Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

The most common type of intracranial malignancy is glioma. Although the current treatments are surgery, radiation and chemotherapy, the prognosis for patients with glioma is not promising. Therefore, it becomes critical to find an effective management. The literature shows that microRNA (miRNA) plays an important role in tumorigenesis and progression. Based on this, this study aimed to investigate the molecular mechanism of miR-525-5p in regulating the migration, invasion and proliferation of glioma cells. The TCGA database was used to identify perilipin 3 (PLIN3) differentially expressed in normal tissues and glioma tissues, and the CGGA and GEPIA databases were used to query that high expression of PLIN3 was associated with poor prognosis in glioma patients and Western blot experiments revealed that PLIN3 was highly expressed in glioma cells (P<0. 05) . The results of wound healing assay and Transwell invasion assay showed that knockdown or overexpression of PLIN3 respectively inhibited or promoted the migration and invasion of glioma cells (P < 0. 05) . Dual luciferase assays confirmed that PLIN3 could bind to miR-525-5p target. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) showed that miR-525-5p expression was lower in LN229 and U251 glioma cells than in human astrocyte (HA) (P < 0. 05) . Transwell assay and 5-ethynyl-2-deoxyuridine (EdU) cell proliferation assay verified that down- or up-regulation of miR-525-5p could reverse the effects of overexpression or knockdown of PLIN3 on LN229 glioma cells (P<0. 05) . Taken together, miR-525-5p was able to regulate the migration, invasion and proliferation of glioma cells by targeting PLIN3.

Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.
COVID-19 ; Consensus ; Humans ; Oral Health ; Oral Medicine

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective To investigate the population dynamics and Echinococcus infections in small rodents around human settlement in Yushu City, Qinghai Province. Methods Rodents were captured using the mouse trap method in pastures from Batang Township and Longbao Township of Yushu City, Qinghai Province on May, August and October, 2018. The body weight and snout-vent length of all captured rodents were measured, and the species was identified according to the rodent morphology. Genomic DNA was extracted from rodent liver specimens and lesion specimens, and the mitochondrial cox1 gene of Echinococcus was amplified using PCR assay for identification of parasite species. In addition, the tissue specimens positive for PCR assay were sampled for pathological examinations. The prevalence of Echinococcus infections was estimated in rodents, and a phylogenetic tree was created based on Echinococcus cox1 gene sequences. Results A total of 285 small rodents were captured, including 143 Ochotona curzoniae (50.2%), 141 Lasiopodomys fuscus (49.5%), and 1 Neodon irene (0.3%), and there was a remarkable variation in habitat selection among these three rodent species. The number of L. fuscus correlated positively with vegetation coverage (r = 0.350, P = 0.264), with the greatest number seen in August, and the number of O. curzoniae negatively with vegetation coverage (r = −0.371, P = 0.235), with the highest number seen in August and the lowest number in May. The female/male ratios of O. curzoniae and voles were 1:0.96 and 0.82:1, respectively. The body weight (r = 0.519, P < 0.01) and snout-vent length (r = 0.578, P < 0.01) of O. curzoniae showed a tendency towards a rise with month, while the body weight (r = −0.401, P < 0.01) and snout-vent length (r = −0.570, P < 0.01) of voles presented a tendency towards a reduction with month. No Echinococcus infection was detected in voles, while 2.1% prevalence of E. shiquicus infection was seen in O. curzoniae. Phylogenetic analysis revealed consistent sequences of cox1 gene from E. shiquicus in Yushu City of Qinghai Province and Shiqu County, Ganzi Tibetan Autonomous Prefecture of Sichuan Province. Conclusions The small rodents around the human settlement in Yushu City of Qinghai Province mainly include O. curzoniae and L. fuscus, with the greatest numbers seen in May and August, respectively. Following the concerted efforts for echinococcosis control, the prevalence of Echinococcus infections is low in small rodents around the human settlement in Yushu City; however, there is still a risk of echinococcosis transmission.

