Tumor necrosis factor-stimulated gene-6 ameliorates early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome-mediated astrocyte pyroptosis

Subarachnoid hemorrhage is associated with high morbidity and mortality and lacks effective treatment.Pyroptosis is a crucial mechanism underlying early brain injury after subarachnoid hemorrhage.Previous studies have confirmed that tumor necrosis factor-stimulated gene-6(TSG-6)can exert a neuroprotective effect by suppressing oxidative stress and apoptosis.However,no study to date has explored whether TSG-6 can alleviate pyroptosis in early brain injury after subarachnoid hemorrhage.In this study,a C57BL/6J mouse model of subarachnoid hemorrhage was established using the endovascular perforation method.Our results indicated that TSG-6 expression was predominantly detected in astrocytes,along with NLRC4 and gasdermin-D(GSDMD).The expression of NLRC4,GSDMD and its N-terminal domain(GSDMD-N),and cleaved caspase-1 was significantly enhanced after subarachnoid hemorrhage and accompanied by brain edema and neurological impairment.To explore how TSG-6 affects pyroptosis during early brain injury after subarachnoid hemorrhage,recombinant human TSG-6 or a siRNA targeting TSG-6 was injected into the cerebral ventricles.Exogenous TSG-6 administration downregulated the expression of NLRC4 and pyroptosis-associated proteins and alleviated brain edema and neurological deficits.Moreover,TSG-6 knockdown further increased the expression of NLRC4,which was accompanied by more severe astrocyte pyroptosis.In summary,our study revealed that TSG-6 provides neuroprotection against early brain injury after subarachnoid hemorrhage by suppressing NLRC4 inflammasome activation-induced astrocyte pyroptosis.

Early prediction and prevention of infected pancreatic necrosis

Approximately 20%-30%of patients with acute necrotizing pancreatitis develop infected pancreatic necrosis(IPN),a highly morbid and potentially lethal complication.Early identification of patients at high risk of IPN may facilitate appropriate preventive measures to improve clinical outcomes.In the past two decades,several markers and predictive tools have been proposed and evaluated for this purpose.Conventional biomarkers like C-reactive protein,procalcitonin,lymphocyte count,interleukin-6,and interleukin-8,and newly developed biomarkers like angiopoietin-2 all showed significant association with IPN.On the other hand,scoring systems like the Acute Physiology and Chronic Health Evaluation II and Pancreatitis Activity Scoring System have also been tested,and the results showed that they may provide better accuracy.For early prevention of IPN,several new therapies were tested,including early enteral nutrition,anti-biotics,probiotics,immune enhancement,etc.,but the results varied.Taken together,several evidence-supported predictive markers and scoring systems are readily available for predicting IPN.However,effective treatments to reduce the incidence of IPN are still lacking apart from early enteral nutrition.In this editorial,we summarize evidence concerning early prediction and prevention of IPN,providing insights into future practice and study design.A more homo-geneous patient population with reliable risk-stratification tools may help find effective treatments to reduce the risk of IPN,thereby achieving individualized treatment.

The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice

Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

Treatment of primary nasal tuberculosis with anti-tumor necrosis factor immunotherapy:A case report

BACKGROUND Primary nasal tuberculosis(TB)is a rare form of extrapulmonary TB,particularly in patients receiving anti-tumor necrosis factor(TNF)immunotherapy.As a result,its diagnosis remains challenging.CASE SUMMARY A 58-year-old male patient presented to the ear,nose,and throat department with right-sided nasal obstruction and bloody discharge for 1 month.He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation.Biopsy findings revealed chronic granulomatous inammation and a few acid-fast bacilli,suggestive of primary nasal TB.He was referred to our TB management department for treatment with oral anti-TB agents.After 9 months,the nasal lesions had disappeared.No recurrence was noted during follow-up.CONCLUSION The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate,particularly when pathological findings suggest granulomatous inflammation.

