Prospective comparison of two surgical approaches for incarcerated and strangulated inguinal hernia: preperitoneal hernioplasty through the lower abdominal median incision and laparoscope (TAPP).

The optimal surgical approach of incarcerated and strangulated inguinal hernia is controversial. Retrospective studies showed that surgical approaches through lower abdominal median incision or laparoscopic are superior to the oblique inguinal incision, respectively. Whether transabdominal laparoscopic approach is superior to the lower abdominal median incision approach needs prospective research.Prospective comparative study of patients with incarcerated and strangulated groin hernia admitted to Jinshan hospital for emergency surgery from January 2018 to June 2022. They were divided into two groups according to different surgical approach. The open preperitoneal repair group (OPR) was operated through the lower abdominal median incision. Laparoscopic preperitoneal repair group (TAPP) was completed under transabdominal laparoscope. The perioperative complications and long-term results of the two groups were compared and analyzed. Eighty-two patients met the inclusion criteria, 40 in OPR group and 42 in TAPP group. Baseline data of the two groups were comparable. Thirteen cases (15.9%) of the two groups underwent intestinal resection and anastomosis. Seventy cases (90.2%) underwent the 1st stage mesh repair, including 5 cases of preperitoneal hernioplasty after intestinal resection. The average operation time of TAPP group was 13 min longer (60.7 ± 13.7 min vs 47.8 ± 19.8 min P < 0.001), and the visual analogue scale pain score at 24 h after operation was lower (3.5 ± 1.2 vs 4.4 ± 1.7 P = 0.019) than that of OPR group. There was 1 case of bladder injury (2.5%) in OPR group and 1 case of inferior abdominal artery injury (2.4%) in TAPP group. There was no difference in the rate of the 1st stage hernioplasty between the two groups. In OPR group, 2 cases (5%) extended the incision for more than 2 cm, while in TAPP group, 1 case (2.4%) converted to laparotomy. The time of hospital stay (3.2 ± 1.8 d vs 4.3 ± 2.7 d, P = 0.036) and return to normal activities (7.9 ± 2.7 d vs 11.0 ± 4.4 d, P < 0.001) were shorter in TAPP group. The rate of total postoperative complications including chronic pain, surgical-site infection, seroma, hernia recurrence and so on was 11.9% in TAPP group, which was not significantly different from 25% in OPR group (P = 0.212). There were no cases of mesh related infection and death within 30 days in both groups.TAPP is safe and feasible for the operation of acute incarcerated inguinal hernia. TAPP had better comfort and faster recovery over open preperitoneal repair for the appropriate patients with incarcerated/strangulated inguinal hernia, which can reduce acute pain, shorten hospital stay and return to normal activities earlier.

Rapid generation of a mouse model for evaluating on-target normal tissue toxicity of human CAR-T cells using replication-defective recombinant adenovirus.

INTRODUCTION: The on-target off-tumor toxicity of chimeric antigen receptor-engineered T cells (CAR-T) might lead to fatal side effects in cancer patients, which remains as a major obstacle to the clinical application of CAR-T immunotherapy. The off-tumor on-target normal tissue toxicity of CAR-T cells needs to be evaluated in preclinical studies using rational animal models. OBJECTIVES: We aim to develop a rational animal model for assessing the off-tumor on-target normal tissue toxicity of various CAR-T cell designs quickly. METHODS: We used a recombinant adenovirus type 5 carrying human HER2/ERBB2 (Ad5-HER2) or CD47 gene (Ad5-CD47) to rapidly generate a mouse model with tunable human antigen expression on normal liver tissue to determine immunotoxicity of traditional CAR-T and hypoxia-response CAR-T cells in vivo. RESULTS: The obvious liver damage and lymphocyte infiltration were not observed in mice with human antigen-high livers 8 days post-infection. Interestingly, the lethal liver damage, systemic cytokine release and CAR-T cells infiltration in liver were only observed in mice that received traditional CAR-T cells, but not in hypoxia-response CAR-T cells. CONCLUSION: Adenovirus-based expression of target antigen in normal mouse tissue may be a useful method for assessing on-target CAR-T cell toxicity in normal tissues, especially various CAR-T cell designs that have the potency of conditional regulation in tumor microenvironment (TME).

Computed Tomography Perfusion Imaging Detection of Microcirculatory Dysfunction in Small Intestinal Ischemia-Reperfusion Injury in a Porcine Model.

OBJECTIVE: To evaluate multi-slice computed tomography (CT) perfusion imaging (CTPI) for identifying microcirculatory dysfunction in small intestinal ischemia-reperfusion (IR) injury in a porcine model. MATERIALS AND METHODS: Fifty-two pigs were randomly divided into 4 groups: (1) the IR group (n = 24), where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA) for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively); (2) the sham-operated (SO) group (n = 20), where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively); (3) the ischemia group (n = 4), where the SMA was separated and clamped for 2 h, without reperfusion, and (4) baseline group (n = 4), an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) and for histopathological examination. RESULTS: The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia). The blood flow (BF), blood volume (BV), and permeability surface (PS) among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion. CONCLUSION: CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury.

Astragalus polysaccharide induces the apoptosis of human hepatocellular carcinoma cells by decreasing the expression of Notch1.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer death worldwide. Astragalus polysaccharide (APS), the primary active component extracted from a traditional Chinese medicinal herb Astragalus membranaceus, has been proved to exert a marked inhibitory effect on a number of types of human solid tumors. In the present study, we aimed to examine the effects of APS on the survival of the HCC cell line H22 and to elucidate the underlying regulatory mechanisms responsible for these effects. Our results revealed that the mRNA and protein expression of Notch1 was significantly upregulated in the HCC tissues compared with that in the normal tissues. APS decreased cell viability and induced the apoptosis of HCC cells in a concentration-dependent manner, which were evaluated using a cell counting kit-8 (CCK-8) assay and flow cytometric analysis, respectively. Furthermore, APS regulated the expression of apoptosis-related genes (Bcl-2 and BAX) and proteases (caspase-3 and -8). Mechanically, Notch1 expression was found to be suppressed in HCC cells, and further analysis indicated that Notch1 knockdown by siRNA significantly reduced cell viability, suppressed the metastatic capacity and enhanced the apoptosis of HCC cells. Taken together, these findings suggest that Notch1 may be a potential therapeutic target for the treatment of HCC.