Development and verification of an ELISA method for detection of process-specific residual host protein in biological preparation / 中国生物制品学杂志

@#Objective To develop and verify a double-antibody sandwich ELISA method for the detection of process-specific E.coli residual protein in recombinant biological preparations.Methods Taking the production and purification process of glucagon-like peptide(GLP)expressed by E.coli as the specific process model,the same process was used to intercept the residual protein of empty E.coli(normal E.coli that does not express recombinant protein). One female New Zealand white rabbit and six female Kunming mice were immunized with the residual protein as the immunogen. Using the IgG antibody purified from rabbit immune serum as the coating antibody,mouse immune serum as the second sandwich antibody,and antimouse IgG-HRP as the enzyme-labeled secondary antibody,a double antibody sandwich ELISA method for process-specific residual protein of E.coli was established. The specificity,accuracy and precision of the method were verified,and the limit of detection(LOD)was determined. Simultaneously,the developed method and the commercial E.coli host protein residue detection kit were used to quantitatively determine the residual protein of purified GLP preparation.Results After a series of gradient dilution of process-specific residual protein with known concentration,the sensitivity of this ELISA method reached 338 pg/mL. No cross reaction occurred in the detection of CHO and yeast cell lysis protein by this method,the recoveries of samples with low,medium and high concentrations were all in the range of 80% — 120%,and the intra-assay and inter-assay CVs of the empty E.coli interception standard with low,medium and high concentrations were all less than15%. For the residual protein in GLP preparation,about 62% of the residual proteins were not detected by the commercial non-process-specific ELISA kit compared with the total amount of residual proteins detected by the developed method,and these residual proteins should be the process-specific residual proteins.Conclusion The double antibody sandwich ELISA method developed in this study has high sensitivity,strong specificity,good accuracy and precision for the detection of process-specific E.coli residual protein,which can meet the detection requirements that the residual protein is less than0. 01% — 0. 1% in biological preparations.

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.

Anticancer effect of parasites and its underlying mechanisms: a review / 中国血吸虫病防治杂志

Both parasitic diseases and cancers are disorders that seriously threaten human health. A strong correlation has been recently found between parasitic infections and cancers, and multiple species of parasites and their derived products have shown effective to suppress cancer development, progression and metastasis. Therefore, deciphering the interaction among parasites, cancers and hosts not only provides new insights into the development of cancer therapy, but also provides the basis for screening of parasites-derived active anticancer molecules. This review summarizes the latest advances in the anticancer activity of parasites and underlying mechanisms.

Investigation of the population diversity of intermediate host snails and crabs of Paragonimus along Jiulong River, Zhangjiang River and Dongxi River basins in southern Fujian Province / 中国血吸虫病防治杂志

Objective To investigate the population distribution of intermediate host snails and crabs of Paragonimus along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, so as to provide baseline data for researches on parasitic disease prevention and control and enlargement of samples in the parasitic resource bank. Methods A total of 23 villages in 8 counties (districts) along the Jiulong River, Zhangjiang River, and Dongxi River basins in Zhangzhou City, Fujian Province were selected as survey sites during the period from November 2020 through March 2023, and snail and freshwater crabs were sampled from 1 to 3 streams and ditches neighboring residential areas in each village. Morphological identification of snails was performed according to the external morphological characteristics of collected snail shells, and the unidentified snail species sampled from the natural foci of paragonimiasis in Yunxiao County were subjected to se-quence analysis of the mitochondrial cytochrome oxidase 1 (CO1) gene. The crab species was identified by observing the morphological characteristics of the terminal segment of the first pleopod of male crabs, and Paragonimus cercariae and metacercariae were detected in collected snails. Results The shells of the unidentified snails sampled from the natural foci of paragonimiasis in Yunxiao County were approximately 50 mm in height and 18 mm in width, thick and solid, long tower cone-shaped, and had 8 to 10 whorls. CO1 gene sequence analysis identified the snail species as Sulcospira hainanensis. A total of 6 freshwater snail species belonging to 5 genera within 3 families, identified 23 survey sites, including Semisulcospira libertina, Paludomus zhangchouensis and S. hainanensis that belonged to the Family Pleurceridae, Tricula fujianensis and T. huaanensis that belonged to the subfamily Triculinae, Family Pomatiopsidae, and Melanoides tuberculata (Family Thiaridae), and 11 species of freshwater crabs belonging to 5 genera within 2 families were identified, including Sinopotamon genus of S. jianglense, S. pinheense, and S. zhangzhouense, Huananpotamon genus of H. planopodum and H. zhangzhouense, Nanhaipotamon genus of N. huaanense and N. longhaiense, and Minpotamon genus of M. nasicum and M. auritum that belonged to the Family Potamidae, and Somanniathelphusa genus of S. huaanensis and S. zhangpuensis (Family Parathelphusidae). In addition, the prevalence of P. westermani cercariae infections was 0.08% (2/2 317) in P. zhangchouensis from Danyan Village in Changtai District and 0.09% (1/1 039) in S. hainanensis from Jinkeng Village in Yunxiao County, and the prevalence of P. westermani metacercariae infections was 25.81% (8/31) in S. jianglense from Danyan Village in Changtai District, and 26.31% (5/19) in S. zhangzhouense from Jinkeng Village in Yunxiao County, respectively. Conclusions There is a population diversity in the intermediate host snails and crabs along the Jiulongjiang River, Zhangjiang River, and Dongxi River basins in Bopingling Mountain, southern Fujian Province, and P. zhangzhouensis and S. hainanensis are, for the first time, confirmed as the first intermediate hosts of P. westermani.

