Research progress on quantitative detection methods of lateral flow immunochromatography assay / 药学实践与服务

Lateral flow immunochromatography assay is a new instantaneous detection technology that employs a chromatographic membrane and labeling materials for detection. This detection technology is convenient, fast, and inexpensive, and is therefore widely used in a number of different fields, such as biomedicine, disease detection, food safety, environmental protection, and so on. Traditional lateral flow immunochromatography assay relied on visual observation and provided only qualitative or semi-quantitative results. By utilizing various types of markers and sensitive detection devices, lateral flow immunochromatography assay enables quantitative and multi-component detection of the analytes. The research progress on the lateral flow immunoassay detection system and its current applications in the context of recognition elements, labeling materials, and detection instruments were reviewed in this paper.

Simultaneous GC-MS determination of sixteen pesticide residues and safety assessment for Lycii Fructus / 中成药

AIM To establish a GC-MS method for the simultaneous content determination of sixteen pesticide residues in Lycii Fructus and perform safety assessment.METHODS The analysis was performed on DB-5MS chromatographic column(30 m×0.25 mm,0.25 μm)subjected to the programmed heating,with splitless injection of 1.0 μL dissolved sample at a flowing rate of 1.0 mL/min.Other parameters were as follows:injection port temperature of 250℃,electron impact ionization(EI),electron energy of 70 eV;ion source temperature of 230℃,multi-reaction monitoring mode,and collision gas.of high-purity N2.Pesticide residues with relatively high dietary risk were analyzed and discussed with regard to residue levels,dietary intake risk,risk ranking and cumulative exposure assessment.RESULTS Sixteen pesticides showed good linear relationships within their own ranges(r≥0.994 4),whose average recoveries were 70%-114%,with the RSDs of less than 2%.The highest average cyfluthrin residue of 0.999 2 mg/kg in Lycii Fructus of production regions and the highest average cypermethrin residue of 0.088 4 mg/kg in Lycii Fructus commodities were both detected.In Lycii Fructus of production regions with chronic hazard index(HI)value of 0.012 9 and acute HI value of 0.065 5 and their commodities with chronic HI of 0.001 2 and acute HI of 0.005 4,the pesticide residue of cypermethrin was the leading cause of chronic and acute dietary risk,and additionally,pyridaben within maximum residue limit(MRL)was the only detectectable highly toxic pesticide among the other most concerning pestcides of deltamethrin,pyridaben,chlorpyrifos,dichlorvos and methidathion.CONCLUSION There exist pesticide residues within MRL values in some samples of Lycii Fructus and the use of cypermethrin should be well-controlled.

Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center / 中华妇产科杂志

Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.

Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis / 中国当代儿科杂志

OBJECTIVES@#To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC).@*METHODS@#Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota.@*RESULTS@#Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora.@*CONCLUSIONS@#Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

Causes of HLA-A2 reactive antibodies and analysis of their eplets / 中国输血杂志

【Objective】 To analyze differences of eplets between the patient who generated HLA allele-specific antibodies after platelet transfusion with donors. 【Methods】 The HLA genotypes of the patient and donors were detected by PCR-SBT, and the Luminex single antigen beads coating was used to screen HLA-Ⅰ antibodies in the patient’s serum. HLA Matchmaker was utilized to analyze different amino acids and eplets. 【Results】 The patient carried HLA-A*02∶03 allele, and HLA-A2 antibodies were found in his serum after platelet transfusion (A*02∶01, A*02∶06, and A*02∶07). Sequence alignment showed that the patient′s A*02∶03 has a difference in position 149, which resulted in a different eplet between A*02∶03 and A*02∶01, A*02∶06, A*02∶07 and then induced the production of antibodies. 【Conclusion】 HLA antibodies are specific for HLA epitopes that have structural differences due to amino acid differences between HLA alleles, suggesting that high-resolution typing of HLA-A, -B need to be conducted in patients and donors, and the acceptable mismatch of HLA should be determined based on epitopes rather than antigens, so as to reduce alloimmune response and improve platelet count after transfusion.

