OBJECTIVE To explore the effects of CD20 coding gene （MS4A1） polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020， with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software， including rs1051461， rs17155034， rs4939364， and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors（demographic， clinical， and genotypic variables） in patients and the steady-state trough concentration of rituximab during the first course of treatment， followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival （PFS） and overall survival （OS）. Using MS4A1 genotype and tumor stage as independent variables， Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL，which was significantly lower than 21.95 μg/mL in AA+AC carriers （P＜0.05）. The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers， CT+TT carriers had significantly prolonged PFS and OS （P＜0.05）. The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype （HR＝4.406， 95%CI：1.743-11.137， P＜0.05） and tumor Ⅲ&Ⅳ （HR＝3.233， 95%CI： 1.413-7.399， P＜0.05） were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab， and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.

Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

Objectives: . Reactive oxygen species in the stria vascularis (SV) of the cochlea may be involved in the pathogenesis of sensorineural hearing loss. However, the effects of oxidative stress on SV endothelial cells (SV-ECs) remain largely unknown, and no feasible in vitro cell culture model exists for the functional study of SV-ECs. Methods: . We isolated primary SV-ECs from the SV of neonatal mice. The apoptosis-reducing effects of fibronectin in SV-ECs cultured with serum-free medium were determined using β-galactosidase staining and flow cytometry. SV-ECs incubated in serum-free medium were treated with various H2O2 concentrations to evaluate the effects of H2O2 on their viability. The secretome of SV-ECs treated with or without H2O2 (100 μM or 500 μM) was analyzed using high-resolution mass spectrometry. The function of the SV-EC secretome was evaluated by a macrophage assay. Results: . We successfully isolated and characterized the SV-ECs. Treatment with H2O2 at concentrations up to 500 μM for 2 hours and further incubation with serum-free medium in plates precoated with fibronectin showed no significant effect on apoptosis. Compared to the control SV-ECs, the amount of differential proteins in the secretome of SV-ECs stimulated with 500 μM H2O2 was much higher than in those treated with 100 μM H2O2. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses suggested that the proteins differentially expressed in SV-ECs treated with 500 μM H2O2 were involved in the regulation of multiple signaling pathways and cellular processes. The secretome of H2O2-stimulated SV-ECs exhibited significant pro-inflammatory effects on macrophages. Conclusion . We successfully established an in vitro serum-free culture method, identified the differential proteins released by oxidative stress-induced ECs and their functions, and revealed the pro-inflammatory effects of the secretome of H2O2-stimulated SV-ECs. Therefore, SV-ECs might elicit immunoregulatory effects on bystander cells in the microenvironment of oxidative stress-induced cochlea, especially cochlear macrophages.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

The 2019 Academic Annual Meeting of the Chinese Burn Association, sponsored by the Chinese Medical Association and the Chinese Burn Association, was successfully held in Zhuhai, Guangdong province, from November 6th to 9th, 2019. The theme of this conference was " One China, One Standard--Data Standardization and Construction of National Burn Data Platform" . A total of 2 305 submissions and 1 749 e-posters were received, and 1 097 registered representatives, nearly 2 000 representatives from 9 countries and regions attended the meeting. Focusing on the theme of this conference, a variety of novel forms were adopted such as teaching contest of young surgeons, multi-disciplinary discussion, workshop, and surgery live broadcast on hot issues in key areas of burns. Besides, with the focus on humanistic care and innovation, a multi-disciplinary discussion was warmly conducted. The 2020 academic annual conference is scheduled to be held in Nanchang, China.

Objective: To assess the interobserver variations in delineating the planning target volume (PTV) and organs at risk (OAR) using different contouring methods during intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), aiming to provide references for the quality control of multi-center clinical trials. Methods: The PTV and OAR of CT image of 1 NPC patient manually delineated by 10 physicians from 8 different radiation centers were defined as the " manual contour group" , and the OAR auto-contoured using the ABAS software and modified by the physicians were defined as the " auto+ manual contour group" . The maximum/minimum ratio (MMR) of the PTV and OAR volumes, and the coefficient of variation (CV) for different delineated contours were comparatively evaluated. Results: Large variation was observed in the PTV and OAR volumes in the manual contour group. The MMR and CV of the PTV were 1.72-3.41 and 0.16-0.39, with the most significant variation in the PTV_nd (MMR=3.41 and CV=0.39 for the PTV_nd-L). The MMR and CV of the manually contoured OAR were 1.30-7.89 and 0.07-0.67. The MMR of the temporal lobe, spinal cord, temporomandibular joint, optic nerve and pituitary gland exceeded 2.0. Compared with the manual contour group, the average contouring time in the auto+ manual group was shortened by 68% and the interobserver variation of the OAR volume was reduced with an MMR of 1.04-2.44 and CV of 0.01-0.37. Conclusions Large variation may occur in the PTV and OAR contours during IMRT plans for NPC delineated by different clinicians from multiple medical centers. Auto-contouring+ manually modification can reduce the interobserver variation of OAR delineation, whereas the variation in the delineation of small organs remains above 1.5 times. The consistency of the PTV and OAR delineation and the possible impact upon clinical outcomes should be reviewed and evaluated in multi-center clinical trials.

