BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P＜0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95％confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95％CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95％CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95％CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4＞0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.

Objective: To compare the effects of height-desk-chair matching on the viewing distance of primary school students before and after intervention, so as to provide scientific basis for the hygiene management of desks and chairs. Methods: From April to June 2025, a random cluster sampling method was used to select 141 third grade students from three classes equipped with adjustable desks and chairs in a primary school in Hefei City for a height-desk-chair matching intervention study. The height of students desks and chairs was adjusted according to the standard height and height range specified in the Functional Sizes and Technical Requirements of Chairs and Tables for Educational Institutions (GB/T 3976-2014), with an intervention period of one week. Before and after the intervention, eye use data were measured by using the electronic smart device "Cloud Clip", while collecting data on vision data viewing distance, time spent using eyes at close range and outdoor time, desk and chair height, and physical examination. Linear regression analysis was used to investigate the factors related to viewing distance before the intervention of height-desk-chair matching, and a paired t-test was used to analyze the difference in viewing distance before and after the intervention. A mixed effects model was used to explore the effect of height desk and chair adaptation intervention on viewing distance. Results: The compliance rates for desk and chair adjustments before and after the intervention were 1.4% and 18.4%, respectively, with a statistically significant difference ( χ 2=22.84, P <0.01). The viewing distance increased from (30.48±5.01) cm before intervention to (32.06±5.75) cm post intervention, with a statistically significant difference ( t=4.57, P <0.01). The proportion of students meeting the viewing distance standard increased from 33.3% to 51.1%. The linear mixedeffects model results indicated that the association between height appropriate desk and chair interventions and viewing distance was statistically significant, regardless of whether covariates such as time spent using eyes at close range and outdoor time were adjusted ( β=-1.58, 95%CI = -2.25 to -0.91; β=-1.14, 95%CI =-1.85 to -0.43, both P <0.05). Conclusion Height adjusted desks and chairs, which can effectively increase the viewing distance for primary school students, has positive implications for improving healthy eye care behaviors among children and adolescents.

Objective To explore the predictive value of serum high-mobility group box protein B1(HMGB1)and soluble receptor for advanced glycation end-products(sRAGE)in the occurrence and short-term prognosis of sepsis-associated encephalopathy(SAE).Methods Clinical data of 228 patients with sepsis were retrospectively analyzed.According to the presence of SAE,patients were divided into the SAE group(96 cases)and the non-SAE group(132 cases).General clinical data,laboratory test results,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores,Sequential Organ Failure Assessment(SOFA)scores and serum HMGB1 and sRAGE levels were compared between the two groups.Multivariate Logistic regression analysis was performed to determine factors influencing SAE occurrence.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive ability of HMGB1,sRAGE and the HMGB1/sRAGE ratio to predict the occurrence and short-term prognosis of SAE.Kaplan-Meier survival curves were used to compare the 28-day mortality rates of SAE patients with different HMGB1 and sRAGE expression levels.Results Compared to the non-SAE group,patients in the SAE group exhibited elevated serum HMGB1 levels,decreased sRAGE levels and an increased HMGB1/sRAGE ratio(P＜0.05).The areas under the curve(AUC)for predicting SAE using HMGB1,sRAGE and the HMGB1/sRAGE ratio were 0.826(95%CI:0.770-0.872),0.682(95%CI:0.617-0.742)and 0.895(95%CI:0.848-0.932),respectively,indicating predictive value.Among the 96 SAE patients,52(54.2%)died within 28 days.There were no statistically significant differences in HMGB1,sRAGE and the HMGB1/sRAGE ratio between surviving and deceased patients(P＞0.05).Similarly,there were no significant differences in 28-day mortality rates between SAE patients with different HMGB1 or sRAGE expression levels.Conclusion Elevated serum HMGB1 and reduced sRAGE are of significant value in the auxiliary diagnosis of SAE,but have limited clinical predictive value for short-term prognosis.

