Enhanced recovery after surgery in congenital duodenal obstruction.

BACKGROUND: The present study aims to explore the clinical application of enhanced recovery after surgery (ERAS) in pediatric patients with congenital upper gastrointestinal obstruction (CUGIO). METHODS: A total of 82 pediatric patients with CUGIO admitted to the neonatal intensive care unit in Kunming Children's Hospital between June 2017 and June 2021 were enrolled in the present study and divided into two groups: the ERAS group (n = 46) and the control group (n = 36). The ERAS management mode was adopted in the ERAS group, and the conventional perioperative management mode was adopted in the control group. RESULTS: In the ERAS group and the control group, the time to the first postoperative bowel movement was 49.2 ± 16.6 h and 58.4 ± 18.8 h, respectively, and the time to the first postoperative feeding was 79 ± 7.1 h and 125.2 ± 8.3 h, respectively. The differences in the above two indicators between the two groups were statistically significant (P < 0.05). In the ERAS group, the days of parenteral nutrition and the length of hospital stay were 14.5 ± 2.3 d and 18.8 ± 6.4 d, respectively. In the control group, 17.6 ± 2.2 d and 23.1 ± 8.1 d, respectively. The differences in these two indicators between the two groups were statistically significant (P < 0.05). CONCLUSION: The ERAS management model had a positive effect on early postoperative recovery in pediatric patients with CUGIO.

Management of a Complex Peristomal Fistula: A Case Study.

BACKGROUND: We describe our experiences caring for a patient with a peristomal fistula (PF), characterized by suppuration from a peristomal abscess. The challenges associated with this case included management of a complex fistula and prevention of abdominal necrotizing fasciitis and peritonitis. CASE: A 63-year-old man presented with severe peristomal swelling and pain resulting from an abscess adjacent to his ileostomy. He was malnourished and depressed. He underwent a low anterior resection (Dixon procedure) for rectal cancer 2 years ago and an abdominoperineal resection (Miles procedure) for the recurrence of rectal carcinoma 1 year later. In addition, he underwent bowel resection with the creation of an ileostomy due to intestinal obstruction caused by a second recurrence approximately 1 month prior to this admission. Following evaluation of the fistula anatomy, incision and drainage of the abscess was performed. Diversion of the effluent was used to control infection and promote fistula closure. A registered dietitian and a psychologist were consulted to optimize nutrition and treat his depression. After 20 days of treatment, the patient recovered and was safely discharged. CONCLUSION: Peristomal fistula management should include anatomical assessment, incision and drainage of the abscess, diversion to control effluent, and skin protection. For complex cases, the coordinated efforts of the interdisciplinary team are imperative.

Estrogen is an important mediator of mast cell activation in ovarian endometriomas.

Endometriosis is an estrogen-dependent disease. Previous research has shown that abnormal enzymes associated with estrogen (E2) metabolism and an increased number of mast cells (MCs) in endometriomas are implicated in the pathogenesis of endometriosis. However, it remains unclear how MCs mediate the role of E2 in endometriosis. Accordingly, we investigated whether E2 was associated with the number of MCs, and the rate of degranulation, in local ovarian endometriomas, as well as the role of E2 on MCs during the pathogenesis of endometriosis. Using enzyme-linked immunosorbent assay and immunohistochemistry, we found that concentrations of E2, and the number and activity of MCs, were significantly higher in ovarian endometriomas than in controls, and that these parameters were correlated with the severity of endometriosis-associated dysmenorrhea. By measuring the release of hexosaminidase, we found that the rate of RBL2H3 cell degranulation increased after E2 treatment. Furthermore, activation of RBL2H3 cells by E2 was found to trigger the release of biologically active nerve growth factor, which promotes neurite outgrowth in PC12 cells and also sensitizes dorsal root ganglion cells via upregulation of Nav1.8 and transient receptor potential cation channel (subfamily V member 1) expression levels. When treated with E2, endometriotic cells could promote RBL2H3 cell recruitment by upregulating expression levels of stem cell factor, transforming growth factor-ß and monocyte chemoattractant protein-1; these observations were not evident with control endometrial cells. Thus, elevated E2 concentrations may be a key factor for degranulation and recruitment of MCs in ovarian endometriomas, which play a key role in endometriosis-associated dysmenorrhea.