V-erb-a erythroblastic leukemia viral oncogene homolog 4 (ERBB4) has been reported to be somatically mutated in 19% of melanoma cases. To investigate the prevalence of ERBB4 mutations in melanoma patients from southern China, we analyzed 117 formalin-fixed, paraffin-embedded melanoma samples archived in the Sun Yat-sen University Cancer Center. A matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform was used to screen for mutations. No ERBB4 hotspot mutations were detected. Our results indicate that ERBB4 mutations may play a limited role in melanomas in China; therefore, targeting the ERBB4 mutation in melanoma patients from southern China may not be a promising strategy.
Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; DNA, Neoplasm ; genetics ; Extremities ; Female ; Humans ; Male ; Melanoma ; genetics ; metabolism ; Middle Aged ; Mucous Membrane ; Mutation ; Paraffin Embedding ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Receptor, ErbB-4 ; Skin Neoplasms ; genetics ; metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Fluid therapy has been the focus of attention and dispute. In this paper, there are three aspects including postoperative bowel function, surgical prognosis, and acute diffuse peritonitis. Colloidal supplement and appropriate crystal/colloid ratio should be noted in low perfusion conditions. The different types of fluid in recent studies did not show a significant difference in the long term. The new evidence will be noted in fluid therapy among 2012 SSC Severe Sepsis and Septic Shock Guideline update (unpublished).
Digestive System Surgical Procedures ; Fluid Therapy ; Humans ; Perioperative Care ; Peritonitis ; therapy ; Prognosis ; Shock, Septic ; therapy

BACKGROUNDLupus hepatitis is yet to be characterized based on its clinical features and is often difficult to differentially diagnose from other liver diseases. We aimed to elucidate clinical, histopathological and immunopathological features of lupus hepatitis and to evaluate primarily the effectiveness of liver immunopathological manifestations on differential diagnosis of lupus hepatitis from other liver diseases.

METHODSA retrospective study was performed to analyze clinical features of lupus hepatitis in 47 patients out of 504 inpatients with systemic lupus erythematosus (SLE) in First Affiliated Hospital of Sun Yat-sen University, China from May 2006 to July 2009, and to evaluate the association between lupus hepatitis and SLE activity. Additionally, liver histopathological changes by hematoxylin and eosin (HE) staining and immunopathological changes by direct immunofluorescence test in 10 lupus hepatitis cases were analyzed and compared to those in 16 patients with other liver diseases in a prospective study.

RESULTSOf 504 SLE patients, 47 patients (9.3%) were diagnosed to have lupus hepatitis. The prevalence of lupus hepatitis in patients with active SLE was higher than that in those with inactive SLE (11.8% vs. 3.2%, P < 0.05). The incidence of hematological abnormalities in patients with lupus hepatitis was higher than that in those without lupus hepatitis (40.4% vs. 21.7%, P < 0.05), such as leucocytes count (2.92×10(9)/L vs. 5.48×10(9)/L), platelets count (151×10(9)/L vs. 190×10(9)/L), serum C3 and C4 (0.34 g/L vs. 0.53 g/L; 0.06 g/L vs. 0.09 g/L) (P < 0.05); 45 of 47 (95.7%) lupus hepatitis patients showed 1 upper limit of normal (ULN) < serum ALT level < 5 ULN. The liver histopathological features in patients with lupus hepatitis were miscellaneous and non-specific, similar to those in other liver diseases, but liver immunopathological features showed positive intense deposits of complement 1q in 7/10 patients with lupus hepatitis and negative complement 1q deposits in all patients with other liver diseases (Fisher's exact test, P = 0.011).

CONCLUSIONSLupus hepatitis was not infrequent in active SLE patients which would be one of the indices indicating SLE activity. Positive intense deposit of complement 1q in liver may be a characteristic immunopathological feature of lupus hepatitis, which provides a new way to differentially diagnose lupus hepatitis from other liver diseases.

Adolescent ; Adult ; Aged ; Child ; Cohort Studies ; Complement C1q ; analysis ; Female ; Hepatitis, Autoimmune ; etiology ; immunology ; pathology ; Humans ; Liver ; pathology ; Lupus Erythematosus, Systemic ; complications ; Male ; Middle Aged ; Retrospective Studies

The precondition of accurate gastric cancer surgery is precise assessment of lymph node metastasis. To date, no imaging modality achieves both high sensitivity and high specificity in detecting lymph node metastasis in gastric cancer. Intraoperative sentinel node tracing and biopsy are the most popular method to identify the localization of tumor cell, but is limited to early gastric cancer. Nano-composite materials, designed for tumor imaging and tracing, show us a newly emerging domain for tumor detection in gastric cancer. The function of these nano-composite materials to detect lymph node metastasis in gastric cancer relies on the effective backflow of lymph system. However, the lymph vessels can be obstructed by tumor cells in advanced gastric cancer, which may restrain the application of these nanoparticles. Therefore, more methods to detect lymph node metastasis in gastric cancer should be explored. This review summarizes the characteristic of the targeted nanosphere. Based on the reported studies, a novel idea is conceived that targeted multifunctional nanosphere may be a potential method to achieve precise assessment of lymph node metastasis in gastric cancer.
Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; pathology ; Stomach Neoplasms ; pathology