Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients

Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and tumors.Therefore,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in HCC.Due to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various pathways.In recent years,the systematic treatment of HCC has gradually come out of the dilemma.In addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of HCC.At present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese patients.Therefore,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide concern.This review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy strategy;and(6)Shortcomings of immunotherapy.

哮喘患者病耻感现状及其影响因素分析

目的调查哮喘患者病耻感现状及其影响因素。方法采用便利抽样法,选取2022年9月15日至2023年2月15日在徐州医科大学附属医院就诊的哮喘患者为研究对象。采用一般资料调查表、中文版慢性疾病病耻感量表、社会支持评定量表、一般自我效能量表对哮喘患者进行问卷调查,分析其病耻感的影响因素。结果共纳入哮喘患者145例。患者的病耻感得分为(50.26±24.38)分。Pearson相关分析显示,社会支持总分、客观支持、主观支持、自我效能与病耻感总分均呈负相关(P<0.05);不同性别、职业、人均月收入、运动情况、病史,是否规律服药、是否有诱因的病耻感总分差异具有统计学意义(P<0.05);性别、人均月收入、社会支持为哮喘患者病耻感的独立影响因素(P<0.05)。结论哮喘患者病耻感处于中等水平,应重点关注男性、低收入及低社会支持等高危因素人群,降低哮喘患者病耻感水平。

Müller细胞在特发性黄斑裂孔形成及愈合机制中的研究进展

特发性黄斑裂孔(IMH)是指发病原因不明的黄斑区视网膜神经上皮层组织缺损。目前玻璃体切除联合内界膜剥除术已成为治疗IMH常规术式,可使大部分IMH患者达到解剖愈合,但愈合机制仍不明确。近年来,神经胶质细胞的激活在神经系统损伤和疾病病理过程中的作用日益受到人们重视,几乎所有神经系统(包括视网膜)的损伤和疾病都伴随着神经胶质细胞的激活;Müller细胞是人视网膜主要的一类神经胶质细胞,在解剖和功能上与视网膜各层神经元的胞体和突起有着广泛联系,对神经元起支持、营养及信息传导作用,众多研究表明Müller细胞激活并增殖在闭合黄斑裂孔(MH)中起主导作用,本文就Müller细胞在IMH形成和愈合过程及相关机制中的作用予以综述。

Pneumocystis jiroveci pneumonia after total hip arthroplasty in a dermatomyositis patient:A case report

BACKGROUND Pneumocystis jiroveci pneumonia(PJP)is a serious opportunistic infection that occurs mostly in patients with immunodeficiency and long-term immunosuppressive therapy.In non-human immunodeficiency virus-infected patients,the most important risk factor for PJP is the use of glucocorticoids in combination with other immunosuppressive treatments.The management of glucocorticoids during the perioperative period in patients with dermatomyositis requires special care.CASE SUMMARY We report a case of PJP in the perioperative period.A 61-year-old woman with a history of anti-melanoma differentiation-associated gene 5(MDA5)-positive dermatomyositis and interstitial pneumonia was administered with long-term oral methylprednisolone and cyclosporine.The patient underwent right total hip arthroplasty in the orthopaedic department for bilateral osteonecrosis of the femoral head.She was given intravenous drip hydrocortisone before anesthesia and on the first day after surgery and resumed oral methylprednisolone on the second postoperative day.On the fifth day after surgery,the patient suddenly developed dyspnea.The computed tomography scan showed diffuse grid shadows and ground glass shadows in both lungs.Polymerase chain reaction testing of bronchoalveolar lavage fluid was positive for Pneumocystis jiroveci.The patient was eventually diagnosed with PJP and was administered with oral trimethoprim-sulfamethoxazole.At the 6-mo review,there was no recurrence or progression.CONCLUSION Continued perioperative glucocorticoid use in patients with anti-MDA5-positive dermatomyositis may increase the risk of PJP.

