Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

Objective:To investigate the application effect of discharge preparation service based on theory of goal attainment on patients with cervical spinal cord injury.Methods:A retrospective cohort study was conducted to analyze the clinic data of 60 patients with cervical spinal cord injury admitted to Zhengzhou Orthopedics Hospital from January 2017 to December 2022, including 49 males and 11 females, aged 23-79 years [(52.2±13.5)years]. Patients were all treated with cervical decompression fusion and internal fixation. Patients admitted from January 2017 to December 2019 were treated with conventional nursing intervention (conventional nursing group, n=30) and patients admitted from January 2020 to December 2022 were treated with discharge preparation service based on theory of goal attainment (discharge preparation service group, n=30). The readiness for hospital discharge of the two groups was compared using the Chinese version of Readiness for Hospital Discharge Scale (RHDS) at 4 hours before discharge. The degree of cervical spinal cord dysfunction of the two groups were compared using Japanese Orthopedic Association (JOA) score before intervention, at discharge and at 6 months after discharge. The complication and unplanned readmission rates of the two groups were compared at 6 months after discharge. Results:All the patients were followed up for 6 months. At 4 hours before discharge, the scores of the three parameters of RHDS containing personal status, adaptability and anticipatory support and the total score of the discharge preparation service group were (20.9±3.5)points, (35.9±2.2)points, (30.4±3.0)points and (87.1±7.8)points respectively, higher than those of the conventional nursing group [(16.2±1.7)points, (32.5±2.2)points, (26.3±2.1)points and (75.0±5.6)points respectively] ( P<0.01). There was no statistically significant difference in the JOA score of the two groups before intervention ( P>0.05). The JOA scores of the discharge preparation service group at discharge and at 6 months after discharge were (11.8±1.7)points and (13.8±1.5)points respectively, higher than those of the conventional nursing group [(10.3±1.8)points and (11.6±1.9)points respectively] ( P<0.01). At 6 months after discharge, the complication rate of the discharge preparation service group was 6.7% (2/30), lower than that of the conventional nursing group [36.7% (11/30)] ( P<0.05). The unplanned readmission rate of the discharge preparation service group was 3.3% (1/30), lower than that of the conventional nursing group [23.3% (7/30)] ( P<0.05). Conclusion:For patients with cervical spinal cord injury, discharge preparation service based on theory of goal attainment can improve the discharge readiness, promote spinal functional recovery and reduce the complication and unplanned readmission rates.

Objective To analyze the expression level of YEATS2 in hepatocellular carcinoma(HCC)about its clinical prognosis and therapeutic value based on biological information from the cancer genome atlas(TCGA)and human protein atlas(HPA)databases.Methods The mRNA expression data and clinical information of HCC were downloaded from the TCGA database,the expression of YEATS2 between HCC tissues and normal tissues was analyzed by using the R software,and the protein expression differences were preliminary verified by the HPA database.The expression differences of YEATS2 between various clinical features of HCC were compared,and their effects on the survival of HCC patients by Kaplan-Meier method and COX regression analysis were then evaluated.Receiver operating characteristic(ROC)curves were plotted to evaluate their diagnostic values.The biological functions of YEATS2 in HCC were analyzed using gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis.The relationship between YEATS2 expression and tumor microenvironment(TME)was analyzed by the"ESTIMATE"algorithm,and its relationship with tumor-infiltrating immune cells(TIICs)was assessed by CIBERSORT.Analysis of YEATS2 expression levels to immune checkpoints and drug sensitivity was performed using the R package.Results The expression of YEATS2 was increased in HCC tissues(P=4.96e-21),and its expression level was correlated with age,clinical stage,pathological grade and T stage(all P＜0.05).Overall survival(OS)(P＜0.001)and progression-free survival(FPS)(P=0.016)were decreased in HCC patients with high expression of YEATS2,COX regression results showed that the expression level ofYEATS2 was associated with poor prognosis in HCC patients(OS:HR=2.167,95％CI:1.441～3.261,P=2.06e-04),and it was an independent risk factor for predicting poor prognosis in HCC patients(OS:HR=1.891,95％CI:1.243～2.877,P=0.003).The ROC curve suggested the AUCs for 1,3 and 5 years were 0.677,0.622 and 0.612,respectively,indicating good predictive ability.The TCGA database screened a total of 6 764 differential genes in the YEATS2 high and low expression groups,of which 4 094 genes were up-regulated and 2 670 genes were down-regulated in the YEATS2 high expression group.The results of GO and KEGG enrichment analyses showed that the differentially differentiated genes in the YEATS2 high expression group were mainly enriched in immunoregulation,and cell cycle regulation drug resistance pathway.The results of the TME score showed that the YEATS2 high expression group caused a decrease in immunity score(P＜0.01).The correlation between YEATS2 and TIICs showed that YEATS2 expression was positively correlated with the level of M0-type macrophage infiltration levels(r=0.48,P＜0.001)and 23 immune checkpoint genes(r=0.20～0.46,all P＜0.05),and was negatively correlated with the CD8+T-cells,plasma cells and monocyte(r=-0.26,-0.29,-0.30,P=0.021,0.011,0.008).Drug sensitivity analysis showed that the half maximal inhibitory concentration(IC50)of cabozantinib,lincitinib,doxorubicin,and cyclobenzaprine in patients with high expression of YEATS2 was higher than those in patients with low expression(all P＜0.01).Conclusion YEATS2 was highly expressed in HCC,and the expression level was associated with poor prognosis in HCC patients.YEATS2 can be used as a biomarker for the clinical early diagnosis,prognosis and immunotherapy of HCC,which may provide new ideas for clinical diagnosis and treatment.