Objective To explore the predictive value of serum high-mobility group box protein B1(HMGB1)and soluble receptor for advanced glycation end-products(sRAGE)in the occurrence and short-term prognosis of sepsis-associated encephalopathy(SAE).Methods Clinical data of 228 patients with sepsis were retrospectively analyzed.According to the presence of SAE,patients were divided into the SAE group(96 cases)and the non-SAE group(132 cases).General clinical data,laboratory test results,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ)scores,Sequential Organ Failure Assessment(SOFA)scores and serum HMGB1 and sRAGE levels were compared between the two groups.Multivariate Logistic regression analysis was performed to determine factors influencing SAE occurrence.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive ability of HMGB1,sRAGE and the HMGB1/sRAGE ratio to predict the occurrence and short-term prognosis of SAE.Kaplan-Meier survival curves were used to compare the 28-day mortality rates of SAE patients with different HMGB1 and sRAGE expression levels.Results Compared to the non-SAE group,patients in the SAE group exhibited elevated serum HMGB1 levels,decreased sRAGE levels and an increased HMGB1/sRAGE ratio(P＜0.05).The areas under the curve(AUC)for predicting SAE using HMGB1,sRAGE and the HMGB1/sRAGE ratio were 0.826(95%CI:0.770-0.872),0.682(95%CI:0.617-0.742)and 0.895(95%CI:0.848-0.932),respectively,indicating predictive value.Among the 96 SAE patients,52(54.2%)died within 28 days.There were no statistically significant differences in HMGB1,sRAGE and the HMGB1/sRAGE ratio between surviving and deceased patients(P＞0.05).Similarly,there were no significant differences in 28-day mortality rates between SAE patients with different HMGB1 or sRAGE expression levels.Conclusion Elevated serum HMGB1 and reduced sRAGE are of significant value in the auxiliary diagnosis of SAE,but have limited clinical predictive value for short-term prognosis.

Objective:To explore a staged repair procedure for whole foot skin degloving injury and evaluate the clinical outcome.Methods:From August 2020 to March 2023, a retrospective analysis was conducted on 20 patients, 12 males and 8 females, with who had whole foot skin avulsion injuries and were treated at the Department of Foot and Ankle Surgery, Ninth People's Hospital of Wuxi City. Nine injuries of foot skin avulsion were on the left feet and 11 on the right. All patients underwent a primary in situ replantation of the avulsed skin, and a stage-II surgery based on clinical manifestations and combined together with plantar pressure analysis in order to design a contralateral free medial plantar flap for reconstruction of the weight-bearing area of the affected foot. Eleven patients received the reconstructive surgery for forefoot weight-bearing area, and 9 had the reconstructive surgery for the heel weight-bearing area. The flap sizes ranged from 4 cm×4 cm to 13 cm×8 cm. All flap donor sites were closed with full-thickness skin grafts from ipsilateral thigh. Scheduled postoperative follow-ups at outpatient clinic were conducted to observe the flap survival, appearance and texture of the foot skin. American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot functional scores and the British Medical Research Council (BMRC) sensory function scale for flap sensation evaluation were used for assessment of the surgical outcomes, as well as the patient satisfaction. Pre- and postoperative plantar pressure analyses were performed to compare the weight-bearing area, load ratio and average plantar pressure. Statistical analysis was conducted using One-way ANOVA and Chi-square tests. P<0.05 was considered statistically significant. Results:The postoperative follow-up lasted for 10 to 24 months, with an average of 12.1 months. All 20 flaps survived. The flap swelling, appearance and wear resistance were good with AOFAS scores at 70 - 88 points. The sensation recovery reached S 2 to S 3. Patient satisfaction was excellent in 19 patients and good in 1 patient. The preoperative weight-bearing area was measured at 84 cm 2 to 140 cm 2, and 93 cm 2 to 145 cm 2 after surgery. The preoperative load ratio was 25% to 40%, and 30% to 43% after surgery. The preoperative plantar pressure was 185 grams/cm 2 to 356 grams/cm 2, and that was 205 grams/cm 2 to 381 grams/cm 2 after surgery. The postoperative weight bearing area, load ratio and mean plantar pressure of the patients were found all superior to those before surgery, with statistically significant differences ( P<0.05). Conclusion:In primary surgery, the avulsed skin is in situ replanted meanwhile have the original plantar skin preserved as much as possible. In the stage-II surgery, a contralateral medial free plantar flap is precisely designed to reconstruct the foot weight-bearing area, according to the healing of the in situ replanted skin and the wear resistance of the skin in weight-bearing area, and an analysis of plantar pressure should be performed. This is a reliable surgical procedure in the treatment of a degloving injury of whole foot.