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G CONCLUSION PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.
Apoptosis ; Bortezomib/pharmacology* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Multiple Myeloma

Objective:To investigate the technique and efficacy of PTES for treatment of L5/S1 disc herniation.Methods:PTES was performed on 52 cases of L5/S1 herniations without spinal instability and central spinal canal stenosis,including 24 cases of high iliac crest,from November 2012 to April 2013.The operation duration,frequency of intraoperative fluoroscopy,blood loss and hospitalization days were recorded.Leg pain was evaluated by using the visual analog scale(VAS)Preoperatively and immediately,1 week,1 month,2 months,3 months,6 months,1 year and 2 years after surgery.The results were determined to be excellent,good,fair,or poor according to the Macnab classification,and complications were observed at 2-year follow-up.Objective:The mean operation duration was(56.3 ±11.5)min per segment.The median frequency of intraoperatively fluoroscopy was 5(3-14)times.The median blood loss was 5(2-20)mL.The median hospital stay was 3(2-4)days.The average postoperative follow-up was(26.2±2.0)months.The median preoperative VAS score of leg pain was 9(6-10),1(0-3)immediately after the operation and 0(0-3)2 years after operation,and the differences were statistically significant(P<0.001).There were 3 cases of lower limb rebound pain 1 week after operation,which were relieved within 2 months after operation.The rate of excellent and good curative effect was 98.1％(51/52)2 years after operation.No complications such as nerve injury,infection,abdominal organ damage and rupture of large vessels occurred.No recurrence occurred.Conclusions:PTES for L5/S1 disc herniation including the cases with high iliac crest is an easy,effective and safe technique.The method has the advantages of simple positioning,easy puncture,simple steps and less fluoroscopy,and the learning curve is not steep for surgeons.

OBJECTIVES: To investigate the genetic polymorphisms of 21 short tandem repeat （STR） loci （D3S1358, D13S317, D7S820, D16S539, Penta E, D2S441, TPOX, TH01, D2S1338, CSF1PO, Penta D, D10S1248, D19S433, vWA, D21S11, D18S51, D6S1043, D8S1179, D5S818, D12S391 and FGA）. METHODS: A total of 560 blood samples were collected from unrelated healthy individuals of Han population in Hunan Province. Chelex-100 extraction method was applied to the extraction of genomic DNA, and an AGCU EX22 Kit and 9700 STR amplification was used in amplification reactions. The products were separated and analyzed on 310 Genetic Analyzer. RESULTS: A total of 248 alleles were observed, the allelic frequencies ranging from 0.001 to 0.518. Observation of genotype distributions for each locus showed no deviations from Hardy-Weinberg equilibrium except Penta E （P=0.023）. The combined power of discrimination, combined power of exclusion, and combined matching probability of the 21 STR loci were approximately 0.999 999 999 999 999 999 999 999 8, 0.999 999 998, and 1.36×10⁻²⁵, respectively. CONCLUSIONS The 21 STR loci show high polymorphisms in the Han population, which can provide valuable data and a theoretical basis for forensic individual identification and paternity testing.
Alleles ; Asian People/genetics* ; China ; DNA Fingerprinting ; Gene Frequency ; Genetic Testing ; Genetics, Population ; Genotype ; Humans ; Microsatellite Repeats ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Probability

OBJECTIVETo investigate the therapeutic efficacy of nonmyeloablative allogeneic hematopoietic stem cells transplantation for severe acquired aplastic anemia (SAA).

METHODSFourteen patients with severe acquired aplastic anemia received nonmyeloablative allogeneic hematopoietic stem cells transplantation from HLA matched sibling donors, among them 8 cases were dagnosed as SAA-I, 6 cases were diagnosed as SAA-II. The conditioning regimen consisted of fludarabine (FIUD), cyclophosphamide (CTX) and anti-thymocyte globulin (ATG/ALG). The prophylaxis for graft-versus-host disease (GVHD) was performed with cyclosporine (CsA) combined with mycophenolate mofetil (MMF) or tacrolimus (FK506).

RESULTSAll the patients gained a quick successfully engraftment of donor hametopoietic cells. The mean recovery time for neutrophil and platelet was 9 d and 13 d respectively. All the patients have acquired a full donor chimerism before 14 d. There were only 2 cases of GVHD: one out of them was acute skin GVHD (grade I) at day 70 after transplantation and the other was chronic liver GVHD (grade I) in 1 years after transplantation, the GVHD more than degree II did not coccur in all patients, 9 patients with bacterial and fungal mixed infection and (or) virus infection were observed, and improved after anti-infection therapy. The median follow-up time were 54.5 months (ranged between 5-144 months), and 12 patients remain disease-free survival currently, only 2 patients died of fungal infectin.

CONCLUSIONTransplantation of nonmyeloablative allogeneic hematopoietic stem cell is safe and effective for the treatment of severe acquired aplastic, but the prevention, treatment and monitoring of infection need to be enhance.

Allografts ; Anemia, Aplastic ; Antilymphocyte Serum ; Cyclophosphamide ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mycophenolic Acid ; analogs & derivatives ; Neutrophils ; Siblings ; Tissue Donors ; Transplantation Conditioning ; Vidarabine ; analogs & derivatives