Screening of anti-SARS-CoV-2 ligands from Chinese herbs based on a dual-target surface plasmon resonance biosensor / 药学学报

The epidemic of COVID-19 has brought great challenges to the global public health prevention and control system combined with clinical diagnosis and treatment system, and it makes the development of effective antiviral drugs an important task in current pharmaceutical research. Traditional Chinese medicine (TCM) has played an important role in the prevention and control of COVID-19. Due to its numerous chemical components and various structural types, TCM becomes a natural library for searching for lead compounds against SARS-CoV-2. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed for S protein receptor binding domain (SRBD) and angiotensin converting enzyme 2 (ACE2) which are two key proteins in the process of SARS-CoV-2 invading cells according to characteristics of synergistic effects of multiple components and comprehensive regulation of multiple targets of TCM. The SPR biosensor was applied to screen and identify active components from six TCMs, and daidzin from Puerariae Lobatae Radix was identified to bind with SRBD and ACE2. The affinity constant (KD) of daidzin and ACE2 was 5.18 μmol·L-1 through the SPR affinity assay. Competitive ELISA assay showed that daidzin could inhibit the binding of SRBD and ACE2, and the inhibition rate of daidzin (20 μmol·L-1) was 38.6%. Molecular docking experiments further confirmed that daidzin had the best binding near the binding region of SRBD-ACE2 complex. This study shows that the dual-target SPR screening system is accurate and efficient, and is particularly suitable for screening of complex drug systems and effective substances study of TCM. It provides a material basis for exploring the mechanism of TCM active constituents against SARS-CoV-2, and provides a source of lead compounds for the development of anti-SARS-CoV-2 drugs.

The fenrou zhijian theory in The Inner Canon of Huangdi and the stratified treatment of painful bi syndrome of meridian tendons / 中国针灸

The fenrou zhijian is defined as potential gap between different layers in the three-dimensional network structure formed by the twelve meridian tendons. Various pathological changes of the meridian tendons lead to the adhesion and closure of fenrou zhijian, causing abnormal mechanical conduction of the meridian tendon system, which in turn leads to painful bi syndrome of meridian tendons. As such, restarting the fenrou zhijian is the key to acupuncture treatment for painful bi syndrome of meridian tendons. Under the guidance of musculoskeletal ultrasound, the level and the angle of needle insertion of acupuncture at fenrou zhijian could be accurately controlled, the efficacy of acupuncture is improved.

Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix / 中华妇产科杂志

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

Clinical, genetic, and pathological analysis in 165 children with disorders of sex development / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD).@*METHODS@#A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022.@*RESULTS@#Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants.@*CONCLUSIONS@#Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Latest research progress on pathological mechanism of senile pruritus / 中华老年医学杂志

The pathological mechanism of the occurrence of elderly pruritus has not yet been fully elucidated.The changes in lipid composition between keratinocytes, incomplete structure of membrane filaggrin, decreased levels of natural moisturizing factors, changes in pH and decreased levels of estrogen can lead to impaired skin barrier function, and play an important role in the pathogenesis of skin pruritus.An inflammatory environment caused by immune aging, and neurological degenerative changes and pathological damage are also believed to influence the occurrence of senile pruritus.In addition, some systemic diseases are also closely related to the occurrence and development of pruritus in the elderly, such as chronic kidney disease, cholestatic diseases, diabetes, malignant tumors, etc.Further elucidation of the pathological mechanism of pruritus in the elderly can provide useful diagnosis and treatment ideas for the prevention and treatment of diseases.