Bilateral Avascular Necrosis of the Femoral Head in Renal Transplant Recipient: A Case Report

Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These complications lead to significant morbidity and mortality, in addition to chronic pain and functional impairment. We report the clinical case of bilateral avascular necrosis (AVN) of the femoral head in a kidney transplant recipient. Clinical Case: 53-year-old male with a history of chronic hypertension. He underwent chronic hemodialysis for 12 months and was treated with Entecavir for chronic hepatitis B. The patient received a kidney transplant from a non-related living donor. Induction therapy included Thymoglobulin along with tapered corticosteroids, reaching a dose of 5 mg/day after 3 months, Mycophenolate mofetil (2 g/day), and Tacrolimus adjusted based on residual levels. There was good recovery of renal graft function. After six months, the patient reported bilateral hip pain and functional impairment of both lower limbs. Pelvic X-rays showed signs suggestive of bilateral AVN of the femoral heads. The diagnosis was confirmed by MRI. The patient underwent right hip drilling and total left hip replacement (THR). A right THR was performed a year later. Conclusion: AVN constitutes a frequent cause of morbidity and mortality after RT. The pathophysiology of osteonecrosis remains complex and multifactorial. We emphasize the importance of conducting a thorough assessment of bone health in patients both before and after RT.

Sequential bowel necrosis and large gastric ulcer in a patient with a ruptured femoral artery:A case report

BACKGROUND Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency department.Bowel necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood supply.In this case,we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric ulcer.CASE SUMMARY A 28-year-old male patient sustained a knife stab wound to the right thigh,causing rupture of his femoral artery and leading to massive bleeding.He underwent cardiopulmonary resuscitation and received a large blood transfusion.Abdominal surgeries confirmed bowel necrosis,and jejunostomy was performed.The necrotic intestine was removed,the remaining intestine was anastomosed,and the right thigh was amputated.After three surgeries,the patient's overall condition gradually improved,and the patient was discharged from the hospital.However,one day after discharge,the patient was admitted again due to dizziness and melena,and a gastroduodenoscopy revealed a giant banded ulcer.After 2 weeks of treatment,the ulcer had decreased in size without bleeding.Six months after the last surgery,enterostomy and reintroduction surgery were completed.The patient was fitted with a right lower limb prosthesis one year after surgery.After 3 years of follow-up,the patient did not complain of discomfort.CONCLUSION Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

Endoscopic treatment of bleeding gastric ulcer causing gastric wall necrosis:A case report

BACKGROUND Gastric wall necrosis is a rare complication of endoscopic treatment for bleeding gastric ulcer,which may exacerbate the patient’s condition once it occurs and may even require surgical intervention for treatment.CASE SUMMARY A 59-year-old man was admitted to our department with melena.Endoscopy revealed a giant ulcer in the gastric antrum with a visible vessel in its center,which was treated with sclerosants and tissue glue injection and resulted in necrosis of the gastric wall.CONCLUSION Injection of sclerosants and tissue glue may lead to gastric wall necrosis,which is a serious complication.Therefore,before administering this treatment to patients,we should consider other more effective methods of hemostasis to avoid gastric wall necrosis.

Early screening to identify and diagnose primary nasal tuberculosis in patients with tumor necrosis factor inhibitors

In this editorial,we comment on the article by Liu et al.Based on our analysis of a case report,we consider that early screening and recognition of primary nasal tuberculosis are crucial for patients undergoing treatment with tumor necrosis factor inhibitor(TNFi).While TNFi therapy increases the risk of reactivating latent tuberculosis,primary nasal tuberculosis remains rare due to the protective mechanisms of the nasal mucosa.Risk factors for primary nasal tuberculosis include minimally invasive nasal surgery,diabetes,and human immunodefi ciency virus.Patients with early symptoms such as nasal congestion,rhinorrhea,altered olfaction,epistaxis,or ulceration,and unresponsive to conventional antibiotics and antihistamines should undergo early rhinoscopy,possibly followed by repeated tissue biopsies and acid-fast bacilli culture when necessary.When diagnosis is challenging,it is essential to consider local tuberculosis epidemiology and the efficacy of diagnostic antituberculosis treatment.The preferred method for tuberculosis screening is the Interferon Gamma Release Assay,with a general recommendation for screening at 3 and 6 months after initial treatment and then every six months.However,the optimal frequency is not yet consensus-driven and may be increased in economically viable settings.

