In recent years,tumor immunotherapy has attracted more attention because of its remarkable curative effect in patients with advanced cancer,but often accompanied by immune related adverse events.Understanding the immune related adverse reaction rate,possible mechanism and adverse reaction evaluation criteria and treatment principle of the immune checkpoint inhibitors such as Ipilimumab,Nivolumab and Pembrolizumab,has important significance for the treatment of malignant tumor.

Breast cancer stem cells (CSCs) are the main causes leading to the failure of treatment of breast cancer and play important roles in the progression of breast cancer and drug resistance, which are closely related to the therapeutic resistance of radiotherapy and chemotherapy, and endocrine therapy.The metastatic potential and therapeutic resistance of CSCs are associated with epithelial mesenchymal transition and Hedgehog, Wnt, interleukin-6/signal transduction and tanscriptional activation factor 3, transforming growth factor-β and other signaling pathways.While some of the targeted drugs targeting these signaling pathways are undergoing clinical transformation, which is expected to provide new approach for the clinical treatment of breast cancer.

Objective:To detect the mRNA expression levels of inflammatory-related factors NLRP3, caspase-1, IL-1β, and IL-18in the murine macrophages infected by periodontitis patient's own tissue nucleic acid, and to discuss the effects of periodontitis patient's own tissue nucleic acid on the inflammation-related factors in the macrophages.Methods:The inflammatory periodontal tissue samples were collected during periodontal flap surgery of the chronic periodontitis patients, and the healthy periodontal tissue samples were collected from the patients without any periodontal diseases undergoing crown lengthening surgery.Then the total RNA from gingival tissue was extracted and reversely transcribed into cDNA.The cultured mouse macrophages RAW264.7were divided into control group and experiment group, then the healthy periodontal tissue cDNA and inflammatory periodontal tissue cDNA (the cDNA at a concentration of 1mg·L-1) were added into the RAW264.7cells, respectively.Real-time PCR was used to detect the mRNA expression levels of NLRP3, Caspase-1, IL-1β, and IL-18in the macrophages in various groups at 4, 6and 8hafter incubation.Results:The microscope observation showed that the mouse macrophages RAW264.7grew well with round and polygon shapes, clear cytoplasm, and full cell body.Compared with control group, the expression levels of NLRP3, Caspase-1, IL-1β, and IL-18mRNA in the RAW264.7cells in experiment group at 4, 6, and 8hwere increased significantly (P＜0.05or P＜0.01) , and the expression levels of NLRP3, Caspase-1, IL-1β, and IL-18 mRNA in RAW264.7 cells at 6 hin experiment group were the highest.Conclusion:The periodontitis patient's own tissue nucleic acids can promote the mRNA expressions of inflammation-related factors in the RAW264.7cells, suggesting that the periodontitis patient's own tissue nucleic acid has an immunomodulatory effect on the activation of RAW264.7cells.

China still has more than 30,000 patients of advanced schistosomiasis while new cases being reported consistently. D-dimer is a fibrin degradation product. As ascites being the dominating symptom in advanced schistosomiasis, the present study aimed to explore a prediction model of ascites with D-dimer and other clinical easy-achievable indicators. A case-control study nested in a prospective cohort was conducted in schistosomiasis-endemic area of southern China. A total of 291 patients of advanced schistosomiasis were first investigated in 2013 and further followed in 2014. Information on clinical history, physical examination, and abdominal ultrasonography, including the symptom of ascites was repeatedly collected. Result showed 44 patients having ascites. Most of the patients' ascites were confined in the kidney area with median area of 20 mm². The level of plasma D-dimer and pertinent liver function indicators were measured at the initial investigation in 2013. Compared with those without ascites, cases with ascites had significantly higher levels of D-dimer (0.71±2.44 μg/L vs 0.48±2.12 μg/L, P=0.005), as well ALB (44.5 vs 46.2, g/L) and Type IV collagen (50.04 vs 44.50 μg/L). Receiver operating characteristic curve analyses indicated a moderate predictive value of D-dimer by its own area under curve (AUC) of 0.64 (95% CI: 0.54–0.73) and the cutoff value as 0.81 μg/L. Dichotomized by the cutoff level, D-dimer along with other categorical variables generated a prediction model with AUC of 0.76 (95% CI: 0.68–0.89). Risks of patients with specific characteristics in the prediction model were summarized. Our study suggests that the plasma D-dimer level is a reliable predictor for incident ascites in advanced schistosomiasis japonica patients.
Area Under Curve ; Ascites* ; Case-Control Studies ; China ; Cohort Studies ; Collagen Type IV ; Fibrin ; Humans ; Kidney ; Liver ; Physical Examination ; Plasma* ; Prospective Studies* ; ROC Curve ; Schistosoma japonicum ; Schistosomiasis japonica* ; Schistosomiasis* ; Ultrasonography