Preparation of the first national reference standard for determination of HEK293 cell DNA content / 中国生物制品学杂志

@#Objective To prepare a national reference standard for the quantification of HEK293 cell DNA content,so as to provide a support for the determination of residual DNA in HEK293 cells in the industry.Methods HEK293 cell DNA prepared using Genomic-tip 500/G and genomic DNA purification reagents was used as source materials,and the purity and content were assessed using ultraviolet spectrophotometry and agarose gel electrophoresis.After dilution to approximately 100 ng/μL,the DNA was aliquoted at 160 μL/tube.Five different laboratories were organized for collaborative calibration by using ultraviolet spectrophotometry, and the stability and applicability were evaluated.Results The HEK293 cell DNA national reference standard exhibited A_(260)/A_(280) ratios between 1.8 and 2.0 and displayed a single band on electrophoresis,meeting the specified criteria.Collaborative calibration across five laboratories yielded 78 valid data points with an average content of 104.8 ng/μL,a relative standard deviation(RSD) of 4.2%.The 95% confidence interval for the mean was 103.8—105.8 ng/μL,and the 95% reference range for single measurements was 96.0—113.6 ng/μL.The average confidence limit rate was 1.0%,and the recommended storage condition was-80 ℃.Applicability studies were conducted using two different models of fluorescence quantitative PCR instruments.The reference standard exhibited good applicability within the range of 0.3—3 000 pg/reaction,with amplification efficiencies of 101% and 95%,and R~2 values of 0.999 2 and 0.999 5 for the standard curves,respectively.Conclusion This batch of HEK293 cell DNA national reference standard meets all required specifications and can be utilized as a national reference standard for fluorescence quantitative PCR detection,with a certified content of 104.8 ng/μL,assigned batch number 270039-202301.

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

ABSTRACT Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and Method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

Dentistry consensus on HSCT - Part III: Special topics - Dentistry on HSCT

ABSTRACT Patients undergoing hematopoietic stem cell transplantation (HSCT) might present acute and late toxicities and the oral tissues are frequently affected. With the survival increasing, patients show late and long-term morbidities, and there is an important association between the general and the oral health. The first and second parts of this Consensus have showed the importance of the adequacy of oral health in the pre-HSCT, and the main alterations and oral care during the period of admission for HSCT. This third part aims to review specific themes of post-HSCT dental care, such as graft-versus-host disease (GVHD) and the pediatric patient. It also aims to review pertinent subjects, both during the HSCT period and post-HSCT, concerning quality of life, pain, cost-effectiveness, and remote care. Based on this review, it is evident the importance of the work of the dental surgeon (DS) in the follow-up and treatment of the HSCT patient, always collaborating with the whole multidisciplinary team.

Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease

Purpose: The current study was carried out to evaluate the clinical features and management outcomes of dry eye disease (DED) in chronic ocular GvHD following allogenic hematopoietic stem cell transplantation (HSCT). Methods: A retrospective review of consecutive patients diagnosed with chronic ocular GvHD between 2011 and 2020 was performed at a tertiary eye care network. Multi?variate regression analysis was carried out for identifying risk factors associated with progressive disease. Results: A total of 34 patients (68 eyes) with a median age of 33 years [inter?quartile range (IQR) 23–40.5] were studied. The most common indication for HSCT was acute lymphocytic leukemia (26%). Ocular GvHD developed at a median of 2 years (IQR 1–5.5 years) after HSCT. Aqueous tear deficiency was present in 71% of the eyes, of which 84% had a Schirmer value of <5 mm. The median visual acuity at presentation and that after a median follow? up of 6.9 months were comparable at 0.1 log minimum angle of resolution (logMAR) (P = 0.97). Topical immunosuppression was required in 88% of cases, and with this, improvement in corneal (53%, P = 0.003) and conjunctival staining scores (45%, P = 0.43) was noted. A progressive disease was present in 32% with persistent epithelial defects being the most common complication. Grade 2 conjunctival hyperemia [odds ratio (OR): 2.6; P = 0.01] and Schirmer’s value <5 mm (OR: 2.7; P = 0.03) were found to be associated with progressive disease. Conclusion: Aqueous deficient DED is the most common ocular manifestation of chronic ocular GvHD, and the risk of the disease progression is greater in eyes with conjunctival hyperemia and severe aqueous deficiency. Awareness among ophthalmologists of this entity is essential for its timely detection and optimal management.

Minimalist revision of Mesochorus Gravenhorst, 1829 (Hymenoptera: Ichneumonidae: Mesochorinae) from Área de Conservación Guanacaste, Costa Rica, with 158 new species and host records for 129 species / Revisión minimalista de Mesochorus Gravenhorst, 1829 (Hymenoptera: Ichneumonidae: Mesochorinae) del Área de Conservación Guanacaste, Costa Rica, con 158 especies nuevas y registros de hospedantes para 129 especies

Introduction: Species of Mesochorus are found worldwide and members of this genus are primarily hyperparasitoids of Ichneumonoidea and Tachinidae. Objectives: To describe species of Costa Rican Mesochorus reared from caterpillars and to a lesser extent Malaise-trapped. Methods: The species are diagnosed by COI mtDNA barcodes, morphological inspection, and host data. A suite of images and host data (plant, caterpillar, and primary parasitoid) are provided for each species. Results: A total of 158 new species of Mesochorus. Sharkey is the taxonomic authority for all. Conclusions: This demonstrates a practical application of DNA barcoding that can be applied to the masses of undescribed neotropical insect species in hyperdiverse groups.

Introducción: Las especies de Mesochorus se encuentran en todo el mundo y los miembros de este género son principalmente hiperparasitoides de las familias Ichneumonoidea y Tachinidae. Objetivos: Describir las especies de Mesochorus costarricenses obtenidas de orugas y en menor medida por trampas Malaise. Métodos: Las especies se diagnosticaron mediante el uso de código de barra molecular por COI del ADNmt, inspección morfológica y datos del huésped. Se proporciona un conjunto de imágenes y datos de los huéspedes (planta, oruga y parasitoide primario) para cada especie. Resultados: Se encontró un total de 158 nuevas especies de Mesochorus. Sharkey es la autoridad taxonómica para todas las especies. Conclusiones: Se demuestra una aplicación práctica del código de barras de ADN que se puede aplicar a grandes cantidades de especies de insectos neotropicales no descritas para grupos hiperdiversos.

Nocardiosis pulmonar y del sistema nervioso central: el alcoholismo como factor de inmunocompromiso / Pulmonary and central nervous system nocardiosis: Alcoholism as an immunocompromising factor

La nocardiosis es una enfermedad de distribución mundial; de forma habitual se encuentra en zonas tropicales y afecta principalmente a pacientes inmunocomprometidos, sin embargo, también existen casos reportados de infección en personas inmunocompetentes. Esta infección es causada por actinomicetos del género Nocardia spp. que son bacterias Gram positivas, saprófitos ambientales. Aunque la exposición a Nocardia spp. es casi universal, solo una pequeña fracción de las personas expuestas desarrollan la enfermedad. Se presenta el caso de un hombre de 47 años, sin dato de inmunosupresión, procedente de un área rural de Boyacá, que consultó por un cuadro clínico de cefalea intensa e intermitente, con parestesias y, finalmente, alteración del estado de conciencia. Se practicó una resonancia magnética cerebral, en la que se evidenció una lesión que ocupaba espacio de localización córtico-subcortical en la región fronto-témporo-parietal izquierda, con efecto compresivo y desplazamiento de las cavidades del sistema ventricular. Se sospechó, inicialmente, una lesión neoplásica o un absceso cerebral. El paciente fue sometido a una resección quirúrgica, y el cultivo de la lesión documentó Nocardia africana/nova; en estudios posteriores, se evidenció un posible foco pulmonar primario. Como único factor de riesgo en el paciente, se documentó alcoholismo. Completó seis semanas de tratamiento antibiótico intrahospitalario con evolución clínica y radiológica, y egresó con plan de un año de terapia antibiótica ambulatoria. Aunque la enfermedad por Nocardia spp. afecta principalmente a pacientes inmunocomprometidos, la "evidencia" clínica demuestra que este microorganismo también puede ser una amenaza para individuos sin los factores de riesgo tradicionales para inmunosupresión.