Effect of early external diaphragm pacing on patients with mechanical ventilation / 中华急诊医学杂志

Objective:To investigate the effect of early external diaphragm pacing on the diaphragm function and prognosis of patients with mechanical ventilation.Methods:A total of 47 patients receiving invasive mechanical ventilation in the Emergency Intensive Care Unit of Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University) from October 2019 to July 2021 were selected and randomly divided into the treatment group ( n=23) and control group ( n=24). The patients in the control group received routine clinical treatment. On this basis, the treatment group received external diaphragm pacing treatment every day from the third day of mechanical ventilation until weaning, and was followed up to 30 days after discharge. The diaphragm thickness, diaphragm excursion, diaphragm thickening fraction, mechanical ventilation time, number of weaning failures, length of hospital stay and death toll were compared between the two groups. Results:Compared with the control group, the diaphragm thickness [(0.21±0.05) cm vs. (0.16±0.05) cm], diaphragm excursion [(1.38±0.37) cm vs. (1.11±0.48) cm], and diaphragm thickening fraction [26% (19%, 32%) vs. 18.5% (10.25%, 20%)] in the treatment group increased significantly (all P<0.05). The mechanical ventilation time was shorter in the treatment group [10 (7, 15) d vs. 13 (10.25, 19) d], and the difference was statistically significant ( P<0.05). There were no significant differences in the number of weaning failures (7 vs. 9), length of hospital stay [22 (15 , 30) d vs.. 24 (17.25, 34.25) d] and deaths (8 vs. 8) (all P>0.05). Conclusions:Early application of external diaphragm pacing can improve the diaphragm function of patients with mechanical ventilation, delay the decline in diaphragm function, increase diaphragm excursion and diaphragm thickening fraction, and shorten the mechanical ventilation time.

Clinical Characterization of Patients with Ovarian Mass Combined with Dysplasia of Secondary Sexual Characteristics / 中国医学科学院学报

Objective To investigate the clinical characteristics of preadolescent and adolescent female patients with ovarian mass combined with dysplasia of secondary sexual characteristics. Methods This study retrospectively analyzed 18 cases of ovarian mass combined with dysplasia of secondary sexual characteristics aged 0-19 years admitted to Peking Union Medical College Hospital from January 2012 to November 2019.By analyzing the clinical manifestations,surgical methods,postoperative pathology,therapies and prognosis of the cases,we summarized the diagnosis and treatment ideas. Results Among the 18 cases,7(7/18,38.9%)developed secondary sex signs before puberty,including 5 cases showing precocity(including 2 cases of juvenile granulosa cell tumor,1 case of gonadoblastoma,1 case of ovarian follicular cyst,and 1 case of 46,XY simple gonadal dysplasia combined with dysgerminoma)and 2 cases presenting masculine manifestations(1 case of steroid cell tumor and 1 case of sclerosing stromal tumor).The rest 11(11/18,61.1%)cases showed abnormal development of secondary sexual characteristics during puberty,including 8 cases with masculine manifestations or abnormal menstruation after menarche(7 cases with sex cord stromal cell tumor and 1 case with cystic granulosa cell tumor),2 cases with primary amenorrhea(1 case with androgen insensitivity syndrome combined with testicular sertoli cell tumor and 1 case with endometriosis cyst combined with reproductive tract malformation),and 1 case diagnosed as 46,XX gonadal dysplasia with serous cystadenoma and no secondary sexual development during puberty. Conclusions Sex hormone levels should be actively tested in the case of prepubertal secondary sexual characteristics appearing early,pubertal secondary sexual characteristics being abnormal(underdevelopment),and/or menstrual abnormalities.Imaging examination should be performed to exclude ovarian organic lesions,and chromosome karyotype analysis should be performed if necessary.The diagnosis of ovarian mass in preadolescent and adolescent females with related symptoms should first be alerted to cord stromal cell tumor.It is recommended to rule out the possibility of combined reproductive tract malformation in the adolescent patients with primary amenorrhea.Chromosome examination should be conducted to rule out the possibility of gonadal dysplasia in the adolescent patients with primary amenorrhea and/or no development of secondary sexual characteristics.

