Functional characterization of TRAP1-like protein involved in modulating fibrotic processes mediated by TGF-ß/Smad signaling in hypertrophic scar fibroblasts.

The transforming growth factor-ß1 (TGF-ß)-mediated signaling pathway is believed to be closely associated with wound healing and scar formation, in which TRAP1-like protein (TLP) plays a role in regulating the balance of Smad2 vs. Smad3 signaling. Our previous study revealed the relation between TLP and collagen synthesis in normal human skin fibroblasts. Here, we present a detailed analysis of the effects of TLP on the process of hypertrophic scar formation and contraction. To explore and verify a contribution of TLP to the pathological mechanism of hypertrophic scar fibroblasts (HSFb), we constructed lentiviral vectors that either overexpressed TLP or encoded small hairpin RNAs (shRNAs) targeting TLP, then we transfected them into HSFb. TLP knockdown in HSFb resulted in reduced levels of cell contraction, type I and type III collagen mRNA transcripts and protein expression, and higher levels of fibronectin (FN) compared to control groups. In addition, knockdown of TLP promoted the phosphorylation of Smad3 but repressed Smad2 and Erk-1/2 phosphorylation in human hypertrophic scar fibroblasts compared to control groups. The reduction of TLP did not interfere with HSF proliferative ability, but exogenous TLP cooperated with TGF-ß1 to increase cell viability. Together, our findings demonstrate evidence for a contribution of TLP expression in hypertrophic scar formation and contraction.

The clinical applications of D-type parastomal hernia repair surgery.

OBJECTIVE: This study investigated the use of a modified laparoscopic repair of paraostomy hernia technique, called "D-Type parastomal hernia repair surgery" which combines abdominal wall and extraperitoneal stoma reconstruction, in patients with parastomal hernia (PSH) following colorectal stoma surgery. The aim was to determine whether D-type parastomal hernia repair surgery is a promising surgical approach compared to the traditional laparoscopic repair technique (Sugarbaker method) for patients with PSH. METHODS: PSH patients were selected and retrospectively divided into two groups: the study group underwent D-type parastomal hernia repair, while the control group underwent laparoscopic Sugarbaker repair. Clinical data from both groups were analyzed. RESULT: Compared to control group (n = 68), the study group undergoing D-type stoma lateral hernia repair had significant increase in total operative time (98.82 ± 12.37 min vs 124.61 ± 34.99 min, p < 0.001). The study group also showed better postoperative stoma bowel function scores in sensory ability, frequency of bowel movements, and clothing cleanliness without a stoma bag (p = 0.037, 0.001, 0.002). The treatment cost was significantly higher in the control group (3899.97 ± 260.00$ vs 3215.91 ± 230.03$, p < 0.001). The postoperative recurrence rate in the control group was 26.4%, while in the study group, it was 4.3%, with a significant statistical difference (p = 0.024). In terms of long-term postoperative complications, the study group had an overall lower incidence compared to the control group (p = 0.035). Other parameters showed no significant differences between the two groups. CONCLUSION: The study suggests that D-type parastomal hernia repair surgery is a safe and feasible procedure. Compared to traditional surgery, it can reduce the recurrence of lateral hernia, improve postoperative stoma bowel function, and save medical resources.

Meta-analysis of temporary ileostomy versus colostomy for colorectal anastomoses.

BACKGROUND/AIMS: Defunctioning stoma is a common surgical procedure, it is now generally acknowledged that defunctioning stoma significantly reduce the rates of complications in colorectal surgery, but the choice of temporary ileostomy or temporary colostomy for defunctioning colorectal anastomoses remains controversial. This meta-analysis evaluated two types of defunctioning stoma to determine whether one is superior to the other. METHODOLOGY: Studies and relevant literatures comparing temporary ileostomy with temporary colostomy for defunctioning colorectal anastomoses were searched though PubMed, Embase and The Cochrane Library. The rates of complications were pooled and compared using a meta-analysis. The risk ratios were calculated with 95% confidence intervals to evaluate the safety and efficacy of each technique. RESULTS: Five randomized controlled trials and seven non-randomized studies were included, with 1687 patients in total. The meta-analysis of the RCTs demonstrated a lower risk of stoma prolapse (RR 0.15; 95% CI: 0.04-0.48, p = 0.001) in the temporary ileostomy group. Meta-analysis of the non-randomized studies showed a lower risk of stoma prolapse (RR 0.26; 95% CI 0.10-0.67, p = 0.005) and wound infection after stoma closure (RR 0.28; 95% CI 0.5-0.52, p < 0.0001) in the temporary ileostomy group. No other statistically significant difference was observed for complications. CONCLUSIONS: Each type of defunctioning stoma has its advantages and disadvantages, and there is not a strong evidence for the superiority of one temporary stoma over another for colorectal anastomoses. According to this, large scale RCTs and high quality studies are needed to conduct.

