Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

OBJECTIVE: To summarize the research progress of anterior cutaneous nerve injury and repair in knee arthroplasty. METHODS: The relevant literature at home and abroad in recent years was reviewed and summarized from the anatomy of anterior cutaneous nerve, nerve injury grade, clinical manifestations, prevention and treatment of anterior cutaneous nerve. RESULTS: The anterior cutaneous nerve injury is a common complication of knee arthroplasty. Because the anterior cutaneous nerve branches are many and thin, and mainly run between the first and second layers of fascia, this level is often ignored during surgical exposure. In addition, the knee arthroplasty does not routinely perform the exploration and repair of the cutaneous nerve. So the anterior cutaneous nerve injury is difficult to avoid, and can lead to postoperative skin numbness and knee pain. At present, studies have explored the feasibility of preventing its occurrence from the aspects of improved incision and intraoperative separation of protective nerve. There is no effective prevention and treatment measures for this complication. For patients with skin numbness after knee arthroplasty, the effectiveness of drug treatment is not clear. Local nerve block or nerve excision can be used to treat patients with painful symptoms after knee arthroplasty considering cutaneous pseudoneuroma. CONCLUSION Knee arthroplasty is widely used and anterior cutaneous nerve injury is common in clinic. In the future, more high-quality clinical studies are needed to further explore the prevention and treatment measures of this complication and evaluate the clinical benefits obtained.
Humans ; Arthroplasty, Replacement, Knee/adverse effects* ; Hypesthesia/etiology* ; Skin ; Pain/etiology* ; Knee Joint ; Pain, Postoperative

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m²) vs. (60±15) mL/(min·1.73 m²), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

At present, fatigue state monitoring of upper limb movement generally relies solely on surface electromyographic signal (sEMG) to identify and classify fatigue, resulting in unstable results and certain limitations. This paper introduces the sEMG signal recognition and motion capture technology into the fatigue state monitoring process and proposes a fatigue analysis method combining an improved EMG fatigue threshold algorithm and biomechanical analysis. In this study, the right upper limb load elbow flexion test was used to simultaneously collect the biceps brachii sEMG signal and upper limb motion capture data, and at the same time the Borg Fatigue Subjective and Self-awareness Scale were used to record the fatigue feelings of the subjects. Then, the fatigue analysis method combining the EMG fatigue threshold algorithm and the biomechanical analysis was combined with four single types: mean power frequency (MPF), spectral moments ratio (SMR), fuzzy approximate entropy (fApEn) and Lempel-Ziv complexity (LZC). The test results of the evaluation index fatigue evaluation method were compared. The test results show that the method in this paper has a recognition rate of 98.6% for the overall fatigue state and 97%, 100%, and 99% for the three states of ease, transition and fatigue, which are more advantageous than other methods. The research results of this paper prove that the method in this paper can effectively prevent secondary injury caused by overtraining during upper limb exercises, and is of great significance for fatigue monitoring.
Electromyography/methods* ; Fatigue ; Humans ; Muscle Fatigue ; Muscle, Skeletal ; Upper Extremity

