三级淋巴结构在肿瘤免疫治疗中的研究进展

三级淋巴结构(tertiary lymphoid structures,TLS)是指在病理生理环境下,淋巴细胞在非淋巴器官内聚集形成的有组织的异位淋巴结构。成熟的TLS包括被T细胞包围的B细胞区域和生发中心,普遍存在于多个瘤种中,是肿瘤细胞与免疫细胞相互作用的重要场所,与患者预后密切相关。因此,诱导形成TLS,使T细胞和B细胞发育分化为能够识别杀伤肿瘤细胞的效应细胞和记忆细胞,可以介导抗肿瘤免疫反应。本综述主要介绍了TLS的组成成分和形成过程,总结归纳现有的检测手段,强调了TLS不同成熟度、位置和内部组成等特征对肿瘤免疫疗效的影响和预测价值,并探讨诱导TLS作为肿瘤治疗手段的应用潜能。

Research on the Different Frequencies of Transcutaneous Electrical Acupoint Stimulation for Postpartum Pelvic Girdle Pain

Objective:To observe the clinical effect of different frequencies of transcutaneous electrical acupoint stimulation in treating postpartum pelvic girdle pain and promoting postpartum rehabilitation.Methods:From January to September 2022,300 patients with pelvic girdle pain after spontaneous delivery in a hospital in Shaanxi Province were selected and randomly divided into three groups,low frequency,high frequency,and alternating frequency,with 100 cases in each group.In addition to routine postpartum care and psychological counseling,the three groups received transcutaneous electrical acupoint stimulation at low-frequency(2 Hz,)high-frequency(100 Hz),and alternating frequency(2/100 Hz),respectively.The differences in initial pain,pain scores before and after treatment,satisfaction with analgesic effect,and postpartum rehabilitation effect were evaluated among the three groups of patients.Results:There was a significant correlation between maternal age and postpartum pelvic girdle pain(P<0.001),but no correlation was observed between newborn birth weight and postpartum pelvic girdle pain(P>0.05).After 1d/2d of treatment,the pain scores and rehabilitation effect of patients in the alternating-frequency group and low-frequency group were significantly better than those in the high-frequency group,and the postpartum curative effect of patients in the alternating-frequency group was the best,followed by the low-frequency group,and the high-frequency group;the differences were statistically significant(P<0.001).Among the three groups,the alternating-frequency group had the highest satisfaction with the analgesic effect and the highest rate of selecting the same analgesic regimen the next time;the differences were statistically significant(P<0.001).Conclusion:Transcutaneous electrical acupoint stimulation at different frequencies is safe and effective in treating postpartum pelvic girdle pain and beneficial to postpartum rehabilitation.Sparse-dense wave stimulation is effective in treating postpartum pelvic girdle pain.It has the best effect in promoting postpartum rehabilitation and the highest patient satisfaction.Therefore,its application in clinical practice is highly recommended.

Effect of Case Management for Patients with Gestational Diabetes

Objective:To explore the effect of allocating case managers for gestational diabetes patients.Methods:200 patients with gestational diabetes mellitus from December 2021 to December 2022 were included in this study,and the collection period.They were divided into groups according to the interventions received.Each patient in the observation group was managed by a case manager,while the control group were managed with conventional methods without the supervision of a case manager.There were 100 cases in each group,and the curative effects of the two groups were compared.Results:The fasting blood glucose and 2-hour postprandial blood glucose in the observation group were significantly lower than those of the control group(P<0.05).The re-admission rate of patients due to poor blood sugar control in the observation group was lower than that in the control group(P<0.05).The pregnancy outcome of the observation group was better than that of the control group(P<0.05).Conclusion:Case management of gestational diabetes can not only control the blood glucose of pregnant women,but also improve pregnancy outcomes.