Research on Current Situation and Countermeasures of Public Health Emergency in a Rural Area of Hubei Province / 中国医学伦理学

Major public health emergencies have challenged the public health emergency response capacity of rural areas. Through the investigation and research on the epidemic prevention and control situation in a rural area in Hubei, 93 households were randomly sampled by questionnaire survey method, and 10 households were interviewed by the semi-structured interview method. The data were analyzed by cross-analysis and descriptive analysis. The results showed that the main body involved in epidemic prevention and control in rural areas was single, and the epidemic prevention and control measures mostly adopted simple measures such as closed management. It was difficult to implement epidemic prevention and control measures in the village. The village doctors assumed basic medical and health service functions but were not highly motivated. Sanitation facilities were lacking, but the social comprehensive publicity of epidemic prevention and control safety education and infectious disease prevention knowledge was effective. In the post-epidemic era, it is necessary to increase the public health and health awareness of rural residents through strengthen publicity, improve and optimize the rural public health system, build a rural public health community, and enhance village doctors’ professional quality, so as to promote the emergency response capacity of rural public health.

Screening of immune cell activators from Astragali Radix using a comprehensive two-dimensional NK-92MI cell membrane chromatography/C18 column/time-of-flight mass spectrometry system / 药物分析学报

Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.

Development of a surface plasmon resonance biosensor for accurate and sensitive quantitation of small molecules in blood samples / 药物分析学报

Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical appli-cations,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatography-ultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detec-tion was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day ac-curacies of SPR were 98％-114％and 110％-122％,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.

Effect of Buyi Pishen acupuncture on inflammatory factor and cartilage matrix in adjuvant arthritis rats / 中国针灸

OBJECTIVE@#To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA).@*METHODS@#A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method.@*RESULTS@#Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group.@*CONCLUSION@#Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.

Screening potential P-glycoprotein inhibitors by combination of a detergent-free membrane protein extraction with surface plasmon resonance biosensor

P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.

Research progress of cyclic peptides derived from phage display technology / 药学学报

Cyclic peptide drugs have gradually become an emerging research direction due to their some favorable properties such as high-efficiency binding affinity, high selectivity, lower toxicity, and stable metabolism. In recent years, the number of cyclic peptide drugs under clinical research has continued to increase. Unlike the previous cyclic peptide drugs, which were mostly derived from natural products and their derivatives, these cyclic peptide drugs are designed by genetically encoded display technologies which are based on rational design and in vitro evolution (such as BT1718, PTG-300, POL6326, etc). Among them, phage display technology has some advantages such as mature research system, low cost, and simpler operation that make it well recognized and praised by the majority of researchers in this field. Here, we reviewed the recent progress of applying phage display technology to explore diverse cyclic peptide libraries, which, we believe, will contribute more valuable candidate cyclic peptide drugs in clinical research.

Evaluation of the effectiveness of PICC catheterization in breast cancer patients by multidisciplinary team / 中国实用护理杂志

Objective:To explore the practical effect of PICC catheterization in breast cancer patients by a multidisciplinary team led by specialist nurses.Methods:Choose Affiliated Tumor Hospital, Xinjiang Medical University in March 2018 to January 2020, 120 cases of breast cancer patients undergoing chemotherapy, according to the random number method, 60 cases were divided into control group and test group, control group given routine nursing care, experimental group on the basis of conventional nursing to the specialist nurses as the leading multidisciplinary team management mode to compare two groups of patients with a success rate of puncture complications patients satisfaction and unscheduled decannulation rate before and after the implementation of the multidisciplinary model nurse satisfaction.Results:The one-time puncture success rate, unplanned extubation rate, incidence of mechanical phlebitis, medical adhesion-related skin injury, puncture point infection, and catheter blockage rate were 98.3% (59/60), 10.0% (6/60), 8.3% (5/60), 1.7% (1/60), 10.0% (6/60), and 10.0% (6/60), respectively. The control group was 88.3% (53/60), 20.0% (12/60), 20.0% (12/60), 13.3% (8/60), 18.3% (11/60) and 21.7% (13/60), respectively. The difference was statistically significant ( χ 2 values were 4.821-14.911, P<0.05). The satisfaction scores of patients in the experimental group were (17.05±1.43), (17.13±1.28) and (4.38±0.56) points respectively in the three dimensions of nurse skill level, nursing service experience and health education guidance, while those in the control group were (14.53±2.10), (15.03±1.38) and (3.10±0.75) points respectively, the difference was statistically significant ( t values were 0.576, 0.623, 0.699, P<0.001). Nurse satisfaction after the implementation of the multidisciplinary model on the professional ability, job security, teamwork, self-assessment score four dimensions, respectively (12.73±1.02), (24.00±3.52), (16.42±2.06), (13.00±1.83) points, not the implementation of the multidisciplinary model its satisfaction each dimension score (9.69±1.49), (7.88±2.07), (11.92±1.32), (8.88±1.18) points, improved from the previous implementation, the difference was statistically significant ( t values were 0.576-0.798, P<0.001). Conclusions:The multidisciplinary team management model led by specialist nurses is applied to the PICC management of breast cancer patients, which not only reduces the incidence of catheter complications, but also improves the quality control level of PICC and the satisfaction of patients and nurses, in order to further promote intravenous treatment. Specialized development provides guidance.

