Palbociclib tablet is an improved product obtained by optimizing the prescription process of palbociclib capsule,which can reduce the impact of antacids on piperacillin exposure.Unlike the postprandial medication requirements for the capsule formulation,tablets can be administered without considering food intake.Due to its unique biopharmaceutical properties,the research requirements for human bioequivalence(BE)study of palbociclib tablets are different from those of regular generic drugs.This article analyzes the drug characteristics of palbociclib,as well as the biopharmaceutical characteristics of the capsule and the tablet,and proposes research recommendations for the bioequivalence of generic palbociclib tablets in human,providing reference for the generic research of palbociclib tablets in China.

Endo-beta-N-acetylglucosaminidase (ENGase) is widely distributed in various organisms. The first reported ENGase activity was detected in Diplococcus pneumoniae in 1971. The protein (Endo D) was purified and its peptide sequence was determined in 1974. Three ENGases (Endo F1-F3) were discovered in Flavobacterium meningosepticum from 1982 to 1993. After that, the activity was detected from different species of bacteria, yeast, fungal, plant, mice, human, etc. Multiple ENGases were detected in some species, such as Arabidopsis thaliana and Trichoderma atroviride. The first preliminary crystallographic analysis of ENGase was conducted in 1994. But to date, only a few ENGases structures have been obtained, and the structure of human ENGase is still missing. The currently identified ENGases were distributed in the GH18 or GH85 families in Carbohydrate-Active enZyme (CAZy) database. GH18 ENGase only has hydrolytic activity, but GH85 ENGase has both hydrolytic and transglycosylation activity. Although ENGases of the two families have similar (β/α)8-TIM barrel structures, the active sites are slightly different. ENGase is an effective tool for glycan detection andglycan editing. Biochemically, ENGase can specifically hydrolyze β‑1,4 glycosidic bond between the twoN-acetylglucosamines (GlcNAc) on core pentasaccharide presented on glycopeptides and/or glycoproteins. Different ENGases may have different substrate specificity. The hydrolysis products are oligosaccharide chains and a GlcNAc or glycopeptides or glycoproteins with a GlcNAc. Conditionally, it can use the two products to produce a new glycopeptides or glycoprotein. Although ENGase is a common presentation in cell, its biological function remains unclear. Accumulated evidences demonstrated that ENGase is a none essential gene for living and a key regulator for differentiation. No ENGase gene was detected in the genomes of Saccharomyces cerevisiae and three other yeast species. Its expression was extremely low in lung. As glycoproteins are not produced by prokaryotic cells, a role for nutrition and/or microbial-host interaction was predicted for bacterium produced enzymes. In the embryonic lethality phenotype of the Ngly1-deficient mice can be partially rescued by Engase knockout, suggesting down regulation of Engase might be a solution for stress induced adaptation. Potential impacts of ENGase regulation on health and disease were presented. Rabeprazole, a drug used for stomach pain as a proton inhibitor, was identified as an inhibitor for ENGase. ENGases have been applied in vitro to produce antibodies with a designated glycan. The two step reactions were achieved by a pair of ENGase dominated for hydrolysis of substrate glycoprotein and synthesis of new glycoprotein with a free glycan of designed structure, respectively. In addition, ENGase was also been used in cell surface glycan editing. New application scenarios and new detection methods for glycobiological engineering are quickly opened up by the two functions of ENGase, especially in antibody remodeling and antibody drug conjugates. The discovery, distribution, structure property, enzymatic characteristics and recent researches in topical model organisms of ENGase were reviewed in this paper. Possible biological functions and mechanisms of ENGase, including differentiation, digestion of glycoproteins for nutrition and stress responding were hypothesised. In addition, the role of ENGase in glycan editing and synthetic biology was discussed. We hope this paper may provide insights for ENGase research and lay a solid foundation for applied and translational glycomics.

