Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

Objective:To explore the effects of smoking on peripheral regulatory T cells (Tregs), transforming growth factor beta1 (TGF-β 1) and interleukin-10 (IL-10) in elderly patients with non-small cell lung cancer (NSCLC). Methods:This was a cross-sectional study. A total of 43 elderly patients (≥60 years old) who were hospitalized in the Department of Geriatrics Medicine, Guangzhou First People′s Hospital from January 2018 to December 2024 and were newly diagnosed with NSCLC were recruited. According to smoking history, patients were divided into non-smoking group (15 cases), low smoking group (13 cases, smoking index<400) and high smoking group (15 cases, smoking index≥400). Venous blood samples were collected from participants, plasma and cells were separated. Flow cytometry was used to measure the proportions of Tregs and the expression of forkhead box P3 (Foxp3) in peripheral blood. Plasma levels of TGF-β 1 and IL-10 were measured by enzyme-linked immunosorbent assay. The effects of smoking on peripheral Tregs, TGF-β 1, and IL-10 in elderly patients with NSCLC were analyzed. Data were analyzed by one-way ANOVA, rank-sum test, and Fisher′s exact test. Results:The proportions of Tregs in non-smoking group, low smoking group and high smoking group were 2.50% (2.32%, 2.81%), 2.83% (2.48%, 3.72%), and 3.01% (2.37%, 3.73%), respectively, and there were no statistically significant differences among the three groups ( H=3.845, P>0.05). The proportions of Foxp3 +Tregs were (3.72±0.84)%, (4.64±1.10)%, and (4.68±1.27%), respectively. The mean fluorescence intensities (MFI) of Foxp3 were 123.0 (108.0, 128.0), 131.0 (123.5, 350.0), and 222.0 (141.0, 311.0), respectively. Both the proportions of Foxp3 +Tregs and the MFI of Foxp3 were higher in low smoking group and high smoking group than those in non-smoking group (all P<0.05). However, there were no significant differences between low smoking group and high smoking group (all P>0.05). The concentrations of IL-10 were 2.27 (1.42, 3.95), 3.42 (2.30, 5.08), and 3.26 (2.35, 6.28) ng/L, respectively. There were no statistically significant differences among the three groups ( H=2.930, P>0.05). The concentrations of TGF-β 1 were (10.72±9.37), (13.46±10.39), and (25.28±16.67) ng/ml, respectively. The concentration of TGF-β 1 in high smoking group was higher than that in non-smoking group and low smoking group (all P<0.05). However, there was no statistically significant difference between low smoking group and non-smoking group ( P>0.05). Conclusions:Smoking intensity may be correlated with the immunosuppressive function of Tregs in elderly patients with NSCLC. Higher smoking levels are associated with increased Foxp3 expression in Tregs and elevated plasma levels of TGF-β 1, potentially enhancing the immunosuppressive function of Tregs.

Objective:To assess the association between temperature and risk of animal injury, and identifying vulnerable populations.Methods:Based on a time-stratified case-crossover design, the number of animal injuries monitored in hospitals of Guangdong Provincial Injury Surveillance System in 2011 and 2015-2016 was included, and the daily meteorological data were derived from the fifth generation of European ReAnalysis-Land, which was produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression combined with a distributed lagged nonlinear model was applied to analyze the association of temperature and animal-specific injuries. We also conducted stratified analysis by region, sex, age, occupation, and location of injury occurrence.Results:There was an almost linear relationship between temperature and the occurrence of animal injury. The excess risk ( ER) of animal injury was 2.65% (95% CI: 2.27%-3.04%) for a 1 ℃ rise in temperature with much higher risk of occurrence ( ER=9.34%, 95% CI: 7.57%-11.13%) for non-mammalian injury than that for mammalian injuries ( ER=2.30%, 95% CI: 1.90%-2.70%). Stratified analysis revealed that the occurrence of animal injury was more susceptible to temperature influences in urban ( ER=2.78%, 95% CI: 2.35%-3.21%), female ( ER=2.71%, 95% CI: 2.16%-3.27%), the elderly aged 60 years and above ( ER=3.05%, 95% CI: 1.65%- 4.47%), farmer ( ER=4.66%, 95% CI: 3.03%-6.32%) and agricultural area ( ER=10.63%, 95% CI: 7.57%-13.79%) than their correspondents. In terms of mammalian injury, dog bites showed the highest risk ( ER=2.71%, 95% CI: 2.12%-3.30%). In terms of non-mammalian,snake injuries were highly influenced by temperature ( ER=16.74%, 95% CI: 11.33%-22.40%). Conclusions:The ambient temperature rises could increase the risk of animal injury with much higher risk for non-mammalian than that for mammalian injuries. Our findings suggest that global warming may increase the risk and disease burden from animal injuries.

