Background::Scleroderma is characterized by inflammation and fibrosis, predominantly occurring in the skin and extending to various parts of the body. The pathophysiology of scleroderma is multifaceted, with the current understanding including endothelial damage, inflammatory cell infiltration, and fibroblast activation in its progression. Nonetheless, the mechanism of cellular interactions and the precise spatial distribution of these cellular events within the fibrotic tissues remain elusive, highlighting a critical gap in our comprehensive understanding of scleroderma’s pathogenesis.Methods::In this study, we administered bleomycin intradermally to the dorsal skin of four individual murine models. Subsequently, skin tissues were harvested at predetermined intervals for comprehensive spatial transcriptomic analysis to determine the spatial dynamics influencing scleroderma pathogenesis. To validate the possible results from bioinformatic analysis, further in vitro and in vivo experiments were conducted. Results::Analysis of the spatial transcriptome revealed significant alterations in cell clusters during the progression of scleroderma. Gene Ontology analysis identified disruptions in lipid metabolism as the disease advanced. Pseudotime analysis provided evidence for a phenotypic transition from adipocytes to fibroblasts. In vitro studies demonstrated increased expression of Col1a1 and α-SMA as the disease progressed. These fibroblasts have been identified as key contributors to the increasing inflammation. Co-culturing TGF-β induced adipocytes with RAW264.7 cells resulted in overexpression of pro-inflammatory cytokines in the RAW264.7 cells. Both in vitro and in vivo experiments confirmed adipocyte loss and fibroblast formation, with transformed fibroblasts showing pronounced pro-inflammatory characteristics, highlighting their crucial role in the disease mechanism. Conclusions::Our study showed the spatial distribution and dynamic alterations of various cell types during scleroderma progression. Crucially, we identified the transformation of adipocytes into fibroblasts as a key factor promoting disease advancement. These emergent fibroblasts intensify inflammation, indicating that research on these cell clusters could reveal key scleroderma mechanisms and guide future therapies.

Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.

Objective:To investigate the efficacy of intravenous infusion of tranexamic acid(TXA)on perioperative blood loss in geriatric patients with hip fracture.Methods:In this retrospective study, 54 out of 95 patients with hip fracture aged from 65 years to 100 years, treated at the Department of Trauma and Osteology, West China Hospital of Sichuan University from June 2020 to June 2021 were finally enrolled.Their clinical data were collected.All patients underwent closed reduction PFNA surgery.They were divided into three groups: (1)Control group(n=18): intravenous infusion of normal saline at 30 min before surgery; (2)Single dose group(n=18): TXA(25 mg/kg)was intravenously injected at 30min before surgery; (3)multiple dose group(n=18): 25 mg/kg of TXA was intravenously injected at 30 min before surgery and 15 mg/kg injected again at 3 h and 6 h after surgery.Total blood loss and the incidence of postoperative deep venous thrombosis among 3 group patients were compared.Results:There were no statistically significant differences in gender, age, preoperative platelets, preoperative activated partial thrombin time and preoperative prothrombin time among control group, single dose group and multiple dose group(all P>0.05). Perioperative blood loss was estimated to be 620(330, 1080)ml, 380(270, 490)ml and 520(190, 750)ml in the control group, single dose group and multiple dose group, respectively, with statistical significance( H=8.666, P<0.05). Total blood loss in single dose group was less than in both control( P<0.05, with statistical significance)and in multiple groups( P>0.05, without statistical significance), and total blood loss in multiple dose group was lower than in control( P>0.05, without statistical significance), and higher than in single dose group( P>0.05, without statistical significance). Color ultrasonography was performed on the 1 st and 7 th day after surgery in 3 groups, and no deep venous thrombosis or pulmonary embolism was found in all groups. Conclusions:Intravenous infusion of TXA at half an hour before surgery can effectively reduce the total peri-operative blood loss without increasing the risk of thrombosis.A multiple preoperative intravenous drip of TXA should be cautious as compared with a single preoperative intravenous drip of TXA.