Nocardiosis is a disease with worldwide distribution. It is usually found in tropical areas and mainly affects immunocompromised patients, however, there are also cases where its infection has been reported in immunocompetent patients. This pathology is caused by bacteria known as Nocardia spp., which are gram-positive microorganisms and environmental saprophytes, and although exposure to Nocardia spp. is almost universal, only a small fraction of exposed people develops the disease. We present the case of a 47-year-old man, with no evidence of immunosuppression, from a rural area of Boyacá, who was admitted due to intense and intermittent headache accompanied by paresthesia and, finally, a decrease in consciousness. A brain magnetic resonance was performed and evidenced a fronto-temporo- occipital space-occupying lesion in the cortico-subcortical region with a compressive effect and displacement of the ventricular system cavities. It was suspected at first a neoplastic lesion or a brain abscess. The lesion was surgically resected, and its culture showed Nocardia africana/nova. In later studies a possible primary pulmonary focus was evidenced. Alcoholism was the only risk factor documented. The patient completed 6 weeks of hospital antibiotic treatment with favorable clinical and radiological evolution and was discharged with a 1-year plan of outpatient antibiotic therapy. Although Nocardia spp. mainly affects immunocompromised patients, evidence shows that this microorganism can also be a threat to individuals without traditional immunosuppression risk factors.

Development and verification of a quantitative real-time PCR method for determination of host cell DNA residues in inactivated SARS-CoV-2 vaccine(Vero cells) / 中国生物制品学杂志

@#Objective To develop and verify a quantitative real-time PCR method for determination of the content of host cell DNA residues in severe acute respiratory symptom coronavirus 2(SARS-CoV-2) inactivated vaccine(Vero cells),in order to better control the safety of products.Methods DNA was extracted from inactivated SARS-CoV-2 vaccine(Vero cells) bulk by magnetic bead separation method,and the DNA residues of host cells were quantitatively analyzed by probetype PCR.The linear range,repeatability,intermediate precision,quantitative limit,specificity,durability and accuracy of the developed method were verified,and the host cell DNA re sidues of 5 batches of inactivated SARS-CoV-2 vaccine(Vero cells)were determined by this method.Results DNA standard curve showed good linearity in the range of 300～0.003 pg/μL(each R~2> 0.99);Relative standard deviations(RSD) of repeatability and intermediate precision verification were less than 20%;The quantitative limit was 0.001 pg/μL;Sample dilution and purified liquid dilution had no interference to detection;The results of 60 min incubation at 53,55,57 ℃ and 56,60,64 min incubation at 55 ℃ showed no significant difference;The recoveries of accuracy verification were 79%～83%,RSD <5%.This method had good adaptability in detecting DNA residues in the bulk of inactivated SARS-CoV-2 vaccine(Vero cells).Conclusion The quantitative realtime PCR method for determination of host cell DNA residues in inactivated SARS-CoV-2 vaccine(Vero cells) has been successfully developed,of which the linearity and range,repeatability,intermediate precision,quantitative limit,specificity,durability and accuracy meet the acceptable standards,and are suitable for the detection and quality control of host cell DNA residues in inactivated SARS-CoV-2 vaccine(Vero cells).

Clinical observation of acupuncture with host-guest combination using Yuan-Primordial and Luo-Connecting points plus Tuina for the third lumbar transverse process syndrome / 针灸推拿医学（英文版）

