The application of immune checkpoint inhibitors has changed the treatment paradigm for advanced non-small cell lung cancer(NSCLC).However,interruption of immune checkpoint inhibitor therapy due to intolerable adverse effects or due to disease progression has become a problematic issue in the treatment of advanced NSCLC.Whether immune checkpoint inhibitors rechallenge therapy is possible after interruption of immune checkpoint inhibitor therapy has been proposed and remains controversial.This article summarizes the types of immune checkpoint inhibitor rechallenge and therapeutic strategies for advanced NSCLC,and finds that patients with NSCLC who have interrupted their immunotherapy due to immune-related adverse events and clinical decision-making can still achieve a better favorable clinical outcomes.It is hypothesized that immune checkpoint inhibitor rechallenge for NSCLC after drug resistance is an alternative salvage therapy.

The application of immune checkpoint inhibitors has changed the treatment paradigm for advanced non-small cell lung cancer(NSCLC).However,interruption of immune checkpoint inhibitor therapy due to intolerable adverse effects or due to disease progression has become a problematic issue in the treatment of advanced NSCLC.Whether immune checkpoint inhibitors rechallenge therapy is possible after interruption of immune checkpoint inhibitor therapy has been proposed and remains controversial.This article summarizes the types of immune checkpoint inhibitor rechallenge and therapeutic strategies for advanced NSCLC,and finds that patients with NSCLC who have interrupted their immunotherapy due to immune-related adverse events and clinical decision-making can still achieve a better favorable clinical outcomes.It is hypothesized that immune checkpoint inhibitor rechallenge for NSCLC after drug resistance is an alternative salvage therapy.

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

Objective:To analyze and evaluate the safety and efficacy of a Chinese domestically manufactured Heart Con-type implantable third-generation magnetic and hydrodynamic levitation left ventricular assist device(LVAD) for the treatment of end-stage heart failure(ESHF), by reporting the results of eleven-center clinical trial on 50 cases.Methods:This study was a multicenter clinical trial, designed by means of prospective, multicenter and single-group target value. 50 subjects with ESHF were competitively enrolled and treated with HeartCon as the LVAD in eleven centers. The primary efficacy measure was survival, defined as either the subjects experiencing the transition to heart transplantation(HT) or myocardial recovery assisted by the device within 90 days, or as successfully assisted by the LVAD for full 90 days after implantation. The target survival rate was 60%, other observations included implantation success rate, mortality, pump failure needing replacement or emergency heart transplantation.Results:All enrolled 50 patients received LVAD implantation successfully, 46 survived with the pump for 90 days, 1 patient transitioned to heart transplantation, and 3 patients experienced pump thrombosis, within which 2 patients underwent pump replacement and continued to live with the pump for 90 days, and the other one received emergency heart transplantation. There were no dropout subjects. The survival rate at full 90 days after HeartCon implantation was 100%. The survival rates with pump in the full set analysis and the protocol set analysis were 96.00% and 95.92% respectively, which were higher than the target value of 60%. The differences were both statistically significant( P<0.05). Conclusion:The results of the multicenter clinical trial with the largest sample size in China using domestically manufactured third-generation LVAD has demonstrated that, HeartCon is a safe and effective LVAD to treat ESHF patients.

Objective:To investigate the risk factors of bone cement leakage after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A multi-center, large-sample, case-control study was carried out to analyze the clinical data of 2 273 OVCF patients (2 689 vertebrae) undergone PVP at four hospitals between May 2018 and October 2021, including 994 males and 1 279 females, with the age of 52-91 years [(69.1±3.1)years]. Of all, 581 patients (604 vertebrae) were allocated to leakage group and 1 692 patients (2 085 vertebrae) to no leakage group according to the occurrence of bone cement leakage. The gender, age, fracture sites, vertebral compression degree, endplate integrity of fractured vertebrae, surgical segments, surgical approaches and bone cement injection volume were recorded. Univariate analysis was used to investigate the correlation between those indicators with bone cement leakage. Multivariate Logistic regression analysis was used to identify the independent risk factors for bone cement leakage.Results:Univariate analysis showed that gender, age, fracture sites, vertebral compression degree, bone cement injection volume were related to bone cement leakage after PVP ( P<0.05 or 0.01), but no correlation was found in the endplate integrity of fractured vertebrae, surgical segments and surgical approaches (all P>0.05). Multivariate Logistic regression analysis showed that fracture sites ( OR=1.68, 95% CI 1.11-2.55, P<0.05), vertebral compression degree more than 40% ( OR=1.98, 95% CI 1.29-3.02, P<0.01), bone cement injection volume greater than or equal to 5.5 ml ( OR=1.55, 95% CI 1.07-2.26, P<0.05) were significantly associated with bone cement leakage after PVP. Conclusion:Thoracic vertebral fracture, vertebral compression degree more than 40% and bone cement injection volume greater than or equal to 5.5 ml are independent risk factors for bone cement leakage after PVP in OVCF.

