Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Objective To investigate the difference of depressive symptoms between adolescents and adults,and to provide possible basis for early detection of adolescent depression.Methods From July 2021 to June 2022,a total of 4 096 patients with"depression"in the psychiatric clinic of the First Affiliated Hospital of Chongqing Medical University were selected as the research objects.They were divided into the adolescent group(n=2 439)and adult group(n=1 657)according to their ages,and the results of self-rating depression scale(SDS)and symptom checklist 90(SCL-90)were collected and analyzed.Results There were significant differences in nationality,residence,native place,family history and degree of depression between the two groups(P<0.05).The adolescent group has more severe depressive symptoms,which were mainly manifes-ted in negative ideas,obsessive-compulsive symptoms,hostile and interpersonal relationship,and psychotic symptoms(P<0.05).The adult group showed more obvious in sleep(P<0.05).Conclusion Early inter-vention should be carried out for adolescents'depressive symptoms such as negative thoughts.

Objective:To analyze the key points and shortcomings of Traditional Chinese Medicine(TCM)science and technology innovation policy in China,and to provide reference for the subsequent policy optimization.Methods:Searching for TCM science and technology innovation policy texts released at the national level since 2007,and use the two-dimensional analysis framework for quantitative analysis.Results:Among 27 policies,In the X dimension,supply-based,environmental and demand-based policy tools respectively accounted for 48.98%,39.29%and 11.73%.In the Y dimension,the proportion of scientific and technological innovation and achievement transformation was the highest(29.03%);Promoting the development of integrated Chinese and Western medicine was the least used(1.08%).Conclusion:There is a structural imbalance in the application of policy tools,the distribution difference of policy objectives is significant,and the internal policy tools'usage is imbalanced regarding policy objectives.Suggestions:Optimize the internal structure of policy tools.Meanwhile,enhance the structure of policy objectives,and facilitate the dynamic integration and application of policy tools to achieve the policy objectives of scientific and technological innovation in TCM.

Purpose To explore the predictive value of nomogram model for invasive breast cancer with axillary lymph node metastasis.Materials and Methods Retrospective analysis was made on 122 patients suspected to be breast cancer in the General Hospital of Ningxia Medical University from September 2020 to March 2022.According to whether there was axillary lymph node metastasis,all subjects were divided into 57 patients in the metastasis group and 65 patients in the non-metastasis group.All lesions were pathologically confirmed by surgery.The two groups received synthesis of magnetic resonance imaging(syMRI),dynamic contrast enhancement magnetic resonance imaging(DCE-MRI)and diffusion weighted imaging(DWI)scans.The syMRI parameters[including T1,T2,proton density(PD)],DCE-MRI time signal intensity curve,apparent diffusion coefficient(ADC)value of breast lesions were measured.Compared the difference of parameters between the two groups,and screened the independent risk factors of invasive breast cancer with axillary lymph node metastasis.Results Logistic regression results showed that Ki-67(OR=2.971,95%CI 1.306-6.762,P=0.009),lesion size(OR=1.652,95%CI 1.067-2.556,P=0.024),ADCratio(OR=1.685,95%CI 1.014-2.801,P=0.044),T2ratio(OR=3.015,95%CI 1.433-6.340,P=0.003),PDratio(OR=2.782,95%CI 1.471-5.262,P=0.002)were independent risk factors for invasive breast cancer with axillary lymph node metastasis.The comparison of the five models showed that the Logistic regression model had the best performance,with the area under curve of 0.729(95%CI 0.621-0.789),the accuracy,specificity and sensitivity were 70.65%,62.79%and 77.55%,respectively.The accuracy of the nomogram model was tested,and C-index=0.844,the accuracy of the nomogram model established was good,cut-off risk was 0.468,and the cut-off score was 143.50,which means that when the total score exceeds 143.50,the risk of axillary lymph node metastasis would be higher than 46.8%.Conclusion Nomogram model has a good predictive ability for invasive breast cancer patients with axillary lymph node metastasis.

Objective:To investigate the correlations of urinary adverse reactions with dose to the bladder and urethra during external pelvic irradiation for locally advanced cervical cancer.Methods:This study retrospectively collected relevant dosimetric parameters and urinary symptoms, such as frequent, urgent, and painful urination, from locally advanced cervical cancer patients treated with external pelvic irradiation in the Department of Oncology, Affiliated Hospital of Guizhou Medical University. The dosimetric parameters examined in this study included the maximum, minimum, and mean doses to bladder and urethra (i.e., Dmax, Dmin and Dmean), mean doses received in an area of 0.1, 1, and 2 cm 3 around the planning target volume, D0.1 cm 3, D1 cm 3, D2 cm 3, and percentages of irradiated volumes in the whole organ volume under doses of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 Gy, V5 Gy, V10 Gy, V15 Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy, V50 Gy. Then the correlations between urinary symptoms and these dosimetric parameters were analyzed using the independent-sample t-test and the Logistic regression model. Results:The median volumes of bladder and urethra were 294.8 and 4.71 cm 3, respectively. Patients were divided into two groups based on the median division. The univariate analysis showed that urethral Dmax, Dmin, Dmean, V5 Gy, V10 Gy, V15Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy and V50 Gy correlated with urinary complications ( t = 14.30, 21.65, 32.19, 33.36, 16.62, 17.91, 21.52, 20.11, 12.27, 37.25, 30.18, 36.24 and 21.98, P<0.05). The multivariate analysis further indicates that urethral D2 cm 3, V20 Gy, V40 Gy and Bladder V40 Gy, D1 cm 3, D2 cm 3 were independent predictors of grade 2 urinary adverse reactions ( P<0.05). Conclusions:This study reported the correlations of relevant dosimetric parameters of urethra with urinary toxicity during external pelvic irradiation. It holds that urethral D2 cm 3, V20 Gy and V40 Gy should be restricted to minimize the risks of grade 2 urinary complications.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