Endoplasmic reticulum stress is involved in the connection between inflammation and autophagy in type 2 diabetes.

Type 2 diabetes is a chronic inflammatory disease. A number of studies have clearly demonstrated that cytokines such as interleukin 1ß (IL1ß) contribute to pancreatic inflammation, leading to impaired glucose homeostasis and diabetic disease. There are findings which suggest that islet ß-cells can secrete cytokines and cause inflammatory responses. In this process, thioredoxin-interacting protein (TXNIP) is induced by endoplasmic reticulum (ER) stress, which further demonstrates a potential role for ER stress in innate immunity via activation of the NOD-like receptor (NLRP) 3/caspase1 inflammasome and in diabetes pathogenesis via the release of cytokines. Recent developments have also revealed a crucial role for the autophagy pathway during ER stress and inflammation. Autophagy is an intracellular catabolic system that not only plays a crucial role in maintaining the normal islet architecture and intracellular insulin content but also represents a form of programmed cell death. In this review, we focus on the roles of autophagy, inflammation, and ER stress in type 2 diabetes but, above all, on the connections among these factors.

[Role of mast cells in estrogen-mediated experimental endometriosis in rats].

OBJECTIVE: To investigate the role of mast cells in the pathogenesis of estrogen-mediated experimental endometriosis in rats. METHODS: Endometriosis model was established by transplanting autologous fragments of uterus to the inner surface of the abdominal wall in 24 un-pregnant female Sprague Dawley rats. The rats were divided randomly into three groups (n=8 in each group), and were injected with different doses of estrogen: high-dose group (200 µg·kg⁻¹·d⁻¹), low-dose group (100 µg·kg⁻¹·d⁻¹) and the control group (0 µg·kg⁻¹·d⁻¹). The ovaries were surgically removed in high-dose and low-dose groups. Four rats were sacrificed in each group at 2 and 4 weeks after surgery. Their serum estradiol levels, size of lesions, total number of mast cells and degranulations, serum TNF-α levels, expression of tryptase and NGF in tissues were analyzed and compared among groups. RESULTS: The mean levels of serum estradiol 2 weeks and 4 weeks after model established and serum TNF-α at 4 weeks in estrogen-treated groups were significantly higher than those in control group (all P<0.05). The mean size of endometriotic lesions in the estrogen-treated groups was also significantly larger than that in the control group 2 weeks and 4 weeks after model established (all P<0.05). Meanwhile, both at week 2 and week 4, the mean ratio of degranulation/total number of mast cells by toluidine blue staining in low-dose estrogen group was significantly higher than that in the control group (P<0.05). The expression of NGF in high-dose estrogen group was significantly higher than that in the control group at week 4(P<0.05). CONCLUSION: Estrogen can promote the growth of endometriotic lesions and may mediate the pathogenesis of endometriosis by activating mast cells, which may be associated with increasing TNF-α and NGF levels.

[Sodium cromoglycate attenuates experimental endometriosis in rats by regulating mast cells].