Objective:To investigate the relationship between visual recovery and non-treponemal serologic test titers [tolulized red unheated serum test (TRUST) or rapid plasma reagin (RPR)] in patients with isolated ocular syphilis and those with ocular syphilis combined with neurosyphilis.Methods:A total of 35 ocular syphilis patients treated at the Department of Ophthalmology, the First Affiliated Hospital of Soochow University, and the Department of Dermatology, the Fifth People′s Hospital of Suzhou between 2016 and 2024 were enrolled. Pre-treatment serum TRUST/RPR and treponema pallidum particle agglutination (TPPA) assay results were collected for all 35 patients. Cerebrospinal fluid (CSF) biochemical, routine, TRUST/RPR, and TPPA results were obtained for 29 patients. Visual acuity (logMAR) before and after treatment was recorded for 21 patients (34 eyes). Pearson or Spearman correlation analysis was used to assess the relationship between pre-and post-treatment visual acuity, degree of visual recovery, and serum titers.Results:No significant differences in titer distribution were observed among the 35 ocular syphilis patients based on age or sex ( P>0.05). Among the 29 patients who underwent lumbar puncture, 17(58.62%) were diagnosed with ocular syphilis combined with neurosyphilis, while 12(41.38%) had isolated ocular syphilis. The proportion of patients with high pre-treatment serum titers did not differ significantly between the two groups ( P=0.294). The degree of post-treatment visual recovery showed a positive correlation with pre-treatment serum titers, indicating that higher initial titers were associated with better visual recovery (34 eyes, r=-0.302, P=0.081). Post-treatment visual acuity was positively correlated with pre-treatment visual acuity (34 eyes, r=0.547, P=0.001), suggesting that patients with poor baseline vision had worse post-treatment visual outcomes. The median visual improvement was logMAR 0.560 in the isolated ocular syphilis group and logMAR 0.202 in the neurosyphilis-combined group, with no significant difference between the two ( P=0.322). Conclusions:Ocular syphilis patients with higher pre-treatment titers exhibit better visual recovery, while poor post-treatment visual outcomes are associated with low baseline visual acuity.

BACKGROUND:Traditional methods of urinary tract reconstruction are limited by donor scarcity,high complication rates,and suboptimal functional recovery.Tissue engineering strategies offer new directions in this field.Since the urinary tract is mainly composed of muscle tissue,the key is to find suitable seed cells and efficiently induce them to differentiate into smooth muscle cells.Comparative studies on the efficacy of different smooth muscle cell induction regimens are still lacking. OBJECTIVE:To isolate,culture,and identify human urine-derived stem cells,and to compare the effects of two different induction protocols. METHODS:Human urine-derived stem cells were isolated from urine samples of 11 healthy adult volunteers by multiple centrifugations.Surface markers were identified by flow cytometry.The multi-directional differentiation potential of human urine-derived stem cells was verified through osteogenic and adipogenic differentiation.Differentiation was induced by transforming growth factor-β1 or transforming growth factor-β1 combined with platelet derived growth factor for 14 days.Immunofluorescence staining and western blot assay were employed to compare the expression differences of smooth muscle-specific proteins(α-SMA and SM22). RESULTS AND CONCLUSION:(1)Urine-derived stem cells were successfully isolated from the eight urine samples of healthy people.These cells exhibit a"rice grain"-like morphology and possess a robust proliferative capacity.(2)Urine-derived stem cells exhibited high expression of mesenchymal stem cell surface markers(CD73,CD90,and CD44)and extremely low expression of hematopoietic stem cell surface markers(CD34 and CD45).These cells did not express CD19,CD105,and HLA-DR.(3)After osteogenic and adipogenic differentiation,the formation of calcium nodules and lipid droplets was observed,with positive staining results from Alizarin Red S and Oil Red O staining.(4)After 14 days of smooth muscle induction culture,immunofluorescence staining revealed that the smooth muscle differentiation rate of urine-derived stem cells treated with a combination of transforming growth factor-β1 and platelet derived growth factor was significantly higher compared to those treated with transforming growth factor-β1 alone(P<0.005).(5)After 14 days of smooth muscle induction culture,western blot assay further demonstrated that the expression levels of α-SMA and SM22 in the transforming growth factor-β1/platelet derived growth factor group were significantly elevated compared to those in the transforming growth factor-β1 only group(P<0.005).These findings confirm that urine-derived stem cells can be non-invasively isolated using multiple rounds of centrifugation.Compared with transforming growth factor-β1 alone,the combination of transforming growth factor-β1 and platelet derived growth factor can improve the efficiency of inducing urine-derived stem cells to differentiate into smooth muscle cells.