An easily recoverable thermo-sensitive polyelectrolyte as draw agent for forward osmosis process

As a potential solution to the crises of energy and resources, forward osmosis(FO) has been limited by the development of draw agents. An ideal draw agent should be able to generate high osmotic pressure and can be easily recovered. In this study, a thermo-sensitive polyelectrolyte of poly(N-isopropylacrylamide-co-acrylic acid)(PNA)is developed as an efficient draw agent, and two easy and simple methods are proposed to effectively recover the polyelectrolytes. After adjusting the pH value of polyelectrolyte solutions to around 6.0, the polyelectrolyte can generate relatively high osmotic pressure, and induce average water fluxes of 2.09 and 2.95 L·m^(-2)·h^(-1) during12 h FO processes when the polyelectrolyte concentrations are 0.20 and 0.38 g·ml^(-1) respectively. After acidifying and heating to 70 °C, the PNA-10 polyelectrolyte can aggregate together because of hydrophobic association and separate from water, so it can be easily recovered by either simple centrifugation or gravitational sedimentation. The recovery ratios of PNA-10 polyelectrolyte in both methods are as high as 89%, and the recovered polyelectrolytes can be reused with almost the same FO performance as fresh ones. The results in this study provide valuable guidance for designing efficient and easily recoverable draw agents for FO processes.

Alterations in DNA damage response and repair genes as potential biomarkers for immune checkpoint blockade in gastrointestinal cancer

Objective:Immune checkpoint inhibitors(ICIs)have achieved remarkable results in cancer treatments.However,there is no effective predictive biomarker for gastrointestinal(GI)cancer.Methods:We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the Memorial Sloan Kettering Cancer Center cohort(MSK-GI,n=227),the Janjigian cohort(n=40),and the Peking University Cancer Hospital&Institute cohort(PUCH,n=80)to determine the possible associations between DNA damage response and repair(DDR)gene mutations and clinical outcomes.Data from The Cancer Genome Atlas database were analyzed to determine the possible correlations between DDR gene mutations and the tumor microenvironment.Results:In the MSK cohort,the presence of≥2 DDR gene mutations was correlated with prolonged overall survival(OS).The Janjigian and PUCH cohorts further confirmed that subgroups with≥2 DDR gene mutations displayed a prolonged OS and a higher durable clinical benefit.Furthermore,the DDR gene mutation load could be considered as an independent prognostic factor,and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs.Mechanistically,we showed that the presence of≥2 DDR gene mutations was correlated with higher levels of tumor mutation burden,neoantigen,and T cell infiltration.Conclusions:The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs,which could serve as a potential biomarker to guide patient selection for immunotherapy.

Advances in Studies on Treatment of Chronic Renal Failure with Ethnic Medicines

At present, the incidence of the chronic renal failure(CRF) is on the rise, and ethnic medicines have made significant achievements in the CRF treatment. In view of this, this paper reviewed the progress of ethnic medicines in the CRF treatment, to provide certain references for the personalized treatment of the CRF. Finally, it came up with the new recommendations for proper development and utilization of ethnic medicines.

Bioimaging of Dissolvable Microneedle Arrays: Challenges and Opportunities

The emergence of microneedle arrays(MNAs)as a novel,simple,and minimally invasive administration approach largely addresses the challenges of traditional drug delivery.In particular,the dissolvable MNAs act as a promising,multifarious,and well-controlled platform for micro-nanotransport in medical research and cosmetic formulation applications.The effective delivery mostly depends on the behavior of the MNAs penetrated into the body,and accurate assessment is urgently needed.Advanced imaging technologies offer high sensitivity and resolution visualization of cross-scale,multidimensional,and multiparameter information,which can be used as an important aid for the evaluation and development of new MNAs.The combination of MNA technology and imaging can generate considerable new knowledge in a cost-effective manner with regards to the pharmacokinetics and bioavailability of active substances for the treatment of various diseases.In addition,noninvasive imaging techniques allow rapid,receptive assessment of transdermal penetration and drug deposition in various tissues,which could greatly facilitate the translation of experimental MNAs into clinical application.Relying on the recent promising development of bioimaging,this review is aimed at summarizing the current status,challenges,and future perspective on in vivo assessment of MNA drug delivery by various imaging technologies.

Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis

Background:Evidence has suggested that cytokine storms may be associated with T cell exhaustion(TEX)in COVID-19.However,the interaction mechanism between cytokine storms and TEX remains unclear.Methods:With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis,we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy people.We observed a novel subset of severely exhausted CD8 T cells(Exh T_CD8)that co-expressed multiple inhibitory receptors,and two macrophage subclasses that were the main source of cytokine storms in bronchoalveolar.Results:Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe COVID-19.Cell–cell communication analysis indicated that cytokines(e.g.CXCL10,CXCL11,CXCL2,CCL2,and CCL3)released by macrophages acted as ligands and significantly interacted with inhibitory receptors(e.g.CXCR3,DPP4,CCR1,CCR2,and CCR5)expressed by Exh T_CD8.These interactions formed the cytokine–receptor axes,which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell carcinoma.Conclusions:Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in COVID19.Blocking cytokine-receptor axes may reverse TEX.Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.