Objective To assess the nutritional status and dietary quality of medical students and its influencing factors.Methods Students from Shanghai Medicial College of Fudan University were recruited to complete the 7-day and 24-hour dietary records,with food consumption measured by weight.A comprehensive evaluation of the students'dietary quality was carried out by comparing their actual nutrient intake against recommended levels and calculating the component score of the Chinese Healthy Eating Index(CHEI).Factor analysis was used to extract dietary patterns.All subjects were further divided into high score group and low score group based on total CHEI.Binary Logistic regression was used to determine the factors influencing dietary quality.Results The study participants had an average daily energy intake of(2 057.02±501.87)kcal/d,80%from on-campus canteen meals.Carbohydrates,proteins and fats contributed to 48.90%,16.55%and 36.07%of the total energy intake,respectively.The CHEI median score was 67.55.Component scores for tubers,vegetables,fruits,dairy,fish and seafood,and nuts were below 60%,indicating an unbalanced diet.Being in the graduate stage(OR=0.53,95%CI:0.28-0.98)and having unreasonable body weight expectations(OR=0.37,95%CI:0.17-0.81)were associated with lower CHEI scores.Conversely,higher CHEI scores were associated with the fruit-dairy dietary pattern(OR=8.20,95%CI:3.39-19.84),the tuber-vegetable dietary pattern(OR=3.41,95%CI:1.58-7.32),and lower rates of on-campus dining(OR=1.92,95%CI:1.02-3.59).Conclusion The energy intake of students at Shanghai Medical College of Fudan University appears to be adequate.However,a relatively high proportion of energy supply from fat intake indicates a need for improvement in their dietary structure.The dietary quality of students is mainly influenced by their educational level,weight expectations and dietary patterns.

convalescents, and to screen for broad-spectrum neutralizing antibodies against the SARS-CoV-2 RBD. Methods Using biotinylated RBD as a molecular probe, flow cytometry was employed to perform single-cell sorting of B cells from peripheral blood mononuclear cells (PBMCs) of convalescents. The obtained B cells were lysed and subjected to reverse transcription, followed by nested PCR amplification of the heavy and light chains of antibodies was conducted using random primers. The amplified products were cloned into corresponding expression vectors, and the respective matched heavy-light chain plasmids were co-transfected into 293F cells for expression. Monoclonal antibodies were then purified using Protein A column chromatography. Neutralization experiments were conducted with the wild-type (WT) pseudovirus, and antibodies with IC50<0.1 μg/mL were selected for further testing of neutralizing breadth and potency against the wild-type (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and currently prevalent pseudovirus strains (XBB, BA.5, BF.7). Results A total of 21 RBD-specific monoclonal B cells were obtained from two recovered patients, resulting in the isolation of 13 pairs of antibody light/heavy chains. Nine antibodies were successfully expressed, with P1-A1, P1-B6, and P1-B9 exhibiting IC50 values below 0.1 μg/mL against the pseudovirus of the wild-type strain (WT). Specifically, P1-B6 effectively neutralized the wild-type strain (WT), Beta variant (B.1.351), and Delta variant (B.1.617.2), with IC50 values reaching 0.01 μg/mL. P1-B9 demonstrated effective neutralization against the wild-type strain (WT), Beta variant (B.1.351), Delta variant (B.1.617.2), and Gamma variant (P.1) pseudoviruses, with IC50 values of 0.42 μg/mL, 0.63 μg/mL, 0.28 μg/mL, and 2.50 μg/mL, respectively. Additionally, P1-B6 exhibited good neutralization against BA.5 and BF.7 pseudoviruses, with IC50 values of 0.06 μg/mL and 0.09 μg/mL, respectively. Conclusions Infection with the SARS-CoV-2 WT strain can induce the generation of neutralizing antibodies with broad-spectrum activity. Generating these broadly neutralizing antibodies does not require an excessively high somatic hypermutation. The obtained antibodies can be used as candidates for SARS-CoV-2 diagnosis and prevention.

Objective:To establish and validate the prediction model for bone marrow metastasis (BMM) in malignant tumors by screening out laboratory multiparameters.Methods:This case-control study collected 444 cases of malignant tumor patients who were hospitalized in the First Hospital of Jilin University from March 2018 to March 2024, including 243 cases for model establishment set and 201 cases for model validation set. The model establishment set was divided into BMM positive group (81 cases) and BMM negative group (162 cases), and the model validation set was divided into positive group (67 cases) and a negative group (134 cases). We collected patients′ clinical information such as gender, age, clinical diagnosis, and results of 47 laboratory tests including routine blood analysis, coagulation, liver function, tumor markers, potassium, sodium, chloride, and calcium ion tests, bone marrow morphology, and bone marrow biopsy. BMM was taken as the outcome event, differencial variables were analyzed using inter group comparisons, the correlation among parameters was analyzed using Pearson correlation analysis, the risk factors for BMM were analyzed using multivariate conditional logistic regression analysis, to establish logistic model, followed by efficiency evaluation on BMM predictive model using receiver operating characteristic (ROC) curves.Results:In the model establishment set, Pearson correlation analysis of 28 parameters that differed between the BMM positive and negative groups revealed that the correlation coefficients of 17 parameters, including mean platelet volume (MPV), hematocrit (HCT), hemoglobin (HGB), and prothrombin time (PT), were no more than 0.6 ( P<0.05). Further multivariate conditional logistic regression analysis demonstrated that MPV, HGB, HCT, PT, red cell distribution width (RDW), platelet count (PLT), alkaline phosphatase (ALP), chloride (Cl -), and mean erythrocyte hemoglobin concentration (MCHC) were the risk factors of BMM occurence in malignancy [MPV ( OR=9.929, 95% CI 2.688-71.335), HCT ( OR=8.232, 95% CI 6.223-9.841), HGB ( OR=4.300, 95% CI 1.947-16.577), PT ( OR=3.738, 95% CI 1.359-11.666), RDW ( OR=1.995, 95% CI 1.275-3.807), ALP ( OR=1.025, 95% CI 1.012-1.045), PLT ( OR=1.014, 95% CI 1.002-1.031), MCHC ( OR=0.724, 95% CI 0.523-0.880) and Cl -( OR=0.703, 95% CI 0.472-0.967)]. In the model establishment set, combiation of risk factors provided an AUC of 0.943 (95% CI 0.898-0.987, P<0.001), a sensitivity of 86.3%, and a specificity of 89.2% for BMM prediction. In the model validation set, the AUC was 0.924 (95% CI 0.854-0.960, P<0.001), with a sensitivity and specificity of 86.7% and 83.8%, respectively. Conclusion:This study built and validated a multiple-parameter model for BMM, which may facilitate the timely detection of BMM and provide reference for decision making of bone marrow aspiration.