OBJECTIVE: To investigate the effect of sodium cromoglycate on experimental endometriosis in rats. METHODS: Endometriosis model was established in 36 unpregnant female SD rats by transplanting autologous fragments of endometrium to the inner surface of the abdominal wall. The endometriotic lesions were measured by a second laparotomy 2 weeks after surgery. Then the rats were randomly divided into four groups (n=8 in each group) to receive intraperitoneal injection of different doses of sodium cromoglycate for 2 weeks: high-dose group (20 mg·kg⁻¹·d⁻¹); low-dose group (10 mg·kg⁻¹·d⁻¹); the negative control group and the blank control group. The animals were sacrificed and the size of the lesions were measured. The endometriosis model of SD rats was identified by HE staining and immunohistochemical staining of keratin and vimentin. The total number of mast cells and their degranulation were measured by Toluidine blue staining; the concentrations of TNF-α in serum were measured by enzyme linked immunosorbent assay; the concentrations of estradiol in serum were measured by enzyme immunoassay; the expression of tryptase and nerve growth factor (NGF) were measured by immunohistochemical staining. RESULTS: The number of activated mast cells (MC) by Toluidine blue staining in high-dose group was significantly lower than that in negative control group (P<0.05), and its ratio of degranulation/total number of MC was significantly lower than that in negative control group or blank control group (P<0.05). The serum TNF-α levels and tryptase expression in tissues in high-dose group were significantly lower than those in negative control group or blank control group (P<0.05). However, no significant difference in the size of endometriotic lesions and expression of NGF was found among groups (P>0.05). CONCLUSION: Sodium cromoglycate can stabilize mast cells from degranulation, which may relieve the clinical symptoms of endometriosis by reducing TNF-α and tryptase levels.

The Effect of Kangaroo Mother Care After Duodenal Obstruction in Neonates.

Objective: The present study aimed to explore the effectiveness of clinical application of kangaroo mother care (KMC) in neonates after surgery for duodenal obstruction in achieving total enteral nutrition (TEN) and shortening the length of hospital stay. Methods: A prospective study of 60 cases of surgery for duodenal obstruction in pediatric patients in the neonatal intensive care unit of Kunming Children's Hospital between January 2018 and December 2019 was conducted. The study subjects included 15 cases with intestinal malrotation, 18 cases with circular pancreas, 10 cases with a duodenal septum, and 17 cases with duodenal atresia or duodenal stenosis. According to the single and double numbers of the operation date, the subjects were randomly divided into the control group and observation group, with 30 cases in each group. The conventional care of enhanced recovery after surgery (ERAS) was carried out in the control group, and KMC based on ERAS conventional care was implemented in the observation group. The difference in the duration to achieve TEN and the length of hospital stay between the two groups of patients after care was compared and analyzed. Results: The average duration to achieve TEN for neonates with duodenal obstruction in the control group was 14.23 ± 3.17 days, while that in the observation group was 12.27 ± 1.15 days. The average length of hospital stay in the control group was 17.22 ± 4.71 days, while that in the observation group was 13.34 ± 2.70 days. There was a significant difference in the duration to achieve TEN and the average length of hospital stay between the two groups (P < 0.05). The duration to achieve TEN and the length of hospital stay in pediatric patients were significantly shorter in the observation group than in the control group. Conclusion: Kangaroo mother care has important clinical significance and application value in shortening the duration to achieve TEN and the length of hospital stay in neonates after surgery for duodenal obstruction.

A clinical study on the tip localization of peripherally inserted central catheter (PICC) guided by intracavitary electrocardiography in newborns: a randomised trial.

BACKGROUND: The present study aimed to investigate the P-wave changes in intracavitary electrocardiography (IC-ECG) during catheterization with a peripherally inserted central catheter (PICC) in order to provide guidance for the accurate localization of the tip of the PICC. METHODS: A total of 106 newborns who needed a PICC were randomly divided into two groups-a study group and a control group-using a random number table, with 53 cases in each group. In the study group, the ECG monitor was connected after the successful puncture and insertion of the PICC into the right sternoclavicular joint, and the position of the catheter tip was determined according to the P-wave changes on the IC-ECG. Localization X-rays were taken at the same time. In the control group, after the successful routine puncture and insertion of the PICC into the location to a predetermined length, localization X-rays were taken. The accuracy, procedure duration, and cost of the two localization methods were evaluated. RESULTS: The accuracy of the localization in the study group was 92.5%, but the difference was not significant when compared with the control group (P>0.05). The duration of the procedure in the study group was 5.12±1.57 minutes, and the cost was 7.12±0.56 yuan, both of which were significantly different when compared with the control group (P<0.05). CONCLUSIONS: P-wave changes during IC-ECG have high accuracy in determining the location of the tip of the PICC. It is also a simple method and has certain clinical application value. TRIAL REGISTRATION: Chinese Clinical Trial Registry (number: ChiCTR2100047660).

