Objective:To investigate the function of gasdermin D (GSDMD) in intestinal damage of mice with severe acute pancreatitis (SAP).Methods:The healthy C57BL/6 mice were divided into four groups randomly, including normal saline (NS) group, small interfering RNA (siRNA)-NS group, SAP model group and siRNA-SAP group, with 6 mice in each group. The SAP mouse model was reproduced by intraperitoneal injection of caerulein 50 μg/kg combined with lipopolysaccharide (LPS) 10 mg/kg; the NS group was given the same amount of NS; in the siRNA-SAP group and siRNA-NS group, siRNA 50 mg/kg was injected through the tail vein three times before modeling or injection of NS. The blood of mice eyeball in each group was taken 12 hours after modeling, and serum interleukins (IL-1β, IL-18) levels were detected by enzyme linked immunosorbent assay (ELISA). The mice were sacrificed to observe the general changes in abdominal cavity, the pancreas and ileum tissues were taken to observe the pathological changes under a light microscope. The expression of long-chain non-coding RNA uc.173 (lnc uc.173) was detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to detect the expression of tight junction proteins zonula occluden-1 (ZO-1) and Occludin in intestinal mucosal epithelial cells. Western blotting was used to detect the GSDMD protein expression level in the intestinal tissue.Results:The serum levels of IL-1β and IL-18 in the SAP model group were significantly higher than those in the NS group and the siRNA-NS group [IL-1β (ng/L): 146.66±1.40 vs. 44.48±5.76, 81.49±10.75, IL-18 (ng/L): 950.47±177.09 vs. 115.43±16.40, 84.84±21.90, all P < 0.05]; and the levels of IL-1β and IL-18 in the siRNA-SAP group were significantly lower than those in the SAP model group [IL-1β (ng/L): 116.26±15.54 vs. 146.66±1.40, IL-18 (ng/L): 689.96±126.08 vs. 950.47±177.09, both P < 0.05]. General observation showed that there were no obvious abnormalities in the abdominal cavity of the mice in the NS and siRNA-NS groups; the mice in the SAP model group and the siRNA-SAP group had different degrees of edema and congestion in the intestine; compared with the SAP model group, the abnormalities in the siRNA-SAP group was significantly reduced. Under light microscope, there were no obvious changes in the pancreas and intestinal mucosa in the NS group and the siRNA-NS group; the pancreatic tissue of the SAP model group and the siRNA-SAP group had different degrees of edema, inflammatory cell infiltration, and lobular structure damage, and the intestinal mucosa was damaged to a certain degree, and the villi were broken to varying degrees, but the damage in the siRNA-SAP group was lighter. The results of RT-PCR showed that the expression of lnc uc.173 in the intestinal tissues of the model SAP group was significantly lower than that of the NS group and the siRNA-NS group (2 -ΔΔCt: 0.26±0.12 vs. 1.01±0.37, 0.67±0.32, both P < 0.05), while the expression of lnc uc.173 in the siRNA-SAP group was significantly higher than that in the SAP model group (2 -ΔΔCt: 0.60±0.39 vs. 0.26±0.12, P < 0.05). Immunohistochemistry showed that ZO-1 and Occludin proteins in the NS group were distributed along the epithelial cells of the intestinal mucosa, showing a strong expression; ZO-1 and Occludin expressions were significantly reduced in the SAP model group and siRNA-SAP group, but the expressions in the siRNA-SAP group was higher than that in the SAP model group. Western blotting showed that the expression level of GSDMD protein in the intestinal tissues of the SAP model group was significantly higher than that of the NS group and the siRNA-NS group [GSDMD protein (GSDMD-N/β-actin): 1.99±0.46 vs. 1, 1.00±0.78, both P < 0.05]. Compared with the SAP model group, the expression of GSDMD protein in the siRNA-SAP group was significantly decreased [GSDMD protein (GSDMD-N/β-actin): 1.42±0.42 vs. 1.99±0.46, P < 0.05]. Conclusions:The systemic inflammatory response and intestinal mucosal barrier damage of SAP mice may be related to the increase of GSDMD expression in intestinal tissues. GSDMD mediates cell pyrolysis to promote the release of inflammatory factors, cause intestinal injury, and down-regulate the expression of intestinal epithelial cell tight junction proteins such as ZO-1 and Occludin, resulting in intestinal mucosal damage.