Objective:Hereditary neuropathy with liability to pressure palsy(HNPP)is a rare autosomal dominant peripheral neuropathy,usually caused by heterozygous deletion mutations in the peripheral myelin protein 22(PMP22)gene.This study aims to investigate the clinical and molecular genetic characteristics of HNPP. Methods:HNPP patients in the Department of Neurology at Third Xiangya Hospital of Central South University from 2009 to 2023 were included in this study.The general clinical data,nervous electrophysiological and molecular genetic examination results were collected and analyzed.Molecular genetic examination was to screen for deletion of PMP22 gene using multiplex ligation-dependent probe amplification(MLPA)after extracting genomic DNA from peripheral blood;and if no PMP22 deletion mutation was detected,next-generation sequencing was used to screen for PMP22 point mutations.The related literatures of HNPP were reviewed,and the clinical and molecular genetic characteristics of HNPP patients were analyzed. Results:A total of 34 HNPP patients from 24 unrelated Chinese Han families were included in this study,including 25 males and 9 females.The average age at illness onset was 22.0 years.Sixty-two point five percent of the families had a positive family history.Among them,30 patients had symptoms of peripheral nerve paralysis.Patients often presented with paroxysmal single limb weakness with(or)numbness(25/30),and some patients had paroxysmal unilateral recurrent laryngeal nerve(vagus nerve)paralysis(2/30).Physical examination revealed muscle weakness(23/29),hypoesthesia(9/29),weakened or absent ankle reflexes(20/29),distal limb muscle atrophy(8/29)and high arched feet(5/29).Most patients(26/30)could fully recover to normal after an acute attack.Thirty-one patients in our group underwent nervous electrophysiological examination,and showed multiple demyelinating peripheral neuropathies with both motor and sensory nerves involved.Most patients showed significantly prolonged distal motor latency(DML),mild to moderate nerve conduction velocity slowing,decreased amplitude of compound muscle action potential(CMAP)and sensory nerve action potential(SNAP),and sometimes with conduction block.Nerve motor conduction velocity was(48.5±5.5)m/s,and the CMAP amplitude was(8.4±5.1)mV.Nerve sensory conduction velocity was(37.4±10.5)m/s,and the SNAP amplitude was(14.4±15.2)μV.There were 24 families,23 of whom had the classical PMP22 deletion,the last one had a heterozygous pathogenic variant in the PMP22 gene sequence(c.434delT).By reviewing clinical data and genetic testing results of reported 1 734 HNPP families,we found that heterozygous deletion mutation of PMP22 was the most common pathogenic mutation of HNPP(93.4%).Other patients were caused by PMP22 small mutations(4.0%),PMP22 heterozygous gross deletions(0.6%),and PMP22 complex rearrangements(0.1%).Thirty-eight sorts of HNPP-related PMP22 small mutations was reported,including missense mutations(10/38),nonsense mutations(4/38),base deletion mutations(13/38),base insertion mutations(3/38),and shear site mutations(8/38).HNPP patients most often presented with episodic painless single nerve palsy.Common peroneal nerve,ulnar nerve,and brachial plexus nerve were the most common involved nerves,accounting for about 75%.Only eighteen patients with cranial nerve involved was reported. Conclusion:Heterozygous deletion mutation of PMP22 is the most common pathogenic mutation of HNPP.Patients is characterized by episodic and painless peripheral nerve paralysis,mainly involving common peroneal nerve,ulnar nerve,and other peripheral nerves.Nervous electrophysiological examination has high sensitivity and specificity for the diagnosis of HNPP,which is manifested by extensive demyelinating changes.For patients with suspected HNPP,nervous electrophysiological examination and PMP22-MLPA detection are preferred.Sanger sequencing or next generation sequencing can be considered to detect other mutations of PMP22.