XPC gene intron 11 C/A polymorphism is a predictive biomarker for the sensitivity to NP chemotherapy in patients with non-small cell lung cancer.

The fact that intron single nucleotide polymorphisms could regulate gene expression or even alter gene expression levels has been the focus of attention. To study the relationship between the intron 11 C/A single nucleotide polymorphism of XPC gene and the efficacy of vinorelbine and cisplatin (NP) chemotherapy, 164 patients with non-small cell lung cancer (NSCLC) taking NP chemotherapy drugs were evaluated according to the efficacy of the treatment. We used polymerase chain reaction restriction fragment length polymorphism to examine the C/A polymorphism in the XPC gene intron 11 of the DNA samples extracted from peripheral blood. It was found that the frequency of patients in the effective group with C/C+C/A genotype (37.6%) had significant difference to chemotherapy than that of patients with A/A homozygotes (27.7%) in the same group (P=0.043, odds ratio=2.366, 95% confidence interval=1.026-5.457). Therefore, NSCLC patients with the C/C+C/A genotype are more sensitive to NP treatment than those with the A/A genotype. The XPC gene intron 11 C/A polymorphism may be a predictive biomarker for sensitivity to NP chemotherapy in patients with NSCLC.

Role of autophagy in LPS­induced inflammation in INS­1 cells.

Inflammation has been implicated in the pathogenesis of type 2 diabetes (T2D), which is a progressive disease characterized by pancreatic ß­cell dysfunction and apoptosis with consequential insufficient insulin secretion. Autophagy is necessary to maintain the structure, mass and function of pancreatic ß­cells. The present study investigated the crosstalk between autophagy and inflammasome activation in T2D. INS­1 cells were stimulated with lipopolysaccharide. Apoptosis and reactive oxygen species (ROS) formation were measured using flow cytometry, and cell proliferation was measured using Cell Counting Kit­8 solution. Autophagy was assayed using western blotting and transmission electron microscopy. The expression levels of interleukin­1ß (IL­1ß) and caspase­1 were detected by western blotting. The results demonstrated that inhibiting autophagy using 3­methyladenine (3­MA) promoted INS­1 cell apoptosis. This response was correlated with an increase in ROS production and the inflammatory response, including IL­1ß maturation and caspase­1 activation. Furthermore, when ROS were inhibited using N­acetyl­L­cysteine, inflammation was decreased. These results demonstrated that inhibition of autophagy enhanced inflammatory injury via the ROS­mediated activation of the Nod­like receptor pyrin domain­containing protein 3 inflammasome. Autophagy may have a protective effect by mitigating inflammation in T2D, which may provide a novel approach for T2D treatment.

Mast cell stabilizer ketotifen reduces hyperalgesia in a rodent model of surgically induced endometriosis.

Purpose: This study aimed to investigate the effect of oral treatment with ketotifen, a mast cell (MC) stabilizer, in a rat model of surgically induced endometriosis. Methods: At 14 days after Sprague-Dawley rats had surgery, they were treated with ketotifen (1 or 10 mg/kg/day). Pain behaviors were evaluated 3 days prior to surgery and then at 7, 14, 21, and 28 days after surgery. At day 28, rats were sacrificed and all samples were then processed for biochemical studies. Results: We found that ketotifen-treated rats showed significantly shorter duration of hyperalgesia (p<0.05); smaller cyst diameter (p<0.05) and lower histopathologic score (p<0.001); significantly lower MC number and degranulation (p<0.001), blood vessel number (p<0.001), lower expression levels of nerve growth factor (p<0.001), cyclooxygenase-2 (p<0.001), intercellular cell adhesion molecule-1 (p<0.001), and vascular endothelial growth factor (p<0.05) in cysts, and nerve growth factor (p<0.001) and transient receptor potential cation channel, subfamily V, member 1 (p<0.001) in dorsal root ganglia; and lower histamine (p<0.05) and tumor necrosis factor-alpha (p<0.05) concentrations in serum compared with placebo-treated animal subjects. Conclusion: Oral treatment with ketotifen significantly suppressed the development of hyperalgesia, probably by modulating MC activity in cysts, thereby reducing peripheral sensitization due to noxious signals from endometriotic lesions. Our results suggest that ketotifen may inhibit the development of endometriotic lesions and hyperalgesia in rats.