Objective:To explore the feasibility and effect on the reconstruction of whole hand degloving injury by transfer of nerved tissue flaps in staged surgery.Methods:A retrospective study was conducted on the clinical data of 5 patients who suffered whole hand degloving injury and underwent staged reconstructive surgery with nerved tissue flaps, from December 2018 to December 2022 in the Department of Hand Surgery, Longgang Orthopaedics Hospital of Shenzhen. The patients were 4 males and 1 female, aged 22-45 years. Two of the whole-hand degloved injuries were left hands and 3 of right. Two patients had the whole-hand degloving injury combined with a fracture of distal phalangeal tuberosity, and 1 was complicated with partial rupture of the extensor tendon insertion. Areas of the whole hand degloving injury ranged from 215 cm 2 to 480 cm 2, the size of the hallux nail flaps for reconstruction of thumbs ranged from 54 cm 2 to 104 cm 2, the size of the hallux nail flaps for reconstruction of index fingers ranged from 65 cm 2 to 133 cm 2, and the size of the flaps for reconstruction of all the defects of hands ranged from 119 cm 2 to 255 cm 2. In primary surgery, the thumbs, index fingers and the first webs were reconstructed with bilateral hallux nail flaps to shape the appearance and gain the sensation function. Meanwhile, a single and large defect was created from the defects of hand by bundling up the middle, ring and little fingers together with the all the defects in both palmar and dorsal hand. Then an anterolateral thigh flap (ALTF) was used to have the created single defect wrapped together. Donor sites of the bilateral hallux nail flap were reconstructed with a lobulated ALTF from the other side or with bilateral peroneal artery perforator flaps. Donor sites of the ALTF and peroneal artery perforator flap were pulled and sutured. After the hallux nail flaps and ALTFs of the affected hands had survived and stabilised, multiple staged surgery were then carried out to firstly reconstruct the ring and little fingers, and followed by the middle and ring fingers in turns from the artificial syndactyly created in the primary surgery. In the final stage of surgery, skin of the radial side of middle and ring finger-pulps and the ulnar little finger-pulp were replaced by lateral toe flaps to reconstruct the sensations of the main sensory zones of middle, ring and little finger-pulps. Thereafter, the shape, TPD and finger extension and flexions were observed and evaluated through the postoperative follow-up, at the outpatient clinic according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. The appearance and function of the donor sites in both feet were evaluated with the Maryland foot score. Results:All flaps survived after surgery. Postoperative follow-up lasted up to 14 to 48 months after the last surgery. The appearance of fingers was satisfactory with good function. TPD of thumbs and index finger-pulps had achieved up to 6-8 mm, and 3-8 mm in the main sensory zones of middle, ring and little finger-pulps. TPD in the non-major sensory zones of middle, ring and little finger-pulps was found at 10-14 mm, which scored 13 to 14 and rated as excellent according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. Only a linear scar left in the donor site of thigh. As the appearance of the flaps on the feet was not bloated and there was no obvious abnormality in walking and running, therefore the function of feet scored up to 96 to 97 and rated excellent according to the Maryland foot score.Conclusion:A multi-staged reconstruction of a whole hand degloving injury with nerved tissue flaps not only achieves satisfactory digital and hand appearance, but also with good function. There is no obvious effect on the appearance and function of the donor sites. This surgical strategy is novel in the reconstruction of a whole hand degloving injury.

Objective:To assess the association between temperature and risk of animal injury, and identifying vulnerable populations.Methods:Based on a time-stratified case-crossover design, the number of animal injuries monitored in hospitals of Guangdong Provincial Injury Surveillance System in 2011 and 2015-2016 was included, and the daily meteorological data were derived from the fifth generation of European ReAnalysis-Land, which was produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression combined with a distributed lagged nonlinear model was applied to analyze the association of temperature and animal-specific injuries. We also conducted stratified analysis by region, sex, age, occupation, and location of injury occurrence.Results:There was an almost linear relationship between temperature and the occurrence of animal injury. The excess risk ( ER) of animal injury was 2.65% (95% CI: 2.27%-3.04%) for a 1 ℃ rise in temperature with much higher risk of occurrence ( ER=9.34%, 95% CI: 7.57%-11.13%) for non-mammalian injury than that for mammalian injuries ( ER=2.30%, 95% CI: 1.90%-2.70%). Stratified analysis revealed that the occurrence of animal injury was more susceptible to temperature influences in urban ( ER=2.78%, 95% CI: 2.35%-3.21%), female ( ER=2.71%, 95% CI: 2.16%-3.27%), the elderly aged 60 years and above ( ER=3.05%, 95% CI: 1.65%- 4.47%), farmer ( ER=4.66%, 95% CI: 3.03%-6.32%) and agricultural area ( ER=10.63%, 95% CI: 7.57%-13.79%) than their correspondents. In terms of mammalian injury, dog bites showed the highest risk ( ER=2.71%, 95% CI: 2.12%-3.30%). In terms of non-mammalian,snake injuries were highly influenced by temperature ( ER=16.74%, 95% CI: 11.33%-22.40%). Conclusions:The ambient temperature rises could increase the risk of animal injury with much higher risk for non-mammalian than that for mammalian injuries. Our findings suggest that global warming may increase the risk and disease burden from animal injuries.