Objective To evaluate the valuse of endoscopic ultrasonography ( EUS ) for upper gastrointestinal submucosal lesions and the role of Photoshop in differentiating leiomyoma and stromal tumors. Methods Data of 656 patients with upper gastrointestinal submucosal lesions evaluated by EUS and receiving endoscopic submucosal dissection ( ESD ) from April 2010 to March 2015 were collected and retrospectively analyzed. The goldern standard for lesions size and origin was the intraoperative diagnosis of ESD, and that of the type of lesions ( leiomyoma, stromal tumor, ectopic pancreas, lipoma, etc.) was pathological and immunohistochemical finding. The consistency of diagnosis of the EUS was evaluated. In addition, Photoshop was used to differentiate diagnosis of leiomyoma and stromal tumors which were confirmed by pathology and immunohistochemistry. Results The consistency in diagnosing the size and lesion origins was 92?56%(560/605) and 88?43%(535/605)between EUS and ESD intraoperative result. The consistency in pathological types of EUS was 79?34%(480/605). Photoshop was used to analyze the EUS images of 177 stromal tumor and 241 leiomyoma. The gray value of stromal tumor was significantly higher than that of leiomyoma(59?97 VS 39?39, t=43?27, P<0?05).The echo of stromal tumor was higher. The standard deviation of gray value of leiomyoma were significantly lower than that of the stromal tumor ( 4?81 VS 5?42, t = 2?83, P < 0?05 ) , indicating the echo uniformity of leiomyoma was better. Conclusion EUS shows high accuracy rate for upper gastrointestinal submucosal lesions, providing more accurate basis for endoscopic therapy. EUS combined with Photoshop is helpful for differentiating stromal tumor from leiomyoma.

Objective To explore the causes,management and prevention of major blood vessel injury during urological laparoscopic surgery.Methods Six cases of major blood vessel injuries happened in 1700 laparoscopic surgeries from January 2007 to July 2011.All of the cases were males.Patient age was (53 ± 14) years.There were 4 extraperitoneal and 2 transperitoneal procedures including 3 adrenalectomies,1 radical cystectomy,1 radical prostatectomy and 1 radical nephrectomy.There were lacerations in 3 cases of vena cava,2 cases of external iliac vein and one case of renal vein.The length of laceration was (0.68 ±0.29) cm and blood lost was (114 ++ 79) ml.Results Five of the patients were managed with laparoscopic techniques by suction compressing bleeding sites,dissecting related vessels,adding extra trocar and repairing laceration by suturing in four cases and clipping bleeding site in one case.The bleeding control management lasted (21.0 ± 5.6) min.One laparoscopic adrenalectomty for the treatment of pheochromocytoma converted to open surgery because of increasing blood pressure.All the patients were followed up for (4 ± 2) months.No more related complication occurred.Conclusions Lymph node dissection,local adhesion and energy source are the main causes for blood vascular injuries.This kind of injuries may occur at any stages during a laparoscopic surgery and laparoscopic repairing is safe and feasible.

Objective To evaluate endoscopic ultrasonography (EUS) for diagnosis and treatment of ectopic pancreas in upper gastrointestinal tract.Methods Data of 52 patients with ectopic pancreas diagnosed by EUS and confirmed by pathological examination were reviewed.The feature of EUS image and diagnostic accuracy were retrospectively analyzed.Results Out of 52 patients, 41 (78.85% ) were pathologically diagnosed as having ectopic pancreas, 6 were stromal tumors, 4 were leiomyoma and 1 was nerve sheath tumor.All ectopic pancreases presented as protruding lesions, in which 37 were located at gastric antrum, 2 in duodenum, 1 in gastric body and 1 in gastric fundus.Under EUS, 1 case appeared as hyperechoic, 10 as isoechoic, 18 as hypoechoic and 12 as mixed echoic.The lesion involved mucosa in 2 cases, muscularis mu-cosae in 8, submucosa in 30 and muscularis propria in 1, in which 15 cases from submucosa underwent endoscopic resection.Bleeding occurred in 2 cases and no other complications occurred.There was one relapse during the 6 months of followed-up.Conclusion EUS is valuable and safe for the diagnosis of ectopic pancreas in upper gastrointestinal tract.Depth of lesions revealed by EUS can help further treatment.