LDC000067 suppresses RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced osteolysis in vivo.

Bone homeostasis requires a dynamic balance between osteogenesis and osteoclastogenesis, and osteolytic disorders are mainly attributed to aberrant osteoclastogenesis and bone resorption. Accumulating evidence has demonstrated that cyclin-dependent kinase 9 (CDK9) regulates some inflammatory diseases without affecting the cell cycle. Whether the specific inhibitor of CDK9, LDC000067 (abbreviated as LDC067), helps to prevent from osteolytic disorders has not been fully elucidated. Interestingly, this study demonstrated that LDC067 inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and bone resorption in vitro, and suppressed the expression of osteoclast-related marker genes such as cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP), dendrite cell-specific transmembrane protein (DC-STAMP), V-ATPase D2, calcitonin receptor (CTR) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). The bone protective effects of LDC067 can be partly explained by its suppression of nuclear factor-kappa B (NF-κB)-mediated NFATc1 activation via AKT signalling pathway. In keeping with the results obtained in vitro, inhibition of CDK9 with LDC067 was observed to delay subchondral osteolysis and substantially ameliorate LPS-induced osteolysis in murine calvaria. Collectively, these results highlight the positive effects of LDC067 in preventing osteolytic disorders and indicate that this CDK9 inhibitor may a promising therapeutic agent.

The posterolateral shearing tibial plateau fracture: treatment and results via a modified posterolateral approach.

The posterolateral shearing tibial plateau fracture is relatively uncommon and few studies have concentrated on it so far. The purpose of this study was to review the results of surgical treatment of this kind of fracture using a modified posterolateral approach. The clinical results of a case series of 11 patients, collected prospectively, were presented here. At final follow-up 10 out of 11 (91%) patients had satisfactory reduction of the articular surface and all had acceptable alignment. There was neither any loss in reduction or alignment at one year postoperation, with a mean HSS score of 93 (s.d. 3.67, range 84 to 97), nor superficial or deep infections, except that one case had a sanguinous effusion for more than one week postoperatively. It was concluded that the modified posterolateral approach could help to expand the surgical options for an optimal treatment of this kind of fracture, and plating of posterolateral shearing fractures would result in restoration and maintenance of alignment.

Liraglutide prevents high glucose level induced insulinoma cells apoptosis by targeting autophagy.