Spherical Polyelectrolyte Brush Nanoreactor:Preparation of Hollow TiO_(2) Nanospheres and Characterization by Small Angle X-Ray Scattering

Titanium dioxide(TiO_(2))hollow nanoparticles present significant potential for photocatalytic applications while their straightforward preparation with precise structure control is still challenging.This work reports the approach to preparing tunable hollow TiO_(2) nanospheres by utilization of spherical polyelectrolyte brushes(SPB)as nanoreactors and templates.During the preparation,the evolution of the structure was characterized by small angle X-ray scattering(SAXS),and in combination with dynamic light scattering and transmission electron microscopy.The formation of TiO_(2) shell within the brush(SPB@TiO_(2))is confirmed by the significant increase of the electron density,and its internal structure has been analyzed by fitting SAXS data,which can be influenced by Titanium precursors and ammonia concentration.After calcining SPB@TiO_(2) in a muffle furnace,hollow TiO_(2) nanospheres are produced,and their transition to the anatase crystal form is triggered,as confirmed by X-ray diffraction analysis.Utilizing the advantages of their hollow structure,these TiO_(2) nanospheres exhibit exceptional catalytic degradation efficiency of methylene blue(MB),tetracycline(TC),and 2,4-dichlorophenoxyacetic acid(2,4-D),and also demonstrate excellent recyclability.

Quasi-two-body decays B_(c)→D^(*)h→Dπh in perturbative QCD

In this work,we investigate the quasi-two-body decays B_(c)→D^(*)h→Dπhwithh=(K^(0),π^(0),η,η′)using the perturbative QCD(PQCD)approach.The description of final state interactions of the Dπpair is achieved through the two-meson distribution amplitudes(DAs),which are normalized to the time-like form factor.The PQCD predictions on the branching ratios of the quasi-two-body decays B_(c)→D^(*)h→Dπh show an obvious hierarchy:Br(B^(+)_(c)→D^(∗+)K^(0)→D^(0)π^(+)K^(0))=(5.22^(+0.86)_(-0.74))×10^(-6),Br(B^(+)_(c)→D^(∗+)π^(0)→D^(0)π^(+)π^(0))=(0.93±0.26)×10^(-7),Br(B^(+)_(c)→D^(∗+)η→D^(0)π^(+)η)=(2.83^(+0.59)_(-0.52))×10^(-8)and Br(B^(+)_(c)→D^(∗+)η′→D^(0)π^(+)η′)=(1.89+0.40-0.36)×10^(-8).From the invariant mass m Dπ-dependence of the decay spectrum for each channel,one can find that the branching fraction is concentrated in a narrow region around the D*pole mass.Thus,one can obtain the branching ratios for the corresponding two-body decays B_(c)→D^(*+)h under the narrow-width approximation.We find that the branching ratios of the decays B_(c)→D^(*+)h are consistent with the previous PQCD calculations within errors.These predictions will be tested in future experiments.

Insights into the nature of X(3872)through B meson decays

We study the Bc,u,d→X(3872)P decays in the perturbative QCD(PQCD)approach,involving the puzzling resonance X(3872),where P represents a light pseudoscalar meson(K orπ).Assuming X(3872)to be a 1++charmonium state,we obtain the following results.(a)The branching ratios of the Bc+→X(3872)π+and Bc+→X(3872)K+decays are consistent with the results predicted by the covariant light-front approach within errors;however,they are larger than those given by the generalized factorization approach.(b)The branching ratio of the B+→X(3872)K+decay is predicted as(3.8-1.0+1.1)×10-4,which is smaller than the previous PQCD calculation result but still slightly larger than the upper limits set by Belle and BaBar.Hence,we suggest that the B0,+→X(3872)K0,+decays should be precisely measured by the LHCb and Belle II experiments to help probe the inner structure of X(3872).(c)Compared with the Bu,d→X(3872)K decays,the Bu,d→X(3872)πdecays have significantly smaller branching ratios,which drop to values as low as 10-6.(d)The direct CP violations of these considered decays are small(10-3~10-2)because the penguin contributions are loop suppressed compared to the tree contributions.The mixing-induced CP violation of the B→X(3872)K0S decay is highly consistent with the current world average value sin 2β=(69.9±1.7)%.Experimentally testing the results for the branching ratios and CP violations,including the implicit SU(3)and isospin symmetries of these decays,helps probe the nature of X(3872).

Pituitary stalk interruption syndrome complicated with liver cirrhosis:A case report

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare disorder,often characterized by delayed growth and development,short stature,and hypogonadism as the main clinical manifestations.It is not clear whether PSIS can lead to liver cirrhosis.CASE SUMMARY This paper reported a case of liver cirrhosis of unknown origin.The patient was admitted to Beijing Ditan Hospital Affiliated to Capital Medical University in November 2023.The diagnosis of PSIS complicated with liver cirrhosis was established after a series of blood tests and pituitary magnetic resonance imaging examination.CONCLUSION We also reviewed the literature from both domestic and international sources to deepen the clinical understanding of PSIS in conjunction with liver cirrhosis among medical practitioners.