Objective To discuss the surgical treatment of contracted bladder caused by ketamine abuse. Methods Twenty-five ketamine male abusers were included in this study.The ages were from 19 to 28 years old and mean age was 24 years old.AIl of them had abused ketamine history for 0.7 tO 4.0 years,and presented with severe lower urinary tract symptoms.including severe frequency,urgency,urge incontinence,and painful haematuria.Urine cultures were negative.Hepatic function and renal function were normal.B ultrasound examination of 23 cases demonstrated the presence of bilateral hydronephrosis,the separation of renal pelvic was(1.8±0.7)cm.B ultrasound examination of 22 cases demonstrated residual urine was 45-1 50 ml,mean 80 m1.Twenty-three IVU investigations demonstrated the presence of bilateral hydronephrosis with calyces renales minores cycloidal expansion and bladder contraction.All the patients took the urodynamies with bladder capacity was (89±34)ml,end filling detrusor pressure was(48±26)cm H2O,Qmax was(7.8±2.3)ml/s,residual urine volume was(82±47)m1.All patients had cystoscopies and random biopsies performed showed ulcerative cystitis only.All patients were required to withdraw the narcotics and the experimental medicines were given without symptoms alleviated.Sigmoid cystoplasty was performed in all the 25 patients. Results The mean follow up was 18 months(rang 6 to 36).Compared with that before operation, bladder capacity increased to (375 ±53)ml, end filling detrusor pressure reduced to( 13 ±9)cm H2O, Qmax increased to(17.6±5.8)ml/s, residual urine volume reduced to(20±10)ml.Compared with the preoperative, there were statistically significant differences.There was no complained of urinary incontinence, enuresis, frequency, urgency.Urine routine examination was normal.IVU showed the vesicoureteral reflux disappeared in all patients, and calyces renales no expansion or calyces renales minores light degree expansion.B ultrasound examination that the separation of renal collecting was(1.0 ±0.5)cm. Conclusions Sigmoidcystoplasty could increase bladder capacity and compliance, lower the intravesieal pressure.It could improve the patients' quality of life.

Objects: To investigate the behavior of gastric electrical activity in patients with gastrointestinal stromal tumor(GIST) to identify the influences of GIST on the normal gastric electrical activity. Methods: The electrogastrogram (EGG) parameters of 27 patients with gastric GIST (GIST group) and 30 healthy volunteers (control group) were detected by the multi-channel electrogastrogram and the data were analyzed. Results: The values of postprandial mean frequency (MF), mean amplitude (MA) and the percentage of normal slow wave (N%) were increased, and the percentage of bradygastria (B%) was decreased than those of the fasting in control group(P < 0.05 or P < 0.01). However, those postprandial parameter changes were not found in GIST group(P > 0.05). Compared with control group, the fasting MF and MA increased, the fasting N% of lead 1, 3, 4 and postprandial N% decreased, both percentages of fasting and postprandial tachygastria (T%) increased in GIST group (P < 0.01). The tachygastria incidence was significantly higher in GIST group than that of control (66.7% vs 3.3%, P <0.05). Conclusion: The gastric electrical activity was affected by the existence of GIST. The abnormal gastric electrical rhythm displayed mainly as tachygastria.

Objective To investigate the serum concentration of serum Fas(sFas) in patients with Graves' disease(GD) before and after ~(131)I therapy.Methods Serum levels of sFas were measured with enzyme linked-immuno-sorbent assay(ELISA) in 61 patients before and after ~(131)I therapy,and the results were compared with that the control subjects.Results The concentration of sFas was significantly higher in GD patients compared with that in the control subjects[(174.8?94.6)ng/L vs (96.6?10.2)ng/L,P0.05],and was significantly lower in patients with euthyroidism after 131 I therapy[(111.2?13.2)ng/L,P

Objective To evaluate the damaging degree of hepatic cell in the patients with hepatocirrhosis. Methods 30 cases of hepatocirrhosis and 15 cases of normal controls were performed the dynamic imaging with 99mTc-EHIDA. By the three compartmental model configurations, we acquired the time-activity curers of the liver cell,and calculated the function indexes liver cell extraction and excretion. Results The peak time and mean residence time in the hepatocirrhosis groups were higher than those in the normal controls(P