[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Application of Bi's intestinal loop binding in treating patients with critical esophagojejunal anastomosis leakage].

Objective: To assess the safety and feasibility of Bi's intestinal loop binding treatment of esophageal jejunal anastomotic leak after total gastrectomy. Methods: Bi's Intestinal loop binding are suitable for patients who underwent radical total gastrectomy+Roux-en-Y anastomosis and were confirmed by upper gastrointestinal angiography to have esophageal jejunal anastomotic leakage and whose conservative or endoscopic treatment was ineffective. The operation procedure is as follows: take the original central incision of the upper abdomen, remove the abscess around the anastomoses after ventral incision, and place drainage tube inside the abscess, which is convenient to rinse and drain after operation. A double 1-0 VICRYL is applied to the loop of gastrointestinal surrogate 10-15 cm proximal to the jejuno-jejunal anastomosis. The knot tension is tight to prevent regurgitation of digestive juices, but too much force should be avoided to cut the intestinal tract. Nutritional jejunostomy fistula was performed at 10‒15 cm distal to the jejuno-jejunal anastomosis and gastric tube was retained during the operation. The preoperative and postoperative data from 12 patients with jejunal esophageal anastomotic leak after total radical gastrectomy and Roux-en-Y anastomosis were retrospectively analyzed from October 2016 to January 2023 in gastrointestinal surgery and pancreas surgery at Shanxi People's Hospital, and observed the curative effect. Results: 12 patients were managed with Bi's Intestinal loop binding, operative time (60.0±20.8) minutes, median bleeding (50±10.8) ml, median hospital stay 20(12~28) days, and median reviewing upper and mid Gastrointestinal Contrast time postoperatively 61(52~74) days. The results showed that the anastomoses healed well, all the small intestine showed good imaging, the binding wire fell off by itself, and two patients had incision infection. Conclusions: It is safe and feasible for patients with esophageal jejunostomy fistulae after total gastrectomy to use the method of Bi's Intestinal loop binding.

Helix B surface peptide protects against acute lung injury through reducing oxidative stress and endoplasmic reticulum stress via activation of Nrf2/HO-1 signaling pathway.

OBJECTIVE: Acute lung injury (ALI) is a clinical problem with poor prognosis and high mortality. The purpose of this study was to explore the effects of helix B position peptide (HBSP) on ALI and its mechanism. MATERIALS AND METHODS: C57/BL6 male mice were used to construct ALI models by LPS tracheal injection and detect the effect of HBSP on mouse ALI by subcutaneously injecting HBSP. In addition, normal human lung epithelial cell line (BEAS-2B) were cultured and stimulated with HBSP. Then, the effects of HBSP on oxidative stress and endoplasmic reticulum stress (ERS) in BEAS-2B cells were examined. Finally, the effect of HBSP on the Nrf2/HO-1 signaling pathway was examined, and the mechanism of action of HBSP was verified using the Nrf2/HO-1 signaling pathway inhibitor ML385. RESULTS: In vitro, HBSP increased the expression of SOD1/2 and decreased the expression of ERS-related molecules such as CHOP, GRP-78, and caspase-12, indicating that HBSP effectively reduces the level of oxidative stress and ERS in BEAS-2B cells. In addition, HBSP also increased the activity of the Nrf2/HO-1 signaling pathway and ML385 reduced the protective effect of HBSP on BEAS-2B cells. In vivo, HBSP significantly reduced LPS-induced mouse ALI. W/D and inflammatory factors in the BALF of the mouse lung were significantly reduced and the level of oxidative stress was also reduced. CONCLUSIONS: HBSP plays an important role in relieving ALI by activating Nrf2/HO-1 signaling pathway, which reduces the level of inflammation in lung tissue and oxidative stress and ERS in lung epithelial cells.

[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.

Combined CD4+ Th1 effect and lymphotactin transgene expression enhance CD8+ Tc1 tumor localization and therapy.

Type 1 T cells are the major components in antitumor immunity. The lack of efficient CD8(+) cytotoxic T (Tc) cell infiltration of tumors is a major obstacle to adoptive Tc-cell therapy. We have previously demonstrated that adenovirus (AdV)-mediated transgene lymphotactin (Lptn) expression by intratumoral AdVLptn injection and intravenous CD4(+) helper T (Th) cell transfer can enhance Tc-cell tumor infiltration and eradication of early stage tumors (5 mm in diameter). In this study, we generated ovalbumin (OVA)-specific Tc1 and Th1 cells in vitro by incubation of OVA-pulsed dendritic cells with naive T cells from T-cell receptor (TCR) transgenic OT I and OT II mice. We then investigated the potential synergy of Th1 help effect and Lptn transgene expression in Tc1-cell therapy of well-established OVA-expressing EG7 solid tumors (7 mm in diameter). Our data showed that a combined adoptive T-cell therapy of Th1 (2.5 x 10(6) cells per mouse) and Tc1 (5 x 10(6) cells per mouse) resulted in regression of all eight (100%) transgene Lptn expressed EG7 tumors, which is significantly higher than four from eight (50%) in AdVLptn/Tc1 group and two from eight (25%) in Tc1/Th1 group (P < 0.05). The amount of transferred Tc1 cells detected in Lptn-expressed tumors with Th1 treatment is 0.72%, which is significantly higher than those of AdVLptn (0.22%), Th1 (0.41%) and the control AdVpLpA (0.09%) treatment groups (P < 0.05). Enhanced Tc1 tumor localization may be derived from the chemotactic effect of Lptn and the proliferative effect of Th1 and Lptn. This novel therapeutic strategy with enhancement of Tc1 tumor localization in the therapy of well-established tumors may become a tool of considerable conceptual interest in the implementation of future clinical objectives.