Changes in postoperative depression and anxiety and their relationship with recovery from femoral head necrosis:A longitudinal study

BACKGROUND Femoral head necrosis(FHN)can significantly affect patients'psychological well-being and functional outcomes.However,the long-term relationship between postoperative depression,anxiety,and functional recovery in patients with FHN remains unclear.AIM To investigate the dynamic changes in postoperative depression and anxiety and their relationship with functional recovery in patients with FHN for 3 years.METHODS Ninety-three patients with FHN who underwent surgical treatment in March 2020 to 2023 were enrolled in this longitudinal study.Depression and anxiety status were assessed using the hospital anxiety and depression scale(HADS)at baseline,6 months,1,2,and 3 years postoperatively.Functional recovery was evaluated using the Harris hip score(HHS).The dynamic changes in HADS and HHS were analyzed using repeated measures ANOVA;the relationship between depre-ssion/anxiety status and functional recovery was examined using Pearson’s correlation analysis.RESULTS The mean HADS-depression(HADS-D)and HADS-anxiety(HADS-A)scores significantly improved over time(P<0.001).The prevalence of depression and anxiety decreased from 36.6%and 41.9%at baseline to 10.8%and 12.9%,respectively,at 3 years postoperatively.The mean HHS increased sig-nificantly from 52.3±10.5 at baseline to 88.1±7.2 at 3 years postoperatively(P<0.001).Significant negative correl-ations were found between HADS-D/HADS-A scores and HHS at all time points(P<0.05).CONCLUSION The severity of depression and anxiety negatively correlated with functional recovery,highlighting the importance of psychological interventions in the management of patients with FHN.

Reliability of neutrophil gelatinase-associated lipocalin in detecting acute tubular necrosis in decompensated cirrhosis:Systematic review and meta-analysis

BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be used to assess the type of AKI and the severity of the disease.We performed a systematic review with metaanalysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin(NGAL)marker in identifying acute tubular necrosis(ATN)in patients with cirrhosis.AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis.METHODS We systematically searched MEDLINE and PubMed using keywords including“urine biomarkers”,“NGAL”,“kidney dysfunction”,and“cirrhosis”to identify relevant studies.Data was screened and extracted.Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker.We synthesized the data using diagnostic odds ratio(DOR),comparative and descriptive analyses,and Cochran Mantel-Haenszel(CMH)statistics to evaluate heterogeneity.RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies.The DOR of 14 of those studies[pooled DOR:22.150,(95%CI:17.58-27.89),P<0.0001]demonstrated a significant association between urine NGAL levels and its identification of ATN.Following stratification by cirrhosis status,heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI(CMH statistic=702.19,P<0.0001).CONCLUSION In patients with cirrhosis,the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.

Diagnostic and management challenges in primary cutaneous anaplastic large cell lymphoma with necrosis,inflammation,and surgical intervention:A case report