Endoplasmic reticulum stress and NOD-like receptor protein 3 involves in intestinal mucosal injury induced by severe heat stroke / 中华急诊医学杂志

Objective:To observe whether endoplasmic reticulum stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation were involved in severe heat stroke induced intestinal mucosal injury and to investigate the potential protective effect of the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid (4-PBA).Methods:Thirty male BALB/c mice were randomly (random number) assigned to 3 groups: the control group, heat stroke group (HS), and 4-PBA pretreatment group (4-PBA+HS, 4-PBA 120 mg/kg, intraperitoneal injection). Mice in the control group were placed at room temperature, while mice in the HS group and 4-PBA+HS group were placed in a prewarmed chamber [temperature (35.5±0.5) °C, humidity (60.0±5.0)%]. A rectal temperature (Tc) that reached 42 °C was considered to indicate severe heat stroke. The concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) in intestinal homogenate were analyzed by a colorimetric method, serum interleukin-1β (IL-1β) and interleukin-18 (IL-18) were assessed by ELISA, intestinal histopathology was evaluated by hematoxylin and eosin (HE) staining, intestinal ultrastructure was observed by electron microscopy, and the protein expression of GRP78, CHOP, NLRP3 and cleaved caspase-1 were analyzed by Western blot. Data were statistically analyzed by ANOVA test and LSD- t multiple comparison test if homogeneous variance, or analyzed by Welch test and Dunnett's T3 multiple comparison test if heterogeneous variance. Results:The concentration of MDA in the HS group was increased ( t=14.243, P<0.01), while SOD was decreased compared with that in the control group ( t=7.781, P<0.01), and the concentrations of serum IL-1β and IL-18 were significantly elevated ( t=12.664, P<0.01; t=16.240, P<0.01). Under light microscopy, extensive destruction of small intestinal villi and inflammatory cell infiltration were observed in the intestines of mice with severe heat stroke. Transmission electron microscopy showed that endoplasmic reticulum structures were significantly expanded, and mitochondria were vacuolated in the intestines of mice with severe heat stroke. Compared with those in the control group, the protein expression levels of GRP78, CHOP, NLRP3 and cleaved caspase-1 in the small intestine were elevated in the HS group ( t=14.824, P <0.01; t=12.667, P<0.01; t=9.298, P<0.01; and t=6.588, P=0.001). Compared with those in the HS group, mice in the 4-PBA pretreatment group exhibited reduced concentrations of MDA ( t=9.167, P<0.01), increased SOD ( t=6.077, P<0.01) , and reduced serum IL-1β and IL-18 levels ( t=4.889, P= 0.001; t=5.693, P<0.01). In addition, 4-PBA pretreatment significantly alleviated the pathological disruption and ultrastructural damage to small intestine tissues. Moreover, 4-PBA pretreatment reduced GRP78, CHOP , NLRP3 and cleaved caspase-1 protein expression ( t=9.080, P<0.01; t=7.152, P<0.01; t=4.249, P=0.005; t=3.650, P=0.011). Conclusions:Endoplasmic reticulum stress and NLRP3 inflammasome are involved in intestinal mucosal injury induced by severe heat stroke. 4-PBA plays a protective role by alleviating endoplasmic reticulum stress and NLRP3 inflammasome activation.