Objective To explore the influencing factors of immune-associated thyroid dysfunction caused by sintilimab treatment in solid tumors and construct a prediction model.Methods Medical records of patients diagnosed with solid tumors and treated with sintilimab at Peking University People's Hospital(Xizhimen Campus,Tongzhou Campus,Shijiazhuang Campus)from January 2023 to September 2024 were collected to explore the influencing factors that caused immune-related thyroid dysfunction using univariate and multifactorial binary logistic regression analyses and to establish a prediction model.The predictive effect of the model was assessed using the receiver operating characteristic(ROC)curve.Results A total of 120 patients were included,and 33 presented with immune-related thyroid dysfunction.Multifactorial logistic regression analysis revealed that thyroid-stimulating hormone(TSH)[OR=2.470,95%CI=(1.279,4.771)]and treatment cycles[OR=1.298,95%CI=(1.117,1.509)]were independent risk factors for the occurrence of immune-associated thyroid dysfunction,and the difference was statistically significant(P＜0.05).The area under the ROC curve was(0.897±0.043)[95%CI=(0.813,0.981)],the Yoden index was 0.703,and the model prediction accuracy was 86.5%.Conclusion The risk of immune-related thyroid dysfunction caused by sintilimab is high,and TSH and treatment cycle are the influencing factors,and the constructed model has certain predictive value and is of reference significance.

Objective:To explore the effects of smoking on peripheral regulatory T cells (Tregs), transforming growth factor beta1 (TGF-β 1) and interleukin-10 (IL-10) in elderly patients with non-small cell lung cancer (NSCLC). Methods:This was a cross-sectional study. A total of 43 elderly patients (≥60 years old) who were hospitalized in the Department of Geriatrics Medicine, Guangzhou First People′s Hospital from January 2018 to December 2024 and were newly diagnosed with NSCLC were recruited. According to smoking history, patients were divided into non-smoking group (15 cases), low smoking group (13 cases, smoking index<400) and high smoking group (15 cases, smoking index≥400). Venous blood samples were collected from participants, plasma and cells were separated. Flow cytometry was used to measure the proportions of Tregs and the expression of forkhead box P3 (Foxp3) in peripheral blood. Plasma levels of TGF-β 1 and IL-10 were measured by enzyme-linked immunosorbent assay. The effects of smoking on peripheral Tregs, TGF-β 1, and IL-10 in elderly patients with NSCLC were analyzed. Data were analyzed by one-way ANOVA, rank-sum test, and Fisher′s exact test. Results:The proportions of Tregs in non-smoking group, low smoking group and high smoking group were 2.50% (2.32%, 2.81%), 2.83% (2.48%, 3.72%), and 3.01% (2.37%, 3.73%), respectively, and there were no statistically significant differences among the three groups ( H=3.845, P>0.05). The proportions of Foxp3 +Tregs were (3.72±0.84)%, (4.64±1.10)%, and (4.68±1.27%), respectively. The mean fluorescence intensities (MFI) of Foxp3 were 123.0 (108.0, 128.0), 131.0 (123.5, 350.0), and 222.0 (141.0, 311.0), respectively. Both the proportions of Foxp3 +Tregs and the MFI of Foxp3 were higher in low smoking group and high smoking group than those in non-smoking group (all P<0.05). However, there were no significant differences between low smoking group and high smoking group (all P>0.05). The concentrations of IL-10 were 2.27 (1.42, 3.95), 3.42 (2.30, 5.08), and 3.26 (2.35, 6.28) ng/L, respectively. There were no statistically significant differences among the three groups ( H=2.930, P>0.05). The concentrations of TGF-β 1 were (10.72±9.37), (13.46±10.39), and (25.28±16.67) ng/ml, respectively. The concentration of TGF-β 1 in high smoking group was higher than that in non-smoking group and low smoking group (all P<0.05). However, there was no statistically significant difference between low smoking group and non-smoking group ( P>0.05). Conclusions:Smoking intensity may be correlated with the immunosuppressive function of Tregs in elderly patients with NSCLC. Higher smoking levels are associated with increased Foxp3 expression in Tregs and elevated plasma levels of TGF-β 1, potentially enhancing the immunosuppressive function of Tregs.