Genome-wide identification of chitin-binding proteins and characterization of BmCBP1 in the silkworm, Bombyx mori

The insect cuticle plays important roles in numerous physiological functions to protect the body from invasion of pathogens, physical injury and dehydration. In this report, we conducted a comprehensive genome-wide search for genes encoding proteins with peritrophin A-type (ChtBD2) chitin-binding domain (CBD) in the silkworm, Bombyx mori. One of these genes, which encodes the cuticle protein BmCBP1, was additionally cloned, and its expression and location during the process of development and molting in B. mori were investigated. In total, 46 protein-coding genes were identified in the silkworm genome, including those encoding 15 cuticle proteins analogous to peritrophins with one CBD (CPAP1s), nine cuticle proteins analogous to peritrophins with three CBD (CPAP3s), 15 peritrophic membrane proteins (PMPs), four chitinases, and three chitin deacetylases, which contained at least one ChtBD2 domain. Microarray analysis indicated that CPAP-encoding genes were widely expressed in various tissues, whereas PMP genes were highly expressed in the midgut. Quantitative polymerase chain reaction and western blotting showed that the cuticle protein BmCBP1 was highly expressed in the epidermis and head, particularly during molting and metamorphosis. An immunofluorescence study revealed that chitin co-localized with BmCBP1 at the epidermal surface during molting. Additionally, BmCBP1 was notably up-regulated by 20-hydroxyecdysone treatment. These results provide a genome-level view of the chitin-binding protein in silkworm and suggest that BmCBP1 participates in the formation of the new cuticle during molting.

Foldable-circuit-enabled miniaturized multifunctional sensor for smart digital dust

Smart dust,which refers to miniaturized,multifunctional sensor motes,would open up data acquisition opportunities for Internet of Things(IoT)and Environmental protection applications.However,critical obstacles remain challenging in the integration of high-density sensors,further miniaturization of device platforms,and reduction of cost.Here,we demonstrate the concept of smart digital dust to address these problems,the results of which combine the benefit of(i)maturity of complementary metal-oxide semiconductor(CMOS)processing approaches and(ii)unique form factors of emerging flex-ible electronics.As a prototype for smart digital dust,we present a millimeter-scale multifunctional optoelectronic sensor platform con-sisting of high-performance optoelectronic sensor cores and commer-cially available integrated-circuit components.The smart material-assisted optoelectronic sensing mechanism enables real-time,high-sensitivity hydrogen,temperature,and relative humidity(RH)sens-ing based on a single chip with ultralow power consumption.Such a microsystem presented here introduces a viable solution to the multi-functional sensing need of IoT and could serve as a building block for the rapidly evolving future framework of smart dust.

Divergent Synthesis of N-Heterocycles by Merging Borane- Mediated Cyclopropane Ring-Opening and Hydride Abstraction

Herein,we report the synthesis of N-heterocycles by borane-catalyzed dehydrogenative cyclization of 2-cyclopropyl-N,N-dimethyl-anilines.Borane-mediated cyclopropane ring-opening and borane-mediated hydride abstraction from an N-methyl group are the key steps.The substituent at the cyclopropyl unit was found to greatly influence the reaction pathway and thus determined the major reaction product.

Quasi-two-body B_((s))→K^(*)γ→Kπγ decays in the perturbative QCD approach

In this study,we investigate quasi-two-body B_((s))→K^(*)γ→Kπγ decays in the perturbative QCD approach.Two-meson distribution amplitudes are introduced to describe the final state interactions of the Kπpair,which involve time-like form factors and Gegenbauer polynomials.We calculate the CP averaged branching ratios of the B_((s))→K^(*)γ→Kπγ decays.Our results are in agreement with newly updated data measured by Belle Ⅱ.This suggests that it is more appropriate to analyze these quasi-two-body B decays in the three-body framework than the two-body framework.We also predict direct CP asymmetries for the considered decay modes and find that A_CP(B_(u,d)→K^(*)γ→Kπγ) is small and less than 1% in magnitude,whereas A_CP(B_(s)→K^(*)γ→Kπγ)is larger and can reach a few percent.Our predictions can be tested in future B meson experiments.