Objective To discuss the surgery methods and clinical curative effect of application of nickel titanium memory alloy embracing device fixed femoral fractures inside wall of bone block.Methods The clinical data of 27 patients on the application of nickel titanium memory alloy embracing device fixed femoral fractures inside wall with bone block were retrospectively analyzed.There were 9 cases of male and 18 cases offemale.They were 69 ~89 years old,average 76.2 years.And there were 19 cases on the left side of inside wall and 8 cases on the right side. Curative effect evaluation was conducted according to the Evans-Jensen norm and the improved Harris standard. Results Postoperative follow-up loss in 2 cases,and 24 cases received follow-up for 6 ~20 months,which had an average of 14.15 months and follow-up rate was 92.3%.Three cases died respectively because of acute heart failure, cerebral hemorrhage and cor pulmonale.Patients at the time of the last follow-up had Harris mean score(80 ~97), including the optimal 19 cases,fine 4 cases and poor in 1 case,and the excellent rate was 95.8%.Conclusion Sur-gery method of nickel titanium memory alloy embracing device fixed femoral fractures inside wall of bone has reliable fixation,and can restore the biomechanical balance and decrease complications,etc.It allows early functional exercise of hip part in load conditions to obtain ideal therapeutic effect.

Objective:To explore the influence of acupoint catgut embedding combined with Xuezhikang capsule on lipid metabolism and antioxidation effect in patients with statin intolerance and hyperlipidemia of spleen-kidney yang deficiency syndrome.Methods:Randomized controlled trial. A total of 82 patients with statin intolerance and hyperlipidemia who were treated in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai Puto Area Central Hospital, and Lingyun community health Service center, Xuhui District from July 2020 to June 2022 were selected and randomly divided into two groups with 41 patients in each group by odd-even ball method. The two groups were given diet and exercise guidance, and the control group was given Xuezhikang capsule orally on this basis, and the observation group was given poly(l-lactide-co-glycolide) (PLGA) thread acupoint catgut embedding on the basis of the control group. Both groups were treated continuously for 3 months. The TCM syndromes were scored before and after treatment, and body weight (BW), waist circumference (WC) and body mass index (BMI) were recorded. The levels of TC, TG, HDL-C and LDL-C were detected by fully automatic biochemical analyzer. The levels of serum SOD, GSH-Px and total antioxidant capacity (TAOP) were measured by ELISA. The level of serum endothelin-1 (ET-1) was assessed by radioimmunoassay. Color Doppler ultrasound diagnostic instrument was used to detect the brachial artery flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD).Results:The scores of chilly sensation and cold limbs [(1.27±0.12) vs. (1.46±0.16), t=6.08], loose stool [(1.41±0.16) vs. (1.63±0.18), t=5.85], fatigue [(1.45±0.15) vs. (1.57±0.17), t=3.39], dizziness [(1.15±0.11) vs. (1.26±0.13), t=4.14] and loss of appetite [(1.21±0.13) vs. (1.39±0.15), t=5.81] in observation group after treatment were significantly lower than those in the control group ( P<0.01). BW [(68.03±6.57)kg vs. (71.55±6.76)kg, t=2.39], WC [(85.13±4.63)cm vs. (87.35±4.85)cm, t=2.12] and BMI [(27.35±2.84)kg/m 2vs. (29.18±3.05)kg/m 2, t=2.81]were lower than those in the control group ( P<0.05). The levels of serum TC [(3.15±0.13)mmol/L vs. (3.38±0.17)mmol/L, t=6.88], TG [(1.98±0.11)mmol/L vs. (2.21±0.15)mmol/L, t=7.92]and LDL-C [(2.46±0.26)mmol/L vs. (3.04±0.33)mmol/L, t=8.84]were significantly lower compared with those in control group ( P<0.01) while the level of HDL-C [(1.88±0.24)mmol/L vs. (1.74±0.21)mmol/L, t=2.81]was higher than that of the control group ( P<0.01). The levels of serum SOD [(57.82±5.84)μg/L vs. (55.06±5.61)μg/L, t=2.18], GSH-Px [(96.51±9.52)U/L vs. (92.26±9.25)U/L, t=2.30]and TAOP [(6.21±0.57)U/L vs. (5.94±0.54)U/L, t=2.20]were significantly higher compared to control group ( P<0.05). Serum ET-1 [(60.43±4.36) pg/L vs. (63.71±4.68) pg/L, t=3.28] level was significantly lower than that in control group ( P<0.01), while FMD [(12.48±1.02)% vs. (11.34±0.95)%, t=5.24] and NMD [(15.12±1.24)% vs. (14.44±1.18)%, t=2.54] were significantly higher than those in control group ( P<0.01). Conclusion:The combination of acupoint catgut embedding and Xuezhikang capsule can reduce the scores of TCM syndromes, lower the obesity and blood lipids, enhance the antioxidant function and improve the vascular endothelial function in patients with statin intolerance and hyperlipidemia.