[Surgical site infection after colorectal surgery in China from 2018 to 2020].

Objective: This study aims to survey the incidence of surgical site infection (SSI) in China and to analyze its risk factors, so as to prevent and control SSI after colorectal surgery. Methods: An observative study was conducted. Based on a program of Chinese SSI Surveillance from 2018 to 2020, the clinical data of all adult patients undergoing colorectal surgery during this time period were extracted. These included demographic characteristics and perioperative clinical parameters. Minors, pregnant women, obstetric or gynecological surgery, urological system surgery, retroperitoneal surgery, resection of superficial soft tissue masses, and mesh or other implants were excluded. A total of 2122 patients undergoing colorectal surgery from 50 hospitals were included, including 1252 males and 870 females. The median age was 63 (16) years and the median BMI was 23 (4.58) kg/m2. The primary outcome was the incidence of SSI within 30 days after colorectal surgery. The secondary outcomes were mortality within 30 days postoperatively, length of ICU stays and postoperative hospital stays, and cost of hospitalization. Patients were divided into the SSI group and non-SSI group based on the occurrence of SSI. Multivariable logistic regression was performed to analyze risk factors of SSI after colorectal surgery, and subgroup analysis was conducted for open and laparoscopic surgery. Results: The incidence of SSI after colorectal surgery was 5.6% (119/2122), including 47 cases (47/119, 39.5%) with superficial incisional infections, 24 cases (24/119, 20.2%) with deep incisional infections, and 48 cases (48/119, 40.3%) with organ/space infections. The occurrence of SSI significantly increased mortality [2.5% (3/119) vs. 0.1%(3/2003), χ2=22.400, P=0.003], the length of ICU stay [0 (1) day vs. 0(0) day, U=131 339, P<0.001], postoperative hospital stay [18.5 (12.8) days vs. 9.0 (6.0) days, U=167 902, P<0.001], and medical expenses [75 000 (49 000) yuan vs. 60 000 (31 000) yuan, U=126 189, P<0.001] (P<0.05). Multivariate analysis revealed that hypertension (OR=1.782, 95%CI: 1.173-2.709, P=0.007), preoperative albumin level (OR=1.680, 95%CI: 1.089-2.592, P=0.019), a contaminated or infected incision (OR= 1.993, 95%CI: 1.076-3.689, P=0.028), emergency surgery (OR=2.067, 95%CI: 1.076-3.972, P=0.029), open surgery (OR=2.132, 95%CI: 1.396-3.255, P<0.001), and surgical duration (OR=1.804, 95%CI: 1.188-2.740, P=0.006) were risk factors for SSI, while preoperative skin preparation (OR=0.478, 95%CI: 0.310-0.737, P=0.001) was a protective factor for SSI. Subgroup analysis was performed on patients undergoing open or laparoscopic surgery. The incidence of SSI in the open surgery group was 10.2%, which was significantly higher than that in the laparoscopic or robotic group (3.5%, χ2=39.816, P<0.001). Subgroup analysis identified that a contaminated or infected incision (OR=2.168, 95%CI: 1.042-4.510, P=0.038) and surgical duration (OR=2.072, 95%CI: 1.171-3.664, P=0.012) were risk factors for SSI after open surgery, while mechanical bowel preparation (OR=0.428, 95%CI: 0.227-0.807, P=0.009) and preoperative skin preparation (OR=0.356, 95%CI: 0.199-0.634, P<0.001) were protective factors for SSI after open surgery. In laparoscopic surgery, diabetes mellitus (OR= 2.292, 95%CI: 1.138-4.617, P=0.020) and hypertension (OR=2.265, 95%CI: 1.234-4.159, P=0.008) were risk factors for SSI. Conclusions: The incidence of SSI after colorectal surgery is 5.6%. Minimally invasive surgery should be selected to reduce the occurrence of postoperative SSI. To prevent the occurrence of SSI after open surgery, skin preparation and mechanical bowel preparation should be performed before the operation, and the duration of the operation should be shortened as much as possible. In the perioperative period, care of patients with hypertension, diabetes, and contaminated or infected incisions should be given particular attention.