Objective:To observe the stability of vertical dimension of occlusion (VDO) and mandibular position in full-mouth occlusal reconstruction subjects by means of digital occlusal analysis.Methods:Six subjects who had completed full-mouth occlusal reconstruction by intraoral functional generated path technique for more than three years in the Department of Prosthodontics, Peking University School and Hospital of Stomatology were enrolled for follow-up observation, all six patients were male, with an age of (53.6±8.4) years. The digital dentition model and occlusal contact at baseline and three years follow-up review after restoration were recorded by intraoral laser scanning, and the changes in occlusal surface morphology, occlusal contact area and mandibular position (mandibular overall deviation and mandibular reference plane average angle deviation) were measured in reverse engineering software. The Wilcoxon signed rank test was used to statistically analyze the changes of horizontal and vertical overbite of anterior teeth and VDO of posterior teeth between baseline and three years follow-up after reconstruction.Results:The prosthesis in the 6 subjects were intact at the time of follow-up, and there was no significant change in occlusal morphology compared with that at the baseline right after restoration delivery, and the occlusal contact in maximum intercuspid position was stable. The overall deviation of the lower jaw was (0.19±0.06) mm, and the angular deviation of the mandibular reference plane was 0.72°±0.38°. The chromatic scale of occlusal contact showed that the occlusal contact in some areas was heavier during the three years post-delivery, and the overbite of anterior teeth and the VDO of posterior teeth showed no statistical difference compared with that in the baseline (all P>0.05). Conclusions:This study suggests that the occlusal contact distribution and jaw position relationship can be maintained after 3 years of full-mouth occlusal reconstruction, and there is no significant change in the anterior overbite and VDO.

Objective:To explore a staged repair procedure for whole foot skin degloving injury and evaluate the clinical outcome.Methods:From August 2020 to March 2023, a retrospective analysis was conducted on 20 patients, 12 males and 8 females, with who had whole foot skin avulsion injuries and were treated at the Department of Foot and Ankle Surgery, Ninth People's Hospital of Wuxi City. Nine injuries of foot skin avulsion were on the left feet and 11 on the right. All patients underwent a primary in situ replantation of the avulsed skin, and a stage-II surgery based on clinical manifestations and combined together with plantar pressure analysis in order to design a contralateral free medial plantar flap for reconstruction of the weight-bearing area of the affected foot. Eleven patients received the reconstructive surgery for forefoot weight-bearing area, and 9 had the reconstructive surgery for the heel weight-bearing area. The flap sizes ranged from 4 cm×4 cm to 13 cm×8 cm. All flap donor sites were closed with full-thickness skin grafts from ipsilateral thigh. Scheduled postoperative follow-ups at outpatient clinic were conducted to observe the flap survival, appearance and texture of the foot skin. American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot functional scores and the British Medical Research Council (BMRC) sensory function scale for flap sensation evaluation were used for assessment of the surgical outcomes, as well as the patient satisfaction. Pre- and postoperative plantar pressure analyses were performed to compare the weight-bearing area, load ratio and average plantar pressure. Statistical analysis was conducted using One-way ANOVA and Chi-square tests. P<0.05 was considered statistically significant. Results:The postoperative follow-up lasted for 10 to 24 months, with an average of 12.1 months. All 20 flaps survived. The flap swelling, appearance and wear resistance were good with AOFAS scores at 70 - 88 points. The sensation recovery reached S 2 to S 3. Patient satisfaction was excellent in 19 patients and good in 1 patient. The preoperative weight-bearing area was measured at 84 cm 2 to 140 cm 2, and 93 cm 2 to 145 cm 2 after surgery. The preoperative load ratio was 25% to 40%, and 30% to 43% after surgery. The preoperative plantar pressure was 185 grams/cm 2 to 356 grams/cm 2, and that was 205 grams/cm 2 to 381 grams/cm 2 after surgery. The postoperative weight bearing area, load ratio and mean plantar pressure of the patients were found all superior to those before surgery, with statistically significant differences ( P<0.05). Conclusion:In primary surgery, the avulsed skin is in situ replanted meanwhile have the original plantar skin preserved as much as possible. In the stage-II surgery, a contralateral medial free plantar flap is precisely designed to reconstruct the foot weight-bearing area, according to the healing of the in situ replanted skin and the wear resistance of the skin in weight-bearing area, and an analysis of plantar pressure should be performed. This is a reliable surgical procedure in the treatment of a degloving injury of whole foot.