Objective:To explore the treatments and outcomes of heart and kidney transplantation(HKTx)and summarize its management experiences.Methods:From October 2016 to October 2020, clinical data, treatment strategies and prognosis of 11 patients received HKTx were analyzed retrospectively.In 11HKTx cases, the ratio of male-to-female was 10∶1, the age(50.6±12.9)years and the preoperative body mass index(26.72±3.29)kg/m 2.The preoperative cardiac function was class Ⅳ and the preoperative left ventricular ejection fraction(29.40±4.48)%.All patients were in uremic state pre-operation and underwent regular dialysis.The mean duration of dialysis was 2.5(0.5-7.0)years, preoperative creatinine 753.5(434-1144)μmol/L and preoperative predictive glomerular filtration rate 5.59(3.93-17.23)ml/(min preop 2). Non-staged transplant was performed and donor heart and kidney were from the same donor.The median time of cold cardiac ischemia 2.75(2.5, 4.0)hours, the median time of cold renal ischemia 9(8.5, 15.0)hours and the median time from the end of heart transplantation to the beginning of kidney transplantation 2(1.0, 3.5)hours.The immunosuppressive regimen was a combination of tacrolimus, mycophenolate mofetil and methylprednisolone. Results:Normal cardiac function and renal function normalized in 9 cases.At Month 6 post-operation, the postoperative left ventricular ejection fraction was(57.55±2.51)%, creatinine 107.7(85-132)μmol/L and urine volume in 24h 1988(1800-2200)ml.The long-term survival time was 6-62 months.No such complications as infection or rejection occurred in 9 patients.The cardiac function was class Ⅰ at Month 6 post-operation.One patient died from pulmonary mucor infection at Month 4 post-operation.Another death was due to gastrointestinal fungal infection at Month 1 after HKTx.Conclusions:HKTx is an effective treatment for end-stage heart disease with renal failure.

Programmed cell death-1/programmed cell death-ligand 1(PD-1/PD-L1) inhibitors have been approved for a variety of tumors, whereas the efficacy as monotherapy is low. How to sensitize the efficacy of PD-1/PD-L1 inhibitors through combined radiotherapy is the current research focus. Multiple studies have demonstrated that the combination of radiotherapy and anti-PD-1/PD-L1 therapy has yielded survival benefits. Nevertheless, ionizing radiation is a double-edged sword for anti-PD-1/PD-L1 therapy. For patients with metastatic cancers, radiotherapy should be fully exerted as a sensitizer to systemic anti-PD-1/PD-L1 therapy and the immunosuppressive effects should be avoided as much as possible. It is closely correlated with the selection of radiation dose, fraction size, treatment timing and irradiated numbers and sites. Therefore, this article reviews how to optimize radiotherapy combined with anti-PD-1/PD-L1 treatment scheduled for advanced stage metastatic cancers.

Objective To summarize the outcomes and clinical experience of combined heart and kidney transplantation.Methods The clinical data of one case of combined heart and kidney transplantation were retrospectively analyzed.The kidney transplant was completed immediately after the heart transplant.The immunosuppressive therapy strategies included tacrolimus,corticosteroids and mycophenolate mofetil.Results For heart transplantation,heart cold ischemia time was 200 min,aorta blocking time was 136 min,and extracorporeal circulation time was 201 min.The kidney was transplanted to the right iliac fossa after heart transplantation.The endotracheal tube was removed 15 h after surgery.The patient was transferred to the general ward on the 8th day after surgery.The patient was discharged from the hospital at 27th day after surgery,the renal function was normal and no activity was restricted.Conclusion Reasonable perioperative management and selection of surgical methods are the keys to the success of combined heart and kidney transplantation.

The incidence of dextrocardia is lower. The dextrocardia is often associated with congenital anatomical abnormalities. The patient with normal cardiac structure of dextrocardia and severe coronary heart disease that needs coronary artery bypasss is rarer. This article summarizes the perioperative management and surgical experience of dextrocardia with bypass surgery via a clinical case.

Objective To summarize the treatment experiences in patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods The clinical data of 9 patients with acute renal injury after orthotopic heart transplantation in our hospital from January 2009 to July 2016 were retrospectively analyzed. Three patients were required the high-dose diuretics (furosemide, >80 mg/d) and six patients were received continuous renal replacement therapy (CRRT). The levels of serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) were compared before and after heart transplantation and after the treatment of AKI. The quality of life was observed in patients in perioperative period. Results After the treatment of diuretics or CRRT, patients showed renal function recovery with significant decreased Cr levels and increased eGFR compared with the postoperation. The patients with diuretic therapy revealed a better eGFR recovery than those with CRRT. Conclusion CSA-AKI should be based on the severity of disease, and comprehensive treatment should be taken to reduce renal damage.