A Concentric Array for Generating Multimode OAM Waves

For the problem of multiplexing multimodal vortex electromagnetic waves,a double-ring concentric uniform circular array(CUCA)consisting of 12 circularly polarized antennas(4 inner rings and 8 outer rings)is proposed in this paper.A complex feeding network is solved by rotating the circularly polarized antennas at a certain angle.The antennas are rotationally symmetric and point to the center,generating orbital angular momentum(OAM)waves by feeding the same amplitude and phase signals.In addition,this paper combines millimeter wave(mm-wave)and ultra-wideband(UWB)with OAM.The proposed antenna array can generate OAM beams at 30∼40 GHz with l=−1,−2.When l=−1 the relative bandwidth is 25.2% and the gain is 8.03 dBi;when l=−2 the relative bandwidth is 27.7% and the gain is 9.43 dBi.The analysis of simulation results shows that the antenna array has UWB performance,good gain,and a standard spiral phase distribution,which can provide some practical significance for modal multiplexing of mm-wave band OAM.

Highly-efficient CoRuO_(x)nanocatalysts for acidic oxygen evolution:The merit of optimum ordering degree of carbon nanotube support

Hydrogen production from proton exchange membrane water electrolysis is constrained by the sluggish kinetics of the anodic oxygen evolution reaction.RuO_(2)has attracted considerable attention due to its low reaction overpotential,but its inferior stability remains a major challenge.Herein,a strategy is proposed to enhance the catalytic activity and stability of CoRuOx nanoparticles by doping Co and regulating the ordering degree of carbon nanotubes(CNTs)by air annealing.It was found that the CoRuOx@CNTs-300 catalyst exhibited the best catalytic activity and stability when the annealing temperature was 300°C.At the current density of 10 mA cm−2,the overpotential of this catalyst was only 201 mV,which was nearly 100 mV lower than that of commercial RuO_(2)(300 mV).Surprisingly,there was no significant increase in the overpotential when tested at a current density of 10 mA cm−2 for 50 h.The density functional theory calculations indicate that the high activity of the catalyst is due to the electronic coupling of CoRuOx nanoparticles and CNTs,and that the introduction of Co and CNTs improves the electronic structure and solvation energies of the Ru in the active site,dramatically increasing the structural stability.

The clinical characteristics and risk factors for necrotizing soft tissue infection in children

Importance:Necrotizing soft tissue infection(NSTI)is a serious infectious disease.However,the early clinical manifestations and indicators of NSTI in children are still unclear.Objective:The purpose of this study was to analyze the clinical characteristics and risk factors of NSTI in pediatric patients.Methods:A total of 127 children with skin and soft tissue infection(SSTI)were treated at our hospital and divided into two groups:the NSTI group and the non-NSTI group,based on their discharge diagnosis from January 2011 to December 2022.Then,we collected and analyzed the clinical characteristics and risk factors of all patients,including sex and age,disease inducement,admission temperature,local skin manifestations,infection site,the presence of sepsis,bacterial culture,and laboratory indicators.Results:In our study,there was a statistical difference in the age distribution and disease inducement between NSTI and non-NSTI groups.The occurrence of local skin manifestations(blisters/bullae and ecchymosis)and the presence of sepsis significantly increased in the NSTI group compared to the non-NSTI group.Additionally,only the platelet count on laboratory tests was statistically different between the NSTI and non-NSTI groups.Finally,the logistic regression analysis suggested that local skin manifestations such as blisters/bullae,and ecchymosis,as well as the presence of sepsis,were identified as risk factors for NSTI.Interpretation:Children with SSTI and skin manifestations such as blisters/bullae,ecchymosis,and the presence of sepsis are at a higher risk of developing NSTI.These symptoms serve as useful indicators for early detection of NSTI.

Clinical efficacy and identification of factors confer resistance to afatinib(tyrosine kinase inhibitor)in EGFR-overexpressing esophageal squamous cell carcinoma

Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival benefits.Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC.This proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity profile.Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR expression.Notably,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment.Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.