BACKGROUND Primary cutaneous anaplastic large cell lymphoma(PC-ALCL)poses significant diagnostic difficulties due to its similarity in the appearance of skin lesions with chronic inflammatory disorders and other dermatological conditions.This study aims to investigate these challenges by conducting a comprehensive analysis of a case presenting with PC-ALCL,emphasizing the necessity of accurate differentiation for appropriate management.CASE SUMMARY An 89-year-old female patient with diabetes and hypertension presented with arm and abdominal ulcerated mass lesions.Diagnostic procedures included skin biopsies,histopathological assessments,and immunohistochemistry,complemented by advanced imaging techniques to confirm the diagnosis.The patient’s lesions were determined as PC-ALCL,characterized by necrosis,chronic inflammation,and a distinct immunophenotypic profile,including CD30,CD3,CD4,and EBER,CD56,MUM-1,Ki 67-positive in>80%of tumor cells,CD10,but negative for anaplastic lymphoma kinase,CD5,CD20,PAX-5,Bcl-2,Bcl-6,CD8,and CD15.Recurrence was not reported at the 6-month follow-up.CONCLUSION Accurate PC-ALCL differentiation from similar conditions is crucial for effective management and requires a multidisciplinary approach.

Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine A

BACKGROUND Dry eye is a common eye disease.Artificial tears supplements are widely used for the treatment of dry eyes.However,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic effect.AIM To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A.METHODS A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same period.Levels of inflammatory markers,including IL-1β,IL-6,and TNF-α,were analyzed.The observation group was further divided into a study group and a control group,each consisting of 62 patients.The control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine A.Inflammatory markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two groups.RESULTS The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy group.Following treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control group.Moreover,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group.Additionally,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study group.Furthermore,post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group(P<0.05).It is noteworthy that significant AEs were reported in both groups throughout the treatment period.CONCLUSION Cyclosporine A combined with artificial tears is effective in treating dry eye,yielding enhanced outcomes by improving SIT and TBUT levels,reducing CFS scores,and ameliorating vision-related quality of life.

Predicting full-thickness necrosis in adult acute corrosive ingestion injuries in a sub-Saharan African setting

BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international investigative algorithms,relying heavily on computed tomography(CT),having limited availability in this setting.AIM To investigate the corrosive injury spectrum in a low-resource setting and the applicability of parameters for predicting full-thickness(FT)necrosis and mortality.METHODS A retrospective analysis of a prospective corrosive injury registry(March 1,2017–October 31,2023)was performed to include all adult patients with acute corrosive ingestion managed at a single,academic referral centre in Cape Town,South Africa.Patient demographics,corrosive ingestion details,initial investigations,management,and short-term outcomes were described using descriptive statistics while multivariate analysis with receiver operator characteristic area under the curve graphs(ROC AUC)were used to identify factors predictive of FT necrosis and 30-day mortality.RESULTS One-hundred patients were included,with a mean age of 32 years(SD:11.2 years)and a male predominance(65.0%).The majority(73.0%)were intentional suicide attempts.Endoscopy on admission was the most frequent initial investigation performed(95 patients),while only 17 were assessed with CT.Seventeen patients had full thickness necrosis at surgery,of which eleven underwent emergency resection and six were palliated.Thirty-day morbidity and mortality were 27.0%and 14.0%,respectively.Patients with full thickness necrosis and those with an established perforation had a 30-day mortality of 58.8%and 91.0%,respectively.Full thickness necrosis was associated with a cumulative 2-year survival of only 17.6%.Multivariate analyses with ROC AUC showed admission endoscopy findings,CT findings,and blood gas findings(pH,base excess,lactate),to all have significant predictive value for full thickness necrosis,with endoscopy proving to have the best predictive value(AUC 0.850).CT and endoscopy findings were the only factors predictive of early mortality,with CT performing better than endoscopy(AUC 0.798 vs 0.759).CONCLUSION Intentional corrosive injuries result in devastating morbidity and mortality.Locally,early endoscopy remains the mainstay of severity assessment,but referral for CT imaging should be considered especially when blood gas findings are abnormal.

