Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

Objective:Based on gene expression omnibus(GEO),differential expressed genes,gene set enrichment analysis(GSEA)and immune cell infiltration analysis were performed on microarray data of chronic spontaneous urticaria(CSU)expression profile,to gain more insight into the pathogenesis of CSU.Methods:The GSE72541 raw data were obtained from the GEO.Differential expressed genes were screened using R software.String database were used to construct the the protein-protein interaction(PPI)net-work.Gene ontology(GO)and Kyoto encyclopedia of gene and genomes(KEGG)enrichment analysis were performed using GSEA software.The ssGSEA method was used to analyze the infiltration of immune cells in the expression profile.Results:Genes closely related to platelet activation and its function were up-regulated in CSU serum,while genes related to Th1 cell chemotaxis were down-regulated in CSU serum.Biological processes and signal pathways related to coagulation cascade reaction,regulation of vascular per-meability,immune and inflammatory reactions,and mood-modulating were up-regulated in CSU group.Immunized cell infiltration analysis showed that activated B cells,immature B cells,follicular helper T cells,and Th2 cells were down-regulated in the CSU serum.Conclusion:Platelet activation,coagulation cascade reaction and the imbalance of Th1/Th2 immunity play important roles in the pathogenesis of CSU.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

The anterior cruciate ligament (ACL), anterolateral complex (ALC) and lateral meniscus (LM) maintain the anterolateral rotatory stability of the knee and control the internal rotation of the tibia. Anterolateral rotatory instability (ALRI) of the knee is not uncommon in clinic, and its main injury mechanism is non-contact injury. A pivot shift test or a tibial internal rotation test can indicate ALRI while X-ray, CT, MRI and ultrasound can assist in its diagnosis and differential diagnosis. For acute ALRI, good technique of ACL reconstruction is the basis to avoid postoperative residual ALRI, and anterolateral ligament reconstruction and extra-articular tenodesis are optional as appropriate. For chronic cases, however, both anterolateral ligament reconstruction and extra-articular tenodesis are effective. This article reviews the progress in research on the diagnosis and treatment of ALRI of the knee, hoping to provide references for its clinical diagnosis and treatment.

Objective To observe the clinical efficacy of Lingnan Traditional Vesiculating Moxibustion No.4 Recipe(mainly composed of Brassicae Junceae Semen,Euodiae Fructus,and Curcumae Radix)in the treatment of mild depressive disorder(DD),and to provide a novel approach to the treatment of mild DD population.Methods Sixty-one patients with mild DD were randomly divided into 31 cases in the trial group and 30 cases in the control group.The trial group was given medicinal vesiculation treatment with Lingnan Traditional Vesiculating Moxibustion No.4 Recipe,and the control group was given medicinal vesiculation treatment with the placebo of Lingnan Traditional Vesiculating Moxibustion No.4 Recipe.The treatment was performed twice a week and with an interval of 3-4 days between the treatment,and the course of treatment covered 6 weeks.The changes of Hamilton Depression Scale-17(HAMD-17)scores and Patient Health Questionnaire-9(PHQ-9)scores in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After 6 weeks of treatment,the total efficacy rate of the trial group was 77.42%(24/31),and that of the control group was 26.67%(8/30).The intergroup comparison(tested by rank sum test)showed that the efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.01).(2)After treatment,the HAMD-17 scores and PHQ-9 scores of patients in the two groups were lower than those before treatment(P＜0.01),and the decrease of HAMD-17 and PHQ-9 scores in the trial group was significantly superior to that of the control group,the difference being statistically significant(P＜0.01).(3)During the trial,there were 5 cases of adverse events related to the vesiculating moxibustion treatment,and all 5 cases of adverse events occurred in the trial group,manifested as minor blisters at the acupoint application region.The 5 cases kept on participating in the trial after relevant treatment.Conclusion Lingnan Traditional Vesiculating Moxibustion No.4 Recipe can effectively relieve the clinical symptoms of patients with mild DD,and has high safety.

Objective To explore the effectiveness of high-definition diffusion weighted imaging(DWI)sequence combined with T1 WI-fat suppression(FS)dynamic contrast enhancement(DCE)sequence for preoperative T-stage of rectal cancer by using 3.0T MRI standardized scanning.Methods A retrospective analysis was conducted on MRI images of 57 patients with rectal cancer confirmed by pathology.Before surgery,the patients underwent 3.0T MRI standardized rectal cancer scan methods,including routine sequence,high-definition DWI sequence,and T1 WI-FS DCE sequence,etc.Then two experienced physicians evaluated the T-stage of preoperative rectal cancer through high-definition DWI(transverse and sagittal sections)and T1 WI-FS DCE sequences in the double-blind method.Using the postoperative pathological results of rectal cancer as the"gold standard",two sequences were combined to evaluate the accuracy,sensitivity,and specificity of rectal cancer T-stage.Results Among the 57 cases,there were 9 cases of upper rectal cancer,39 cases of middle rectal cancer,and 9 cases of lower rectal cancer.The accuracy rates of preoperative T-stage diagnosis for rectal cancer by two evaluator were both 85.7％(6/7)in T1 stage,88.2％(15/17)and 94.1％(16/17)in T2 stage,96.9％(31/32)and 93.8％(30/32)in T3 stage,and both 100.0％(1/1)in T4 stage.For evaluator 1,the sensitivity and specificity of the rectal cancer T-stage diagnosis were 96.1％and 83.3％,and for evaluator 2 were 94.1％and 83.3％,respectively.For rectal cancer MRI diagnosis,the accuracy rates and sensitivity were higher when combining the high-definition DWI sequence and T1 WI-FS DCE sequence,compared with a single high-definition DWI sequence or T1 WI-FS DCE sequence,and the difference was statistically significant.The average preoperative apparent diffusion coefficient(ADC)value of rectal cancer was compared between the corresponding postoperative pathological T1 to T4 stage groups,and the difference was statistically significant.Conclusion The combination of high-definition DWI sequence and T1 WI-FS DCE sequence improves the accuracy of rectal cancer T-stage,providing assistance for personalized clinical treatment.