Objective To evaluate the application value of absorbable hemostat textile as submucosal injection of endoscopic submucosal dissection(ESD). Methods Twelve New Zealand rabbits were injected with absorbable hemostat textile solution,glycerol fructose and normal saline. The uplift effect was measured after injection. Simulated ESD was performed in the rabbit stomach and bleeding amount was measured. The injection site was pathologically examined at 30 minutes after the soluble hemostat textile and normal saline were injected. Fifteen pigs were injected with absorbable hemostat textile at two locations of 20-30 cm from the anus,and injected normal saline at another two locations of 20-30 cm from the anus.One site was performed simulated ESD and the other was not. Fifteen simulated ESD were performed in the soluble hemostatic group and the normal saline group, respectively. Operation time was recorded and difference in wound healing was compared between the two groups. Results In the uplift experiment, the absorbable hemostat textile group had higher uplift height(4.3±1.4 mm,4.1±1.9 mm,3.8±0.7 mm, 3.3±0.9 mm, respectively)at 0 min,10 min,20 min,30 min than that of the glycerol fructose group(4.3±2.2 mm,4.1± 2.0 mm,3.6±1.4 mm, 3.2±0.8 mm, respectively, P<0.05), and the glycerol fructose group was higher than that of the normal saline group(3.8±1.6 mm,2.6±1.4 mm,1.9±1.9 mm,1.1±0.7 mm, P<0.05). There was no significant difference in uplift height between the absorbable hemostat textile group and the glycerol fructose group(P>0.05). In the bleeding experiment, the bleeding amount of absorbable hemostat textile group was significantly less than that of the glycerol fructose group(0.36±0.07 mL VS 0.42±0.06 mL, P<0.05);the bleeding amount of glycerol fructose group was significantly lower than that of the normal saline group(0.42±0.06 mL VS 0.55±0.07 mL,P<0.05). There was no obvious tissue necrosis and other adverse complications in the absorbable hemostat textile group and the normal saline group. In simulated ESD experiment,complete resection rate of the absorbable hemostat textile group was higher than that of the normal saline group[86.7%(13/15)VS 46.7%(7/15), P<0.05], and mean operation time of the absorbable hemostat textile group was less than that of the normal saline group(3.2± 0.3 min VS 3.8± 0.5 min, P<0.05). No hemorrhage, perforations or other related adverse events occurred in non-ESD lesions. Conclusion Absorbable hemostat textile is safe and effective as submucosal injection of ESD.

Themedical's () infantgenre in western Hunan Province is one of the most famous infantgenres in China. Based on physiological and pathological characteristics of infants, generation-inhibition theory of five-elements andmedical's promotion-inhibition theory of five-meridians, theprotocol of "" was flexibly adjusted; according to different constitution types, including lung-deficiency type, spleen-deficiency type, kidney-deficiency type,-deficiency type,-deficiency type,-deficiency type, phlegm-wet type, phlegm-heat type, different protocols were adopted to prevent or reduce the asthma recurrence and reach the aim of regulating constitution and disease prevention.

Immune checkpoint inhibitors (ICIs) present significant efficacy in the treatment of malignant tumors, and they have been approved as the first-line of treatment for various cancers. Pembrolizumab monotherapy or combined with chemotherapy has been recommended by domestic and foreign guidelines for the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma. Although ICIs represent a milestone in the treatment of head and neck squamous cell carcinoma, potential problems still need to be addressed, such as the selection of the efficacy predictors for ICIs, the evaluation of the tumor response to ICIs, and the treatment of immune hyperprogression and immune-related adverse events. Therefore, to form a relatively unified understanding of ICIs treatment for head and neck squamous cell carcinoma, we integrated the clinical experience of multi-disciplinary experts of head and neck cancers on the basis of current clinical hot issues and finally developed this consensus.
Humans ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immune Checkpoint Inhibitors ; Consensus ; Neoplasm Recurrence, Local/pathology* ; Head and Neck Neoplasms/drug therapy*