Objective: To observe the effects of acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination plus Tuina (Chinese therapeutic massage) on the third lumbar transverse process syndrome. Methods: A total of 88 patients with the third lumbar transverse process syndrome were selected and divided into an observation group and a control group according to the random number table method, with 44 cases in each group. The control group was treated with Tuina, and the observation group was treated with additional acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination. The clinical efficacy of the two groups was compared after treatment. The changes in the scores of physical signs, Roland-Morris disability questionnaire (RMDQ), Oswestry disability index (ODI), Quebec back pain disability scale (QBPDS), and pain factors [including serum prostaglandin (PG) E2, neuropeptide Y (NPY), and matrix metalloproteinase-3 (MMP-3)] were observed. Results: After treatment, the total effective rate in the observation group was 93.2％, higher than 75.0％ in the control group; the difference between the two groups was statistically significant (P<0.05). Compared with those before treatment, the scores of physical signs and each low back pain scale, and the levels of serum pain factors in the two groups were decreased (P<0.05), and those in the observation group were lower than those in the control group (P<0.05). Conclusion: Acupuncture at Yuan-Primordial and Luo-Connecting points by host-guest combination plus Tuina is effective in the treatment of the third lumbar transverse process syndrome; it can improve the patient's physical signs, relieve low back pain, and reduce the levels of serum pain factors.

Study on the relationship between serum cytokines levels after chimeric antigen receptor (CAR)-T cell immunotherapy and the prognosis of bridged allogeneic hematopoietic stem cell transplantation in acute B lymphoblastic leukemia patients / 中华检验医学杂志

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Programmed cell death induced by Klebsiella pneumoniae infection / 中华微生物学和免疫学杂志

Klebsiella pneumoniae can cause a variety of infectious diseases, especially in immunocompromised population. The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae has greatly limited the choice of treatment for Klebsiella pneumoniae infection, and the exploration of new treatment strategies is imminent. In the process of infection, there is a complex interaction between the programmed cell death of host cells and the invasion of Klebsiella pneumoniae. This paper mainly reviewed the research progress in several mechanisms of programmed cell death such as pyroptosis, apoptosis, necroptosis and autophagy caused by Klebsiella pneumoniae.

Research advance of mesenchymal stem cell-derived exosomes in graft-versus-host disease / 中华器官移植杂志

Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewing differentiation, immunoactivity and anti-inflammatory potentials.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the most effective treatment for hematologic malignancies.However, the presence of graft-versus-host disease (GVHD) after transplantation has hindered the development of allo-HSCT.MSC-derived exosomes (MSC-exo) derived from mesenchymal stem cells have been confirmed to have broad therapeutic prospects in allo-HSCT and GVHD.This review focused upon immunomodulatory effects of MSC, biological activities of MSC-exo and research advances of MSC-exo on managing GVHD, aiming to provide new therapeutic rationales for GVHD in the future.

Symbiotic homeostasis of Staphylococcus epidermidis is associated with common skin disorders / 中华皮肤科杂志

Staphylococcus epidermidis can exhibit both protective and opportunistic pathogenic effects on the skin: on the one hand, it suppresses pathogenic bacteria and inflammation, assists the innate immune system of the skin, and maintains homeostasis of skin microenvironment; on the other hand, it exhibits pathogenic potential. How Staphylococcus epidermidis affects human skin conditions depends not only on itself, but also on the communication among it, the host immune system, other microorganisms and environment factors. The balance of this interaction is the symbiotic homeostasis of Staphylococcus epidermidis, and when the homeostasis is disrupted, a variety of skin diseases such as acne vulgaris, atopic dermatitis, rosacea and melanoma can occur. Factors affecting the symbiotic homeostasis of Staphylococcus epidermidis include environmental conditions such as temperature, oxygen content and nutrition, antibiotics, the number of other microorganisms, microecological diversity, etc. This review summarizes recent research progress in symbiotic homeostasis of Staphylococcus epidermidis.

Preliminary study of shear wave dispersion imaging in the evaluation of hepatic acute graft-versus-host disease / 中华超声影像学杂志

Objective:To investigate the feasibility of using shear wave dispersion (SWD) imaging in evaluating acute graft-versus-host disease (aGVHD) of the liver.Methods:A total of 42 Wistar rats were used as receptors and 10 Fischer 344 rats were used as donors for bone marrow transplantation to establish aGVHD models. Six rats were randomly selected every week for clinical observation and scoring. Then, ultrasonic SWD was performed to obtain shear wave speed (SWS) and shear wave dispersion slope (SWDS). Then, the histological characteristics were used as a reference standard, and the rats were divided into two groups: the group without aGVHD (nGVHD group) and the group with aGVHD. The differences in the clinical score and SWD values between the two groups were compared, the meaningful indexes were screened by binary Logistic regression analysis, and the joint prediction parameters were obtained. The ROC curve was plotted and the diagnostic efficiency was compared. The correlations between SWS, SWDS, clinical score and pathological grade were analyzed.Results:Clinical score, SWS, and SWDS in aGVHD group were higher than those in the nGVHD group (all P<0.05). The correlation between SWDS and pathological grade ( r=0.774, P<0.001) was higher than those between SWS, clinical score and pathological grade ( r=0.579, P=0.005; r=0.452, P=0.034). Logistic regression showed that SWDS was a significant indicator. In addition, the AUC values determined by SWDS and predictive parameters were (0.859, 0.886), which were significantly higher than the AUC of the clinical score (0.760, P<0.05). Conclusions:SWD imaging technology may become a promising method to evaluate hepatic aGVHD.