[Surgical site infection after abdominal surgery in China: a multicenter cross-sectional study].

Objective: Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery. Methods: A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery. Results: A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ(2)=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ(2)=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions: The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

[Risk factors for surgical site infection after emergency abdominal surgery: a multicenter cross-sectional study in China].

Objective: Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence. Methods: Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS. Results: A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ(2)=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ(2)=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ(2)=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ(2)=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ(2)=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ(2)=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ(2)=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions: For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.

TGF-beta: a fibrotic factor in wound scarring and a potential target for anti-scarring gene therapy.

Hypertrophic scar and keloid are common and difficult to treat diseases in plastic surgery. Results of wound healing research over the past decades have demonstrated that transforming growth factor-beta (TGF-beta) plays an essential role in cutaneous scar formation. In contrast, fetal wounds, which heal without scarring, contain a lower level of TGF-beta than adult wounds. How to translate the discovery of basic scientific research into the clinical treatment of wound scarring has become an important issue to both clinicians and basic researchers. The development of gene therapy techniques offers the potential to genetically modify adult wound healing to a healing process similar to fetal wounds, and thus reduces wound scarring. This article intends to review the roles of TGF-beta in the formation of wound scarring, the possible strategies of antagonizing wound TGF-beta, and our preliminary results of scar gene therapy, which show that wound scarring can be significantly reduced by targeting wound TGF-beta.

[Histopathological and ultrastructural changes in 57 cases of high altitude heart disease].

This paper reports the histopathologic and ultrastructural changes in 37 children and 20 adults with high altitude heart disease. Its clinicopathologic features, diagnostic criteria and differential diagnosis from Ke-shan disease and other heart diseases are discussed. The right heart of 37 children showed hypertrophy and dilatation. Microscopically, necrosis and scarring were found mainly in the right ventricular wall (29/37) and the anterior papillary muscles (29/37) of the right ventricle. The hearts of 20 adults (19 Hans and 1 Tibetan) were enlarged and increased in weight. Heart weight increased to 400-500g in 15 cases, and hypertrophy of both ventricles was seen in 16 cases. Necrosis and scarring were found mainly in the papillary muscles (20:16) and the ventricular walls (11:19) of the left and right ventricles. Electronmicroscopy showed that myofibrils were dissolved or degenerated, mitochondria swelled, endoplasmic reticula dilated and glycogen granules decreased. As regards the pathogenesis, the authors stress the role of chronic hypoxia which causes myocardial damage, and advocate the importance of early diagnosis and treatment.

Leukemia X fibroblast hybrid cells prolong the lives of leukemic mice.

ASL-1 leukemia X LM(TK-) fibroblast hybrid cells prolong the livers of leukemic (A/JXC3H/HeJ)F1 mice. The hybrid cells, like the fibroblast cells used in forming the hybrid, have lost malignant growth properties in immunocompetent recipients and are rejected. Mice receiving hybrid cells along with ASL-1 cells exhibit immunity toward the leukemia cells; approximately 50% of the animals injected with 10(6) or more hybrid cells along with ASL-1 cells survive more than 60 days; animals in the control group injected with leukemia cells alone invariably die in shorter intervals. The immunity generated is persistent for at least 6 months. Some leukemic mice receiving doses of combination chemotherapy which are insufficient to cure them of the disease survive for prolonged and at times indefinite periods if they are injected with hybrid cells. The immunity generated in mice receiving hybrid cells is directed toward a leukemia-associated antigen of leukemia cells expressed by hybrid cells as well. In mixed lymphocyte culture a heightened stimulation of spleen cells from hybrid cell-injected mice toward ASL-1 cells is observed.

Surface antigens of immunoprotective leukaemia x fibroblast hybrid cells which have lost malignant properties in histocompatible mice differ from the malignant parental cells.