Objective To evaluate the rabbit modle of frozen shoulder induced by persistent strain injuries and ice com-pression.Methods Twelve clean,healthy male New Zealand rabbits with a mass of(2 500±500)g were selected and randomly divided into a blank group and a control group with 6 rabbits in each group.In the control group,the rabbits were modeled with persistent strain injuries and ice compression,the general conditions of the rabbits and the active and passive activities of the shoulder joint were observed and their body weights were recorded.MRI was performed on the affected shoulder joints at 6 d and 29 d after modelling to observe the fluid and soft tissue;HE staining was used to observe the morphology of the rabbit bi-ceps longus tendon and the synovial membrane of the joint capsule;Masson staining was used to observe the fibrous deposits of the rabbit biceps longus tendon and the synovial membrane of the joint capsule,and the fibrous deposits were analysed semi-quantitatively by Image J software.Results Six days after the end of modeling,the active movement of the shoulder joints in the control group was limited,the passive movement was not significantly limited,and they walked with a limp;29 days after the end of the modeling,the active and passive movements of the shoulder joints in the model group were severely limited.Com-pared with the blank group(2.50±0.14)kg,the body weight of the model group(2.20±0.17)kg was significantly reduced(P＜0.01).MRI showed that 6 days after modelling,the muscles around the shoulder joint were not smooth in shape,the joint cap-sule structure was narrowed and a large amount of fluid was seen in the joint cavity;29 days after modelling,the muscles around the shoulder joint were rough in shape,structure of the joint capsule was unclear and the fluid in the joint cavity was reduced compared with 6 days after modelling.Pathological staining showed that the long-headed biceps tendon fibres in the control group were disorganised,curled or even broken,and the synovial tissue of the joint capsule was heavily vascularised,with col-lagen fibre deposits and severe inflammatory cell infiltration.The fiber deposition of the long head of biceps brachii in the mod-el group[(23.58±3.41)％,(27.56±3.70)％]and synovial tissue[(41.78±5.59)％,(62.19±7.54)％]were significantly higher than those in the blank group[(1.79±1.03)％,(1.29±0.63)％]at 7 and 30 days after modeling and synovial tissue fiber de-position[(8.15±3.61)％,(11.29±7.10)％],as shown by the semi-quantitative analysis of Masson staining results by Image J software.And the longer the time,the more severe the fibrosis(P＜0.01).Conclusion The behavioral,imaging and pathological findings showed that the rabbit frozen shoulder model with persistent strain injuries and ice compression is consistent with the clinical manifestations and pathogenesis of periarthritis,making it an ideal method for periarthritis research.