Early versus delayed necrosectomy in pancreatic necrosis:A population-based cohort study on readmission,healthcare utilization,and in-hospital mortality

BACKGROUND Acute necrotizing pancreatitis is a severe and life-threatening condition.It poses a considerable challenge for clinicians due to its complex nature and the high risk of complications.Several minimally invasive and open necrosectomy procedures have been developed.Despite advancements in treatment modalities,the optimal timing to perform necrosectomy lacks consensus.AIM To evaluate the impact of necrosectomy timing on patients with pancreatic necrosis in the United States.METHODS A national retrospective cohort study was conducted using the 2016-2019 Nationwide Readmissions Database.Patients with non-elective admissions for pancreatic necrosis were identified.The participants were divided into two groups based on the necrosectomy timing:The early group received intervention within 48 hours,whereas the delayed group underwent the procedure after 48 hours.The various intervention techniques included endoscopic,percutaneous,or surgical necrosectomy.The major outcomes of interest were 30-day readmission rates,healthcare utilization,and inpatient mortality.RESULTS A total of 1309 patients with pancreatic necrosis were included.After propensity score matching,349 cases treated with early necrosectomy were matched to 375 controls who received delayed intervention.The early cohort had a 30-day readmission rate of 8.6% compared to 4.8%in the delayed cohort(P=0.040).Early necrosectomy had lower rates of mechanical ventilation(2.9%vs 10.9%,P<0.001),septic shock(8%vs 19.5%,P<0.001),and in-hospital mortality(1.1%vs 4.3%,P=0.01).Patients in the early intervention group incurred lower healthcare costs,with median total charges of $52202 compared to$147418 in the delayed group.Participants in the early cohort also had a relatively shorter median length of stay(6 vs 16 days,P<0.001).The timing of necrosectomy did not significantly influence the risk of 30-day readmission,with a hazard ratio of 0.56(95%confidence interval:0.31-1.02,P=0.06).CONCLUSION Our findings show that early necrosectomy is associated with better clinical outcomes and lower healthcare costs.Delayed intervention does not significantly alter the risk of 30-day readmission.

Efficacy of Laparoscopic Cholecystectomy in Treating Patients with Gallstones and Its Effect on Interleukin-6 and Tumor Necrosis Factor-α Levels

Objective:To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-a).Methods:A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method,with 41 cases in each group.The patients were treated with laparoscopic cholecystectomy,with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group.The treatment effect and inflammatory factor levels of both groups were observed and compared.Results:When comparing the clinical outcomes of both patient groups,the key parameters evaluated included time to mobilization,duration of surgery,extubation time,and intraoperative bleeding.The observation group exhibited a significant advantage in these parameters compared to the control group(P<0.05).Regarding the levels of inflammatory factors between the two groups before and after treatment,there was no significant difference in values before treatment.However,following treatment,patients in the observation group showed significantly lower levels of IL-6,TNF-α,and C-reactive protein(CRP)compared to the control group(P<0.05).Conclusion:Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder,which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6,TNF-α,and CRP.Therefore,it is recommended for the widespread adoption of this treatment approach in clinical practice.

Bilateral pericapsular end nerve blocks for steroid-induced avascular necrosis following COVID-19 infection requiring bilateral total hip replacement

BACKGROUND Osteonecrosis or avascular necrosis(AVN)of the hip was one of the dreaded complications of coronavirus disease 2019(COVID-19),which emerged in patients who received steroid therapy.Corticosteroids have been a mainstay in the treatment protocol of COVID-19 patients.Popular corticosteroid drugs used in patients suffering from COVID-19 were intravenous(IV)or oral dexamethasone,methylprednisolone or hydrocortisone.The use of such high doses of corticost-eroids has shown very positive results and has been lifesaving in many cases.Still,long-term consequences were drug-induced diabetes,osteoporosis,Cushing syndrome,muscle wasting,peripheral fat mobilization,AVN,hirsutism,sleep disturbances and poor wound healing.A significant number of young patients were admitted for bilateral total hip replacements(THR)secondary to AVN following steroid use for COVID-19 treatment.AIM To assess the efficacy of bilateral pericapsular end nerve group(PENG)blocks in patients posted for bilateral THR post-steroid therapy after COVID-19 infection and assess the time taken to first ambulate after surgery.METHODS This prospective observational study was conducted between January 2023 and August 2023 at Care Hospitals,Hyderabad,India.Twenty young patients 30-35 years of age who underwent bilateral THR were studied after due consent over 8 months.All the patients received spinal anaesthesia for surgery and bilateral PENG blocks for postoperative analgesia.RESULTS The duration of surgery was 2.5 h on average.Seventeen out of twenty patients(85%)had a Visual Analog Score(VAS)of less than 2 and did not require any supplementation.One patient was removed from the study,as he required re-exploration.The remaining two patients had a VAS of more than 8 and received IV morphine post-operatively as a rescue analgesic drug.Fifteen out of seventeen patients(88.2%)could be mobilized 12 h after the procedure.CONCLUSION Osteonecrosis or AVN of the hip was one of the dreaded complications of COVID-19,which surfaced in patients who received steroid therapy requiring surgical intervention.Bilateral PENG block is an effective technique to provide post-operative analgesia resulting in early mobilization and enhanced recovery after surgery.