In the progression of end-stage liver disease,the incidence of sleep disorders in patients with liver cirrhosis is high.Currently,western medicine treatment has obvious liver and kidney damage and adverse reactions after discontinuation,which affects the therapeutic effect.Cirrhosis and sleep disorders can be separately attributed to the category of"abdominal mass"and"insomnia"in traditional Chinese medicine.The"abdominal mass"is caused by the disorder of liver and spleen qi movement,as well as the obstruction of phlegm-dampness and blood stasis.In the development of"abdominal mass",the liver failed in ensuring free movement of qi,the spleen failed in transportation and transformation,liver yin and liver blood became insufficiency and the imbalance of yin and yang in the zang-fu organs became imbalanced,and then the ethereal soul depart from the housing,which leads to"insomnia"as an outward manifestation.Professor ZHOU Xiao-Zhou focuses on the concept of qi and blood,and points out that the pathogenesis of sleep disorder in cirrhosis is characterized by liver stagnation and spleen deficiency.He proposed that the treatment principle is to regulate the liver and spleen simultaneously,as well as to nourish the heart and calm the mind.Professor ZHOU has developed Ganyinghua Anshen Formula for treating sleep disorders in cirrhosis,which is derived from the modification of Xiangsha Liujunzi Decoction,and is composed of 14 Chinese medicines of vinegar-prepared Cyperi Rhizoma,Amomi Fructus,Coicis Semen,Dioscoreae Rhizoma,bran-fried Atractylodis Macrocephalae Rhizoma,Galli Gigerii Endothelium Corneum,Gardeniae Fructus,Codonopsis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Citri Reticulatae Pericarpium,Sclerotium Poriae Pararadicis,Longan Arillus,Albiziae Cortex,and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The formula has achieved remarkable clinical effect.The clinical experience of Professor ZHOU Xiao-Zhou for treating sleep disorders in cirrhosis through regulating the liver and spleen simultaneously will provide a reference for its clinical treatment with traditional Chinese medicine.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

The advantages of fluorescence detection of uric acid were introduced compared to the traditional detection methods.The preparation process,detection principle and performance of organic,inorganic and organic-inorganic hybrid fluorescent probes were reviewed.The advantages and disadvantages of kinds of fluorescent probes were analyzed when used for uric acid detection,and the futural directions were pointed out for related research.[Chinese Medical Equipment Journal,2024,45(6):93-104]

Objective:To compare the effects of unilateral thoracic paravertebal block with lidocaine on hemodynamic and the level of consciousness during double lumen endotracheal intubation.Methods:From June to october 2021,a total of 40 patients American Society of Anesthesiologists(ASA)physical status Ⅰ-Ⅱ,aged 19-65 years,scheduled for elective thoracic sugeries in Peking University Interna-tional Hospital block with under general anesthesia requiring orotracheal intubation were recruited and di-vided into two groups:The double-lumen endobronchial intubation(group C)and double-lumen endo-bronchial intubation after thoracic paravertebal block with lidocaine(group P).After an intravenous an-esthetic induction,the orotracheal double-lumen intubation was performed using a Macintosh direct laryn-goscopy,respectively.Invasive blood pressure(BP)and heart rate(HR)were recorded before and after anesthetic induction,immediately after intubation and 5 min after intubation with 1-minute interval and the intubation time was also noted.Rate-pressure product(RPP)were calculated.Results:After anes-thetic induction,BP and RPP in the two groups decreased significantly compared with their preinduction values.As comparison with their postinduction values,the orotracheal intubation in the two groups caused significant increases in BP,HR and RPP.Diastolic blood pressure(DBP)and mean arterial pressure(MAP)increased significantly and lasted for 1-minute in group C compared with the baseline values.Systolic blood pressure(SBP)was not significant change and DBP increased significantly immediately af-ter intubation in group P.HR of both groups after intubation were significantly higher than their baseline values and lasted for 4 min in group C,HR increased significantly immediately after intubation in group P.SBP,DBP,MAP,HR and RPP after intubation in group P were significantly lower than those of group C during the observation period.The value of BIS was similar between the two groups.Compared with group C,the incidence of SBP greater than 30％and RPP greater than 22 000 was significantly lower in group P in the observation period,and no patient in group P developed RPP greater than 22 000.At the end of the incidence of SBP less than 30％of the basal value and HR less than 30％of the baseline,no severe bradycardia occurred in both groups.Conclusion:During double-lumen endobronchial intubation,unilateral thoracic paravertebal block with lidocaine can provide less hemodynamic response and level of conscionsness.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.