Objective:To evaluate the medium-term clinical and hemodynamic outcomes of percutaneous pulmonary valve implantation (PPVI) using a domestic Venus-P self-expanding valve in the treatment of severe pulmonary regurgitation after Tetralogy of Fallot (TOF).Methods:Retrospective study.From December 2017 to December 2020, 13 TOF patients with (17.8±4.7) years old and (50.2±12.3) kg underwent PPVI using the Venus-P self-expanding valve in the Department of Children′s Heart Center, Zhengzhou University People′s Hospital were recruited.The mean valve size was (31.9±3.1) mm.All patients received the transannular patch surgery and developed severe pulmonary regurgitation.After PPVI, 13 patients were followed up for at least 12 months.The operation-related complications, improvement of valve and heart function and the durability and reintervention of the Venus-P self-expanding valve were analyzed.The right ventricular end-diastolic volume index (RVEDVi) before and after operation was compared by the paired t-test, and the New York Heart Association (NYHA) class was compared by the paired Wilcoxon signed rank sum test. Results:PPVI was successfully performed in all 13 patients without death.At 6 months post-PPVI, cardiac magnetic resonance imaging findings showed that RVEDVi was significantly reduced[(145.7±9.6) mL/m 2vs.(100.2±12.2) mL/m 2, P<0.05], and the NYHA class was significantly improved ( P<0.05). One patient presented moderate pulmonary valve regurgitation at 12 months postoperatively.No vegetation was found on echocardiography, and blood culture was negative in this case.Six patients did not have postoperative pulmonary valve regurgitation, and the remaining presented mild or less pulmonary regurgitation.One patient had sudden ventricular tachycardia on the 6 th day postoperatively, which was converted to sinus rhythm after synchronous electrocardiography.Only one case underwent appendectomy 7 months after operation due to acute appendicitis, and the remaining did not require valve-related reintervention after implantation.During the follow-up for (22.8±8.0) months, no patients had perivalve leakage, stent migration and rupture.Complications like embolization and coronary artery compression were not reported. Conclusions:PPVI using the Venus-P self-expanding valve is safe and effective in patients with severe pulmonary valve regurgitation after TOF surgery, showing an acceptable medium-term follow-up outcome.Studies with a large sample size and long follow-up period are still needed to validate our findings.

Objective:To summarize the clinical characteristics and treatment of cytomegalovirus(CMV)infection in pediatric kidney transplant patients.Methods:From May 2014 to July 2021, a total of 9 cases(8.65%)of 104 pediatric kidney transplant recipients were diagnosed with CMV infection in our centre.Retrospective data was collected for these 9 paediatric recipients.The clinical characteristics of the disease, treatment data and outcomes were summarized.Results:The median age of the 9 children was 10 years(0.25-15 years), 6 of whom were treated with polyclonal antibody for immunity induction.CMV IgG was negative in 4 children before renal transplantation.Only one patient received anti-CMV prophylaxis.The median time from transplant to the diagnosis of CMV infection was 22(7-15)days.Among the 9 children, 7 had fever, pneumonia and diarrhea, 2 had no typical symptoms, three patients were complicated with viral, bacterial or fungal infections.Acute rejection occurred in 3 patients at the same time as CMV infection or after CMV DNA turned negative.Nine patients were cured and discharged after ganciclovir or valganciclovir treatment.Median time of CMV DNA negative transformation was 32(17-90)days.Conclusions:Pediatric transplant recipients are at particularly elevated risk of CMV disease.Antiviral prophylaxis should be initiated early after transplantation.