Recombination Mutant Human Tumor Necrosis Factor Combined with Chemotherapy in the Treatment of Advanced Cancer

Objective: Past studies showed that tumor necrosis factor (TNF) assisted anti-tumor treatment and intensified the sensitivity of chemotherapy. However its clinical application has been curbed because of its low purity, high dosage, and strong toxicity. The objective of present study is to evaluate the therapeutic effects and adverse reactions of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy in patients with advanced malignant tumor. Methods: 105 patients with advanced malignant tumor were randomly divided into trial group, 69 patients, and control group, 36 patients. rmhTNF was injected intramuscularly to the trial group at a dose of 4×106 U/m2, from the 1st to 7th days, the 11th to 17th days combined with chemotherapy course. The chemotherapy plan was as follows: CAP for patients with the NSCLC; FAM for patients with gastric cancer; FC for patients with colorectal cancer. One treatment cycle lasted for 21 days and two cycles were scheduled. The control group was given only the same chemotherapy as the trial group. Results: In the trial group there was 1 CR case and 12 PR cases, and the response rate was 13/69 (18.84%); in the control group 1 PR case, the response rate 1/36 (2.78%). The response rate in the trial group was significantly higher than that in the control group (P=0.022). The response rate for NSCLC in the trial group was 8/17 (47.06%), and 1/6 (16.67%) in the control group. The response rates for gastric cancer and colorectal cancer in the trial groups also were higher than those in the control groups. After the treatment the KPS was 89.00±9.92 in the trial group, and 84.17±8.84 in the control group, with a significant difference between the two groups (P=0.028). The adverse reactions of rmhTNF injection included: pain in the injection area, chill, hardening and swelling and redness in the injection area, fever, ostealgia and myosalgia, and cold-like symptoms. All these adverse reactions were mild and bearable. Conclusion: The administration of rmhTNF in combination with general chemotherapy is an effective and secure means in treating advanced malignant tumor.

An Experimental Study of Pathogenesis of Steroid-induced Avascular Necrosis of Femoral Head

Objective: To explore the pathogenesis of avascular necrosis of femoral head(ANFH) and search an effective method for clinical practice. Methods: Twenty-four Japanese rabbitswere divided into 2 groups of models and controls. ANFH models were produced byintramuscular-injection of large dosage of steroid to rabbits for 8 weeks. From the 4th, 8th and12th week after production of models, 2 rabbits of each group were sacrificed to observe thestructure of femoral head through light microscope and scanning electron microscope. The contents ofNitric Oxide (NO), tissue-type plasminogen activator (t-PA) and -plasminogen activator inhibitor(PAI) in plasma of the 4 rabbits in each group were estimated at the same time. Results: Comparedwith control group, the rabbits of model group exhibited many differences: such as osteoporosis offemoral head, the presence of more bone lacuna and fat cell through light microscope observing; thebroken and sunk bone trabecula, the loosen and broken collagen fibers on the surface of bone matrixthrough scanning electron microscope observing. Compared with control group, the Concentration ofNO and t-PA in plasma of the model rabbits decreased obviously, but the Concentration of the PAIincreased obviously. Conclusion: The steroid-induced ANFH might be related to the lower level of NOand the descent of fibrinolytic activity.