Objective:To investigate the effects of poly (ADP-ribose) polymerase-1(PARP-1) in intestinal mucosal barrier injury in rat model with severe acute pancreatitis (SAP).Methods:Twenty healthy male Wistar rats were divided into four groups ( n=5 each group) using a random table method: control, SAP, 3-aminobenzamide (3-AB), and 3-AB control groups. The SAP model was induced by intraperitoneal injection of cerulean with lipopolysaccharide. At 30 min, the rats were treated with the PARP-1 inhibitor, 3-AB, or normal saline,separately. After 12 h, all rats were sacrificed to harvest pancreas tissues, intestines tissues, and blood from the hearts for index detection. Serum amylase (AMY) and interleukin (IL)-6 levels were measured using an automatic biochemical instrument and enzyme-linked immunosorbent assay (ELISA), respectively.The protein expression of PARP-1 and nuclear factor (NF-κB) were measured using Western blot and that of occludin was measured using an immunohistochemical test. One-way analysis of variance was used for comparison of multiple groups of variables. Non-parametric tests of rank conversion were used when variances were not uniform. A P <0.05 was considered statistically significant. Results:Compared to the control group, the following indexes in the SAP group were significantly increased: ascites (with serious hemorrhage and necrosis in the pancreas and disordered intestinal villi),serum AMY and IL-6 levels, and the expression of PARP-1 and NF-κB. However, Occludin expression was significantly decreased. There was no significant difference between 3-AB group and 3-AB control group. Compared to the SAP group, the severity of SAP and pancreatitis-associated intestinal injury was significantly attenuated with the administration of 3-AB. Serum AMY and IL-6 levels were significantly decreased (serum AMY: 1 879.25 ± 736.6 U/L vs 5 569.33 ± 1993.48 U/L; IL-6: 77.98 ± 20.65 pg/mL vs 209.14 ± 79.08 pg/mL, both P<0.05), but the expression of PARP-1 and NF-κB were significantly increased (PARP-1: 1.44 ± 0.09 vs 1.49 ± 0.13; NF-κB: 0.63 ± 0.09 vs 0.96±0.08, both P<0.05). Similarly, Occludin expression was significantly decreased (6.7±1.5 vs 3.2±1.1, P<0.05). Conclusions:Inhibition of PARP-1 has protective effects on SAP associated intestinal mucosal barrier damage. The mechanism may be related to the inhibition of NF-κB signaling pathway and increase intestinal mucosal Occludin protein expression.

Serum cholinesterase （ChE） level is important for the diagnosis and prognostic evaluation of various diseases such as liver diseases and toxic diseases， and butyrylcholinesterase （BuChE） is an important component of ChE. Mutations in the BCHE gene can cause a significant reduction in the level of BuChE， with extensive reports in European and American populations and relatively few reports in Eastern countries， particularly China. This study describes a male patient， aged 35 years， who was misdiagnosed with organophosphorus pesticide poisoning due to an extreme reduction in ChE level and was given detoxification therapy， but such diagnosis was excluded by various biochemical examinations. Finally whole-exome sequencing and Sanger sequencing revealed the complex heterozygous mutations of c.1027dup and c.401dup at exon 2 of the BCHE gene， and hereditary BuChE deficiency due to these mutations is the cause of the extreme reduction in ChE level.