Objective To apply a COMSOL-based finite element analysis method to investigating the electric field effects produced by the human lower limb musculoskeletal system under the synergistic effects of stress field and electromagnetic field.Methods Firstly,a 3D human body model was constructed by Maxon Cinema 4D R21 software,and then imported into COMSOL 6.1 software in STL format.Secondly,an electromagnetic field intervention and stress loading model for the left lower limb of the human body was designed and constructed,in which 15 Hz quasi-pulse group current signals were used for electromagnetic field excitation and the stress field was realized by applying a vibration load with an average compressive force of about 90 N/cm2 to the left foot of the human body.Finally,the electromagnetic properties of human tissue were simulated by numerical simulation,and then the effects of stress field or elecromagnetic field or combined stress field and electromagnetic field on human bioelectric field were compared.Results Simulation results showed that the electric field intensity peaked at the leg joints under both electromagnetic and stress fields acting alone or synergistically,the bioelectric field intensity generated by the human body was related to the distance from the exogenous excitation loading location,and the electric field generated under synergistic action was equivalent to the linear superposition of the bioelectric field in the tissue induced by the electromagnetic field and the stress field acting alone.Conclusion Data supplement is provided for predicting bioelectric field changes within the musculoskeletal tissue,and theoretical foundation is laid for the development and application of multi-physics field synergistic intervention therapy for treating the disorders of the lower limb musculos-keletal system.[Chinese Medical Equipment Journal,2024,45(9):21-26]

Objective:To study the reversal effect of NVP-BEZ235 on doxorubicin resistance in Burkitt lymphoma RAJI cell line.Methods:The doxorubicin-resistant cell line was induced by treating RAJI cells with a concentration gradient of doxorubicin.The levels of Pgp,p-AKT,and p-mTOR in cells were detected by Western blot.Cell viability was detected by MTT assay.IC50 was computed by SPSS.Results:The doxorubicin-resistant Burkitt lymphoma cell line,RAJI/DOX,was established successfully.The expression of Pgp and the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line were both higher than those in RAJI cell line.NVP-BEZ235 downregulated the phosphorylation levels of AKT and mTOR in RAJI/DOX cell line.NVP-BEZ235 inhibited the proliferation of RAJI/DOX cell line,and the effect was obvious when it was cooperated with doxorubicin.Conclusion:The constitutive activation of PI3K/AKT/mTOR pathway of RAJI/DOX cell line was more serious than RAJI cell line.NVP-BEZ235 reversed doxorubicin resistance of RAJI/DOX cell line by inhibiting the PI3K/AKT/mTOR signal pathway.

The canonical transient receptor potential channel(TRPC)proteins form Ca2+-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1-/-mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/-mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1-/-cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factor-kappa B(NF-κB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca2+influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

Objective: To understand the basic characteristics of previously reported patients with hepatitis C and analyze the related factors affecting their antiviral treatment. Methods: A convenient sampling method was adopted. Patients who had been previously diagnosed with hepatitis C in the Wenshan Prefecture of Yunnan Province and Xuzhou City of Jiangsu Province were contacted by telephone for an interview study. The Andersen health service utilization behavior model and related literature were used to design the research framework for antiviral treatment in previously reported hepatitis C patients. A step-by-step multivariate regression analysis was used in previously reported hepatitis C patients treated with antiviral therapy. Results: A total of 483 hepatitis C patients, aged 51.73 ± 12.06 years, were investigated. The proportion of male, agricultural occupants who were registered permanent residents, farmers and migrant workers was 65.24%, 67.49%, and 58.18%, respectively. Han ethnicity (70.81%), married (77.02%), and junior high school and below educational level (82.61%) were the main ones. Multivariate logistic regression analysis results showed that married patients with hepatitis C (OR = 3.19, 95% CI: 1.93-5.25, compared with unmarried, divorced, and widowed patients) with high school education or above (OR = 2.54, 95% CI: 1.54-4.20, compared with patients with junior high school education or below) were more likely to receive antiviral treatment in the predisposition module. Patients with severe self-perceived hepatitis C in the need factor module (compared with patients with mild self-perceived disease, OR = 3.36, 95% CI: 2.09-5.40) were more likely to receive treatment. In the competency module, the family's per capita monthly income was more than 1,000 yuan (compared with patients with per capita monthly income below 1,000 yuan, OR = 1.59, 95% CI: 1.02-2.47), and the patients had a high level of awareness of hepatitis C knowledge (compared with patients with a low level of knowledge, OR = 1.54, 95% CI: 1.01-2.35), and the family members who knew the patient's infection status (compared with patients with an unknown infection status, OR = 4.59, 95% CI: 2.24-9.39) were more likely to receive antiviral treatment. Conclusion: Different income, educational, and marital statuses are related to antiviral treatment behavior in hepatitis C patients. Family support of hepatitis C patients receiving hepatitis C-related knowledge and their families knowing the infection status is more important in promoting the antiviral treatment of patients, suggesting that in the future, we should further strengthen the hepatitis C knowledge of hepatitis C patients, especially the family support of hepatitis C patients' families in treatment.
Humans ; Male ; Antiviral Agents/therapeutic use* ; China ; Hepatitis C/drug therapy* ; Hepacivirus ; Logistic Models