术后腹腔粘连形成机制及间充质干细胞外泌体的治疗前景

背景:术后腹腔粘连的形成是一个复杂的过程,预防术后粘连是临床上亟待解决的问题。目的:旨在从细胞及分子水平分析粘连的发生机制,为间充质干细胞外泌体预防和治疗粘连提供理论依据。方法:以“腹腔粘连,盆腔粘连,术后粘连,上皮间充质转化,间充质干细胞,干细胞外泌体,间充质干细胞外泌体”为中文检索词,以“Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cell,stem cell exosomes,mesenchymal stem cell exosomes”为英文检索词,检索PubMed、中国知网和中国生物医学文献数据库,筛选各数据库建库至2023年8月发表的术后腹腔粘连及间充质干细胞外泌体干预研究的相关文章,并进行系统的整理分析,最终纳入54篇文献进行综述。结果与结论:(1)任何腹膜炎症、机械损伤、组织缺血和异物植入等病理因素均可引起腹膜表面的损伤,引起术后腹腔粘连;腹腔粘连的形成过程包括腹膜间皮细胞修复、炎性反应、纤溶系统及凝血途径等过程的相互作用,涉及多种细胞因子及信号通路,包括Wnt/β-catenin通路能诱导纤维化和血管生成,并与转化生长因子β/Smads信号通路相互协同,能刺激成纤维细胞增殖,引起腹膜纤维化;同时,核转录因子kB信号通路上调细胞炎症因子的表达,促进成纤维细胞增生,组织纤维化的过程中发挥关键作用。(2)干细胞的旁分泌功能是目前以再生医学为基础的分子干预腹腔粘连的重要方向,可以参与作用于腹腔粘连中的多种复杂细胞因子及信号通路。(3)相对于传统治疗腹腔粘连的方法,间充质干细胞外泌体具有生物活性、使用安全、无需特殊培养和扩增、更低的免疫原性及较长的稳定性等优势,能通过多种途径引导一种正常的修复和愈合。(4)间充质干细胞外泌体在以往研究中均被证明可以参与调节粘连形成的上述各过程,在临床研究中显示出潜在的应用前景,但需要进一步临床研究以探索适当的间充质干细胞外泌体治疗方案,来解决临床转化的问题。

创伤性股骨头坏死病人术前临床病史与全髋关节置换术后深静脉血栓的相关性分析

目的研究创伤性股骨头坏死(FHN)病人术前临床病史与全髋关节置换术(THA)后深静脉血栓的相关性。方法回顾性分析2014年8月至2022年5月共172例因创伤性FHN来南京中医药大学常熟附属医院行单侧THA术的病人临床资料。所有病人均在THA术后行常规低分子肝素(LWMH)抗凝,并于术后第3天行双下肢静脉B超检查。按检查结果将病人分成DVT组(男22例,女4例,平均年龄64.35岁)和非DVT组(男102例,女44例,平均年龄62.35岁)。分别比较两组病人术前基本临床病史如既往VTE病史、糖尿病、高血压、冠心病(CHD)等与DVT的具体相关性并通过多变量分析DVT发生的危险因素。结果DVT组中CHD发病率为73.08%(19/26),显著高于非DVT组的31.51%(46/146)。创伤性FHN病人合并CHD[OR=6.63,95%CI:(1.49,29.59),P=0.013]或长期吸烟史[OR=4.58,95%CI:(1.26,16.62),P=0.021]是THA术后DVT的发生危险因素。结论冠心病和吸烟史是创伤性FHN病人行单侧THA术后DVT发生的危险因素,对于此类病人需重视术前疾病控制,同时应规范手术操作以减少术后DVT的发生。