BACKGROUND: The pathophysiology of type 2 diabetes is progressive pancreatic beta cell failure with consequential reduced insulin secretion. Glucotoxicity results in the reduction of beta cell mass in type 2 diabetes by inducing apoptosis. Autophagy is essential for the maintenance of normal islet architecture and plays a crucial role in maintaining the intracellular insulin content by accelerating the insulin degradation rate in beta cells. Recently more attention has been paid to the effect of autophagy in type 2 diabetes. The regulatory pathway of autophagy in controlling pancreatic beta cells is still not clear. The aim of our study was to evaluate whether liraglutide can inhibit apoptosis and modulate autophagy in vitro in insulinoma cells (INS-1 cells). METHODS: INS-1 cells were incubated for 24 hours in the presence or absence of high levels of glucose, liraglutide (a long-acting human glucagon-like peptide-1 analogue), or 3-methyadenine (3-MA). Cell viability was measured using the Cell Counting Kit-8 (CCK8) viability assay. Autophagy of INS-1 cells was tested by monodansylcadaverine (MDC) staining, an autophagy fluorescent compound used for the labeling of autophagic vacuoles, and by Western blotting of microtubule-associated protein I light chain 3 (LC3), a biochemical markers of autophagic initiation. RESULTS: The viability of INS-1 cells was reduced after treatment with high levels of glucose. The viability of INS-1 cells was reduced and apoptosis was increased when autophagy was inhibited. The viability of INS-1 cells was significantly increased by adding liraglutide to supplement high glucose level medium compared with the cells treated with high glucose levels alone. CONCLUSIONS: Apoptosis and autophagy were increased in rat INS-1 cells when treated with high level of glucose, and the viability of INS-1 cells was significantly reduced by inhibiting autophagy. Liraglutide protected INS-1 cells from high glucose level-induced apoptosis that is accompanied by a significant increase of autophagy, suggesting that liraglutide plays a role in beta cell apoptosis by targeting autophagy. Thus, autophagy may be a new target for the prevention or treatment of diabetes.

Autophagy regulates inflammation following oxidative injury in diabetes.

T1D (type 1 diabetes) is an autoimmune disease characterized by lymphocytic infiltration, or inflammation in pancreatic islets called 'insulitis.' Comparatively speaking, T2D (type 2 diabetes) is traditionally characterized by insulin resistance and islet ß cell dysfunction; however, a number of studies have clearly demonstrated that chronic tissue inflammation is a key contributing factor to T2D. The NLR (Nod-like receptor) family of innate immune cell sensors such as the NLRP3 inflammasome are implicated in leading to CASP1 activation and subsequent IL1B (interleukin 1, ß) and IL18 secretion in T2D. Recent developments reveal a crucial role for the autophagy pathway under conditions of oxidative stress and inflammation. Increasingly, research on autophagy has begun to focus on its role in interacting with inflammatory processes, and thereby how it potentially affects the outcome of disease progression. In this review, we explore the pathophysiological pathways associated with oxidative stress and inflammation in T2D. We also explore how autophagy influences glucose homeostasis by modulating the inflammatory response. We will provide here a perspective on the current research between autophagy, inflammation and T2D.

[Failure of internal fixation on displaced femoral neck fractures in adults under fifty-five years old].

OBJECTIVE: To investigate the failure of internal fixation on displaced femoral neck fractures in adults under fifty-five years old retrospectively inorder to pay more attention to the treatment of these fractures. METHODS: From Junary 2007 to June 2010,18 failed cases of internal fixation on displaced femoral neck fractures in adults under fifty-five years old were treated,there were 13 males and 5 females with an average age of (48.0 +/- 6.0) years old ranging from 27 to 55. Among them, 17 patients were treated with cannulated screws and 1 patient was treated with intramedullary nail; 16 patients were diagnosed as osteonecrosis and 2 patients as osteonecrosis associated with nonunion. RESULTS: The average time from internal fixation to failure was 23 months (ranged, 8 to 32 months). The quality of fracture reduction in Garden index was poor. The Harris Hip Score was (56.0 +/- 12.5) (ranged,33 to 80). Eight cases of osteonecrosis and 2 cases of nonunion combinated osteonecrosis were received total hip arthroplasty. Hip resurfacing arthroplasty were performed for other 5 osteonecrosis. Because of no evident clinical symptoms,the other 3 cases received conservative treatment. The patients with total hip arthroplasty and hip resurfacing arthroplasty were followed-up for 34 months ranging from 12 to 53 months. After operation,the Harris score was (94.0 +/- 3.0) ranged 89 to 96. CONCLUSION: Osteonecrosis is a common complication after internal fixation on displaced femoral neck fracture in adults under fifty-five years old. More attention should be paid to the treatment of displaced femoral neck fracture in those patients.