Emaciation is a common physical condition in clinical practice,often accompanied by symptoms related to"excessive fire in thin people".Insufficient yin-qi is the main physiological and pathological basis of emaciation,and excessive dryness-heat is the secondary manifestation.The disease involves five viscera,with the spleen as the core.The principle of treatment is to nourish yin-qi as the main method,and to dissipate stagnant heat as the auxiliary method.Specifically,it includes two aspects:treating the root cause and treating the symptoms.Treating the root cause should nourish yin-qi to improve the"emaciation"constitution,and treating the symptoms should dissipate stagnant heat to eliminate the"excessive fire"state.The importance of the two should be determined ac-cording to the severity and urgency of the excessive fire.Clinically,the addition and subtraction of medicinal ingredients are made ac-cording to factors such as the urgency of the root cause and symptoms,the state of emaciation and the ability to eat,the degree of defi-ciency or excess of fire-heat,the pathogenesis of the disease,and the season.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Aim To express and purify rhα-Gal A with a 6 X His tag via using a serum-free expression system in high-density suspension culture of Chinese hamster ovary cells ( CHO-S) , and to verify the scavenging effect of rhα-Gal A on globular trisaccharide ceramide (Gb3 or GL3) . Methods The construction of recombinant protein expression vector, pcDNA4-GLA, was achieved by fusing the human α-galactosidase cDNA, gla, with 6 X His tag and artificial DNA synthesis. The expression plasmid was transfected into the suspended CHO-S to express rhα-Gal A and then purified. Following this procedure, we determined rhα-Gal A's expression, the enzymatic activity, and the glycosylation of the recombinant enzyme. Co-incubation with cultured cells was performed to examine whether rhα-Gal A could be taken up into the cells and effectively remove Gb3 substrates. Results rhα-Gal A was successfully expressed and purified after transiently transfecting pcDNA4-GLA into the suspended CHO-S, and the yield was up to (100 ±20. 6) mg • L

Objective:To retrospectively analyze clinical characteristics and treatment of pemphigus/bullous pemphigoid (BP) complicated by herpes simplex virus (HSV) infection.Methods:Inpatients with pemphigus/BP complicated by HSV infection were collected from Wuhan No.1 Hospital from 2016 to 2021, and their clinical characteristics, treatment and follow-up results were retrospectively analyzed.Results:Among the 8 patients with pemphigus/BP complicated by HSV infection, there were 2 males and 6 females, and their age was 50.6 ± 8.3 years. Five of them were diagnosed with pemphigus vulgaris (PV), 1 with pemphigus foliaceus (PF), and 2 with BP. Seven were infected with HSV-1, and 1 with HSV-2. All the 8 patients were given systemic glucocorticoids and immunosuppressive agents for the treatment of pemphigus or BP, and were admitted to the hospital due to resistance to the treatment. Seven patients presented with exacerbation or recurrence of primary lesions, and 1 presented with enlarged lesions all over the body. HSV infection-induced lesions were located on the trunk in 4 cases, on the oral mucosa in 4, on the scalp in 3, and on the face in 2; lesions mainly manifested as irregular erosions with blood crusts, and some centrally umbilicated pustules; 7 patients had obvious pain at the lesional sites. During HSV infection, anti-desmoglein 1 antibody levels decreased in all the 6 patients with pemphigus, and anti-desmoglein 3 antibody levels decreased in 4 of the 5 patients with pemphigus vulgaris; anti-BP180 antibody levels decreased in 1 patient with BP, but increased in the other one with BP. After antiviral therapy at adequate doses for adequate durations (7- to 14-day treatment with valacyclovir alone or in combination with ganciclovir), HSV infection was controlled, the autoimmune bullous skin disorder intensity scores decreased compared with those before the antiviral therapy, and pain was significantly relieved in all the patients. No dose adjustment of glucocorticoids or other immunosuppressive agents was made during antiviral therapy in all patients.Conclusion:HSV infection should be considered when patients with pemphigus/BP suffer from recurrence or exacerbation and poorly respond to conventional treatment; for patients with pemphigus/BP complicated by HSV infection, systemic antiviral therapy at adequate doses can be used to control the disease condition without modifying the conventional immunosuppressive regimen.