. 204.90±4.82 in heart tissue, 63.51±1.46 vs. 79.69±1.75 in kidney tissue, MPO (U/g): 1.05±0.02 vs. 1.55±0.06 in heart tissue, 1.04±0.04 vs. 1.87±0.01 in kidney tissue, all P < 0.05], and CuZn-SOD, CAT, GSH-Px and T-AOC were significantly higher than those in the delayed resuscitation control group [CuZn-SOD (kU/g): 82.95±2.69 vs. 56.52±2.26 in heart tissue, 94.50±2.73 vs. 62.02±1.66 in kidney tissue, CAT (U/g): 36.07±2.01 vs. 15.15±2.22 in heart tissue, 184.49±4.53 vs. 156.02±3.96 in kidney tissue, GSH-Px (kU/g): 231.93±8.03 vs. 179.48±3.15 in heart tissue, 239.63±7.30 vs. 172.20±2.09 in kidney tissue, T-AOC (kU/g): 4.85±0.23 vs. 2.71±0.11 in heart tissue, 5.51±0.08 vs. 3.50±0.07 in kidney tissue, all P < 0.05]. Conclusion:Different low-dose of insulin glargine (≤2.0 U·kg -1·d -1) could exert antioxidant protection on the heart and kidney of rats with delayed resuscitation after burns, with a dose-dependent manner.

Objective:To observe the effects of medium and long-term insulin pretreatment on the activity of main oxidase and antioxidant enzyme in the myocardium of burned rats with delayed fluid resuscitation.Methods:According to random number table method, forty male Sprague-Dawley (SD) rats were divided into pseudo-burn group, burn delayed resuscitation group, insulin glargine pretreatment group and neutral protamine hagedorn (NPH) insulin pretreatment group, with 10 rats in each group. 30% total body surface area (TBSA) as Ⅲ degree scald model was prepared by bathing the back of rats in 95 ℃ hot water for 15 s; the rats in the pseudo-burn group were immersed in 37 ℃ warm water for 15 s as control. Insulin glargine pretreatment group, NPH insulin pretreatment group and burn delayed resuscitation group were injected subcutaneously with insulin glargine, NPH insulin, and normal saline 1.0 U·kg -1·d -1 2 hours after injury, and intraperitoneal injection of normal saline 40 mL/kg simulated delay resuscitation 6 hours after injury. The pseudo-burn group didn't receive medicine and delayed resuscitation. Abdominal aortic blood samples and heart tissue were collected immediately after simulating scald in the pseudo-burn group, and 24 hours after scald in three burn groups. Blood glucose, xanthine oxidase (XOD), myeloperoxidase (MPO), CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) of the heart tissue were determined by spectrophotometry. Results:Compared with the pseudo-burn group, the burn delayed resuscitation group have significantly higher blood glucose level and the XOD and MPO in the heart tissue, while significantly lower CuZn-SOD, CAT, and GSH-Px in the heart tissue. Compared with the burn delayed resuscitation group, insulin glargine pretreatment group and NPH insulin pretreatment group have lower blood glucose level and heart tissue XOD [blood glucose (mmol/L): 6.37±1.22, 6.66±1.45 vs. 9.47±0.80; XOD (U/g): 271.93 (261.59, 275.91), 285.32 (251.96, 297.29) vs. 363.37 (354.12, 377.76), all P < 0.05], while significantly higher heart tissue CuZn-SOD, CAT, and GSH-Px [CuZn-SOD (U/g): 0.13±0.01, 0.14±0.01 vs. 0.10±0.01; CAT (U/g): 29.17±7.28, 27.16±7.37 vs. 18.36±4.53; GSH-Px (U/g): 0.33 (0.16, 0.41), 0.30 (0.17, 0.41) vs. 0.07 (0.04, 0.11), all P < 0.05]. MPO activity in insulin glargine pretreatment group was significantly lower than that in burn delayed resuscitation group (U/g: 0.016±0.002 vs. 0.020±0.002, P < 0.05), but there was no significant difference between insulin pretreatment group and NPH insulin pretreatment group (U/g: 0.019±0.003 vs. 0.020±0.002, P > 0.05). There was no significant difference in the blood glucose, and activities of XOD, MPO, CAT, GSH-Px between insulin glargine pretreatment group and NPH insulin pretreatment group, but the activity of CuZn-SOD in NPH insulin pretreatment group was further higher than that in insulin glargine pretreatment group (U/g: 0.14±0.01 vs. 0.13±0.01, P < 0.05). Conclusions:Medium and long-term insulin pretreatment can improve the antioxidant capacity of myocardium in delayed resuscitation rats after burns, inhibit the production of reactive oxygen species and improve the scavenging capacity of reactive oxygen species. However, only CuZn-SOD activity is different between the two groups, and further study needs to be carried out to determine whether it is related to the type if insulin.

Negative pressure wound therapy with instillation (NPWTi) is used in the treatment of various types of wounds. A series of parameters related to NPWTi have not been unified yet, including flushing fluid selection, flushing mode, and rinsing fluid soaking time, negative pressure size, treatment time, etc. This paper reviews the research progress of these parameters.

Objective To investigate clinicopathological features,diagnosis and treatment of cutaneous Merkel cell carcinoma (MCC).Methods CNKI,Wanfang,Vip databases were searched for reported domestic cases of MCC from January 1,1986 to October 1,2017,and clinical data were collected,and retrospectively analyzed and summarized.Results During 31 years between 1986 and 2017,a total of 171 domestic cases of MCC were reported.There were 78 males and 93 females,and the ratio of male to female was 1:1.19.Of the 171 patients,136 (79.5％) were aged more than 50 years,and lesions mostly occurred on the head and face or extremities in 139 (81.3％) patients.Clinically,149 (87.1％) patients were misdiagnosed as tumor of unknown origin (89 cases,52％),malignant lymphoma (34 cases,19.9％),benign tumors (15 cases,8.8％) or non-tumor diseases (11 cases,6.4％).As for clinical stage,84 (49.1％) patients had stage Ⅰ MCC,and 49 (28.6％)had stage Ⅱ MCC.One patient received immunotherapy,and 165 patients underwent surgical resection,including 91 patients receiving surgery alone,24 patients treated with postoperative radiotherapy,19 patients treated with postoperative chemotherapy,and 31 patients receiving postoperative chemoradiotherapy.Five patients did not describe the treatment.Among 74 patients who were followed up after the surgery,one-year survival rate and five-year survival rate were 52.7％ and 6.8％ respectively.The five-year survival rate was 6.1％ in the patients with stage Ⅰ MCC,5.6％ in those with stage Ⅱ MCC,and 0 in those with stage Ⅲ and Ⅳ MCC.Conclusions In China,cutaneous MCC mostly occurs on the head,face,neck and extremities of the middle-aged or elderly,with a high misdiagnosis rate.Surgical excision combined with radiotherapy or chemotherapy is a frequently used treatment protocol in China,but the prognosis is always poor.