Somatic hybrids of ASL-1 leukaemia cells and LM(TK-) fibroblast cells, established mouse cell lines, are rejected by immunocompetent histocompatible mice; however, they grow progressively in nude mice and proliferate indefinitely in vitro. Mice rejecting such hybrid cells exhibit immunity toward ASL-1 leukaemia cells, used as one of the parents in forming the hybrid. In histocompatible recipients, ASL-1 cells are highly malignant, but LM(TK-) cells are rejected. Several distinguishing characteristics in the properties of the surface antigens of the three cell types are described. ASL-1 cells and hybrid cells but not LM(TK-) cells form an antigenically cross-reactive leukaemia-associated antigen; however, it is not detected on the surface membranes of ASL-1 cells taken directly from leukaemic mice. The antigen becomes apparent after short-term culture of the cells. Serum from leukaemic animals, unlike specific antibodies, has no effect upon the expression of the leukaemia-associated antigen of either hybrid or ASL-1 cells. Hybrid cells form a 'second' antigen, foreign to F1 mice, which can be distinguished from the leukaemia-associated antigen of ASL-1 cells. It is not detected on either parental cell. The leukaemia-associated antigen of ASL-1 cells is more readily digested by each of three proteases used than the analogous antigen of hybrid cells. The heightened immunogenic properties of hybrid cells is reflected by the observation that spleen cells from mice injected with hybrid cells undergo extensive proliferation in short-term in vitro culture, with or without an added specific stimulus.

Modulation of ocular hydrodynamics and iris function by bremazocine, a kappa opioid receptor agonist.

This study was designed to determine the activity of bremazocine (BRE), a relatively selective kappa opioid receptor agonist, on intraocular pressure (IOP), aqueous humor formation and pupil diameter (PD) in conscious, normal, dark-adapted New Zealand white (NZW) rabbits. IOP was measured in normal and unilaterally sympathectomized rabbits using a calibrated pneumatonometer and the aqueous flow rate was determined by the use of a Fluorotron Master. A masked-design study was conducted in which the rabbits' eyes were treated with BRE topically and unilaterally; the fellow eyes received vehicle. IOP and PD measurements were taken at 0.5 hr and 0 time before BRE and 0.5, 1, 2, 3, 4 and 5 hr post-treatment. Fluorophotometry recordings were taken at 1 hr before and 0.5, 1.5, 2.5 and 3.5 hr after topical application of the drug or vehicle. The effect of the relatively selective kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), on bremazocine-induced changes in IOP, PD and aqueous flow was also determined. BRE (10 and 100 micrograms 25 microliters-1 vehicle) produced dose-related, bilateral reductions in IOP, PD and aqueous humor flow. A large increase in IOP (14 mmHg) was observed when BRE (100 micrograms) was applied to sympathectomized eyes. This ocular hypertensive effect was antagonized when the sympathectomized eyes were pretreated with naloxone (200 micrograms), a non-selective opioid receptor antagonist. BRE (10 and 100 micrograms) decreased the aqueous humor flow rate bilaterally by approximately 48 and 60%, respectively, at 0.5 hr after administration to the ipsilateral eye. Nor-BNI (100 micrograms) antagonized the effect of BRE (10 micrograms) on IOP and aqueous flow rates more effectively than on PD. These data indicate that bremazocine causes reductions in IOP by suppressing aqueous flow, but the ocular hypotensive effects are dependent on the presence of intact sympathetic nerves. Antagonism of BRE's effects on aqueous humor dynamics by nor-BNI suggests that the mechanism of IOP and aqueous flow reduction may involve, in part, an action on kappa receptors. Further experiments are necessary to fully define the opioid receptor populations in the ciliary body.

[Development and application of hybridoma secreting monoclonal antibody against poly-human serum albumin].

Two hybridomas which secrete monoclonal antibody (McAb) against polymerized human serum albumin (PHSA) were obtained by the fusion of SP2/0 myeloma cell with immune murine spleen cells. One of the McAb was identified as mouse IgG1, the other was IgM. The titers of these purified McAb was 1:16 364 with passive hemagglutination assay (PHA). After labelling with 125I by chloramine-T method, a solid phase radioimmune assay for detecting the PHSA has yielded in 21 positive results, out of 126 HBsAg positive sera, but 53 HBsAg negative sera were all negative. At present we have not seen any report of PHSA present in circulation. PHSA may be as a bridge bind receptor between HBV and hepatocytes and then initiate infection. The appearance of PHSA in HBsAg positive sera could be the result of the damage of the liver during virus infection. More work should be done for this explanation.