Objective:To explore the feasibility and effect on the reconstruction of whole hand degloving injury by transfer of nerved tissue flaps in staged surgery.Methods:A retrospective study was conducted on the clinical data of 5 patients who suffered whole hand degloving injury and underwent staged reconstructive surgery with nerved tissue flaps, from December 2018 to December 2022 in the Department of Hand Surgery, Longgang Orthopaedics Hospital of Shenzhen. The patients were 4 males and 1 female, aged 22-45 years. Two of the whole-hand degloved injuries were left hands and 3 of right. Two patients had the whole-hand degloving injury combined with a fracture of distal phalangeal tuberosity, and 1 was complicated with partial rupture of the extensor tendon insertion. Areas of the whole hand degloving injury ranged from 215 cm 2 to 480 cm 2, the size of the hallux nail flaps for reconstruction of thumbs ranged from 54 cm 2 to 104 cm 2, the size of the hallux nail flaps for reconstruction of index fingers ranged from 65 cm 2 to 133 cm 2, and the size of the flaps for reconstruction of all the defects of hands ranged from 119 cm 2 to 255 cm 2. In primary surgery, the thumbs, index fingers and the first webs were reconstructed with bilateral hallux nail flaps to shape the appearance and gain the sensation function. Meanwhile, a single and large defect was created from the defects of hand by bundling up the middle, ring and little fingers together with the all the defects in both palmar and dorsal hand. Then an anterolateral thigh flap (ALTF) was used to have the created single defect wrapped together. Donor sites of the bilateral hallux nail flap were reconstructed with a lobulated ALTF from the other side or with bilateral peroneal artery perforator flaps. Donor sites of the ALTF and peroneal artery perforator flap were pulled and sutured. After the hallux nail flaps and ALTFs of the affected hands had survived and stabilised, multiple staged surgery were then carried out to firstly reconstruct the ring and little fingers, and followed by the middle and ring fingers in turns from the artificial syndactyly created in the primary surgery. In the final stage of surgery, skin of the radial side of middle and ring finger-pulps and the ulnar little finger-pulp were replaced by lateral toe flaps to reconstruct the sensations of the main sensory zones of middle, ring and little finger-pulps. Thereafter, the shape, TPD and finger extension and flexions were observed and evaluated through the postoperative follow-up, at the outpatient clinic according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. The appearance and function of the donor sites in both feet were evaluated with the Maryland foot score. Results:All flaps survived after surgery. Postoperative follow-up lasted up to 14 to 48 months after the last surgery. The appearance of fingers was satisfactory with good function. TPD of thumbs and index finger-pulps had achieved up to 6-8 mm, and 3-8 mm in the main sensory zones of middle, ring and little finger-pulps. TPD in the non-major sensory zones of middle, ring and little finger-pulps was found at 10-14 mm, which scored 13 to 14 and rated as excellent according to the Evaluation Standard of Thumb and Finger Reconstruction Function of the Hand Surgery Society of the Chinese Medical Association. Only a linear scar left in the donor site of thigh. As the appearance of the flaps on the feet was not bloated and there was no obvious abnormality in walking and running, therefore the function of feet scored up to 96 to 97 and rated excellent according to the Maryland foot score.Conclusion:A multi-staged reconstruction of a whole hand degloving injury with nerved tissue flaps not only achieves satisfactory digital and hand appearance, but also with good function. There is no obvious effect on the appearance and function of the donor sites. This surgical strategy is novel in the reconstruction of a whole hand degloving injury.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

ObjectiveTo investigate the relationship between serum 25(OH)D and gestational diabetes mellitus in the second trimester (GDM), to analyze the interaction effect of key risk factors, so as to provide a basis for clinical personalized vitamin D supplementation. MethodsA total of 266 pregnant women who registered and took regular obstetric check-ups in Shanghai Pudong New Area Health Care Hospital for Women and Children from June to December 2022, were selected as the research subjects. According to the results of oral glucose tolerance test (OGTT), the subjects were divided into the GDM group (131) and control group (135). The level of serum 25(OH)D at the time of OGTT were detected and other clinical indicators were followed up. ResultsThe age, systolic blood pressure in early pregnancy, pre-pregnancy BMI, FPG, OGTT 1-hour and 2-hour glucose, GHb, HOMA-IR, TG, AST, Cr, D-D, FDP and SF at 35 weeks’ gestation of the pregnant women were higher in the GDM group than that of the pregnant women in the normal group, while gestational weight gain and serum 25(OH)D level were significantly lower than that of the pregnant women in the normal group. Serum 25(OH)D was negatively correlated with HOMA-IR and WBS’s, but positively correlated with TG and ALT. Serum 25(OH)D was non-linearly correlated with the risk of GDM in an inverted J-shape, and there was an interaction effect of advanced age, pre-pregnancy obesity and vitamin D deficiency on the risk of GDM. ConclusionVitamin D is non-linearly associated with the risk of GDM. The risk of GDM is significantly reduced when serum 25(OH)D level ≥30 ng∙mL^-1.