Objective To investigate the underlying drug enhancement mechanisms of the Chuanwu (Aconiti Radix) and Huangqi (Astragali Radix) combination and toxicity reduction of Chuanwu combined with Gancao (Glycyrrhizae Radix et Rhizoma) in Wutou Decoction (乌头汤, WTD), and to elucidate the compatibility principle. Methods The active compounds and potential effective targets of the selected combinations were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicines Integrated Database (TCMID). The toxicity of Chuanwu (Aconiti Radix) was investigated by selecting all five toxic compounds from the literature and the TCMSP database, and obtaining their targets through SwissTargetPrediction. Targets related to rheumatoid arthritis (RA) were searched using DisGeNET, GenCards, and Online Mendelian Inheritance in Man (OMIM). Mutual targets between the drug pairs and RA were selected as potential RA therapy targets. The medicinally active compound-target network was constructed using Cytoscape 3.9.0. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Results We obtained 191 active compound targets for Gancao (Glycyrrhizae Radix et Rhizoma), 171 for Huangqi (Astragali Radix), and 103 for Chuanwu (Radix Aconiti) (hypoaconitine’s target was obtained through literature and SwissTargetPrediction). A total of 5872 genes were obtained for RA. A drug-active compound-target network involving 13 effect-enhancing and nine toxicity reduction targets was constructed. PGR was the main effect enhancement target, and KCNH2 was the main toxicity reduction target. The effect-enhancing targets were related to 23 GO terms (such as positive regulation of transcription from RNA polymerase II promoter, steroid hormone-mediated signaling pathway, plasma membrane, and protein binding) (P < 0.01), and 13 KEGG pathways related to synergism [such as estrogen signaling pathway, cholinergic synapse, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway]. The toxicity reduction targets were related to 28 GO terms (mainly involes G-protein coupled receptor signaling pathway, plasma membrane, and drug binding) (P < 0.01), and five KEGG pathways related to toxicity reduction (cholinergic synapse, calcium signaling pathway, regulation of actin cytoskeleton, neuroactive ligand-receptor interaction, and serotonergic synapse). Conclusion The combination of Chuanwu (Aconiti Radix) and Huangqi (Astragali Radix) plays an important effect-enhancing role in WTD and involves the estrogen and PI3K/Akt signaling pathways, with PGR as the core. The Chuanwu (Aconiti Radix) and Gancao (Glycyrrhizae Radix et Rhizoma) combination decreases toxicity in WTD and is associated with the cholinergic synapse and calcium signaling pathways, with KCNH2 as the core.

Objective:To investigate the clinical epidemiological data of children with prolonged mechanical ventilation (PMV) in pediatric intensive care unit(PICU), and analyze the primary disease of children with PMV as well as the disease characteristics and prognosis of children with PMV under different kinds of primary disease.Methods:The clinical data of hospitalized children with PMV in PICU at Children′s Hospital of Fudan University from January 2019 to December 2020 were retrospectively collected.Results:A total of 46 children with PMV were collected.There were 18 males (39.1%) and 28 females (60.9%). The median age was 37 (8, 86) months and the median body weight was 15 (7, 20) kg.The average pediatric critical illness score at admission was 84.2±7.7, PaO 2/FiO 2 was (245.5±99.8)mmHg.The primary diseases leading to PMV were as follows: there were 14 cases of severe pneumonia, eight cases of severe encephalitis, five cases of bronchopulmonary dysplasia, three cases of upper airway obstruction/craniofacial deformity, three cases of myasthenia, three cases of brain stem tumor, three cases of mitochondrial encephalomyopathy, two cases of spinal muscular atrophy, two cases of Prader-Willi syndrome, one case of dermatomyositis, one case of severe brain injury, and one case of central hypoventilation.The causes of unable to withdraw ventilator were respiratory dysfunction in 24 cases, brain dysfunction in 16 cases, and diaphragm dysfunction in six cases.Compared with neuromuscular diseases, children with PMV caused by respiratory diseases had lower month age, higher preterm birth rate, lower PaO 2/FiO 2 ratio, higher parameters for ventilator treatment, and the differences were statistically significant ( P<0.05). Children with PMV caused by neuromuscular diseases had lower Glasgow coma score and higher coma rate, and the differences were statistically significant ( P<0.05). A total of nine (19.6%) cases underwent tracheotomy.A total of 23 (50.0%) cases were successfully extubated from ventilator, six (13.0%) cases were dependent on invasive ventilator, and six (13.0%) cases were breathing with tracheotomy tube.The median mechanical ventilation time was 33 (28, 40) days, the median PICU hospital stay was 42 (34, 56) days, and the median hospital stay was 51 (41, 65) days.A total of 27 (58.7%) cases were improved and discharged, four (8.7%) cases were transferred to rehabilitation hospital, four (8.7%) cases were transferred to local hospital, and 11 (23.9%) cases died in hospital or at home after giving up. Conclusion:The main causes of PMV in PICU children are respiratory dysfunction, brain dysfunction and diaphragm dysfunction.50.0% of the children with PMV could be discharged from the ventilator, and 23.9% died or died after giving up.