Research progress on sensitivity, resistance and mechanism of plague infected animals to Yersinia pestis / 中华地方病学杂志

The sensitivity and resistance of host animals to Yersinia pestis are different among species and regions, and the indicator animals have natural resistance to Yersinia pestis. This article reviews the research progress on sensitivity, resistance and mechanism of plague infected animals to Yersinia pestis, in order to help improve the ecological research of plague and the prevention and control of plague.

Host cell protein quantification workflow using optimized standards combined with data-independent acquisition mass spectrometry / 药物分析学报

Monitoring of host cell proteins(HCPs)during the manufacturing of monoclonal antibodies(mAb)has become a critical requirement to provide effective and safe drug products.Enzyme-linked immunosor-bent assays are still the gold standard methods for the quantification of protein impurities.However,this technique has several limitations and does,among others,not enable the precise identification of pro-teins.In this context,mass spectrometry(MS)became an alternative and orthogonal method that de-livers qualitative and quantitative information on all identified HCPs.However,in order to be routinely implemented in biopharmaceutical companies,liquid chromatography-MS based methods still need to be standardized to provide highest sensitivity and robust and accurate quantification.Here,we present a promising MS-based analytical workflow coupling the use of an innovative quantification standard,the HCP Profiler solution,with a spectral library-based data-independent acquisition(DIA)method and strict data validation criteria.The performances of the HCP Profiler solution were compared to more con-ventional standard protein spikes and the DIA approach was benchmarked against a classical data-dependent acquisition on a series of samples produced at various stages of the manufacturing process.While we also explored spectral library-free DIA interpretation,the spectral library-based approach still showed highest accuracy and reproducibility(coefficients of variation＜10％)with a sensitivity down to the sub-ng/mg mAb level.Thus,this workflow is today mature to be used as a robust and straightforward method to support mAb manufacturing process developments and drug products quality control.

Establishment an aggregation-induced emission vesicle material based on supramolecular host-guest chemical assembly for siRNA delivery and study on its toxicity to tumor cells / 国际生物医学工程杂志

Objective:To establish an aggregation-induced emission vesicle material based on supramolecular host-guest chemical assembly (AIE-HG-Vesicle) for siRNA delivery and fluorescence imaging, and to explore its uptake effect by tumor cells and siRNA-based cell killing effect.Methods:By synthesizing β-cyclodextrin modified with polyethyleneimine dendrimer (H-β-CD-dendrimer) as a host compound and a Bola type adamantane containing tetrastyrene AIE group (G-Ada-AIE) as a guest compound, the nanovesicle material was prepared by a supramolecular host-guest self-assembly process for loading siRNA. The morphology and size of the materials were tested by transmission electron microscopy and the dynamic light scattering method. The aggregation-induced luminescence properties of the materials were investigated by fluorescence spectrophotometry. The loading effect of the material on siRNA was investigated by gel retardation experiments. The delivery effect of siRNA-loaded AIE-HG-Vesicle vesicles in tumor cells was observed by a confocal laser scanning microscope. The killing effect of siRNA-loaded AIE-HG-Vesicle vesicles on tumor cells was tested by an MTT assay.Results:The prepared host-guest compounds can be assembled into vesicles with a size of about 100 nm and wall thickness of 9 nm in solution, and the positively charged vesicles on the surface can efficiently load siRNA. The siRNA-loaded AIE-HG-Vesicle vesicles can deliver siRNA into HeLa tumor cells and can be observed through aggregation-induced luminescence. The siRNA-loaded vesicles have an obvious killing effect on HeLa tumor cells.Conclusions:A vesicle material with aggregation-induced luminescence properties was prepared by a method based on supramolecular host-guest chemical assembly, which can be used to deliver siRNA. The material has fluorescence imaging and siRNA-based tumor cytotoxic effects and is expected to be applied to tumor treatment in vivo.