Using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.

ObjectiveTo understand the utilization of preconception healthcare services and the influencing factors among the women expecting additional childbirth in Jiading District， Shanghai， and to provide references for promoting the utilization of preconception healthcare services under the new population policy. MethodsA questionnaire survey on the utilization of preconception healthcare services and related influencing factors was carried out among 682 women expecting additional childbirth across six subdistricts in Jiading District， Shanghai. The results were statistically analyzed. ResultsThe average age of the women was （31.7±4.5） years， 30.2% of whom were ≥35 years old. The proportion of women having their third or subsequent children was low， at 16.4%. A significant majority， 92.4%， were found to have various risk factors during initial pregnancy screening. The utilization rate of preconception healthcare services among women seeking additional childbirth was relatively low at 26.7%. Awareness of the free preconception check-up program in Jiading District was also low at 28.6%， and the utilization rate for these services was even lower at 7.69%. Unplanned pregnancies were the primary reason for not utilizing preconception healthcare services， accounting for 63.6%. The results of multifactorial binary logistic regression analysis showed that the utilization rate of preconception healthcare services before the current pregnancy was higher for women aged between 35 and 39 compared to women aged ≤29 years old （OR=1.789， 95%CI： 1.033‒3.099）. Women with planned pregnancies had a higher utilization of preconception healthcare services prior to this pregnancy （OR=4.164， 95%CI： 2.627‒6.602）. Women who had received preconception care prior to their first birth had a higher utilization rate of preconception care prior to the current pregnancy （OR=7.534， 95%CI： 4.954‒11.456）. Women without a family history of chronic diseases had a higher utilization rate of preconception healthcare services （OR=1.903， 95%CI： 1.083‒3.345）. ConclusionUnder the context of three-child policy， the proportion of women seeking three or more children in Jiading District is low. Most of these women have risk factors identified during initial pregnancy screenings. The utilization rate of preconception healthcare services and the awareness of the free preconception screening program in Jiading District are both low. Unplanned pregnancies remain the primary reason for failing to receive timely preconception healthcare services. Age， whether the pregnancy was planned， whether the women had received preconception healthcare services before their first baby and family history of chronic diseases are the main factors affecting the utilization of preconception healthcare services. Relevant departments should enhance the promotion of preconception healthcare service programs， especially for women of childbearing age who have not yet given birth， so as to improve the utilization rate of preconception health care services.

Ubiquitin-specific protease 1 (USP1) is one of the deubiquitinating enzymes which has received increasing attention in cancer research. USP1 is overexpressed in many types of cancer cells, and has been found to control tumorigenesis and progression by regulating various proteins associated with tumors, such as SIK2, GSK-3β, and Bcl-2. Knockdown or pharmacological inhibition of USP1 can effectively suppress tumors and is also expected to address the issues of cisplatin and poly ADP-ribose polymerase (PARP) inhibitor resistance. This review describes the structure and function of USP1 and the relationship between USP1 targets and tumors and systematically summarizes the structure-activity relationships of small molecule USP1 inhibitors disclosed from 2013 to 2023. Finally, this review discusses the challenges and opportunities in developing small molecule USP1 inhibitors.

Plant natural products have a wide range of pharmacological properties, not only can they be used as plant dietary supplements to meet the nutritional needs of the human body in the accelerated pace of life, but also occupy an important position in the research and development of therapeutic drugs for the treatment of tumors, inflammation and other diseases, and have been widely accepted by the public due to their good safety. However, despite the above advantages of plant natural products, limiting factors such as low solubility, poor stability, lack of targeting, high toxicity and side effects, and unacceptable odor have greatly impeded their conversion to clinical applications. Therefore, the development of new avenues for the application of new natural products has become an urgent problem to be solved at present. In recent years, with the continuous development of research, various strategies have been developed to improve the bioavailability of natural products. Among them, nanocarrier delivery system is one of the most attractive strategies at present. In past studies, a large number of nanomaterials (organic, inorganic, etc.) have been developed to encapsulate plant-derived natural products for their efficient delivery to specific organs and cells. Up to now, nanotechnology has not only been limited to pharmaceutical applications, but is also competing in the fields of nanofood processing technology and nanoemulsions. Among the various nanocarriers, liposomes are the largest nanocarriers with the largest market share at present. Liposomes are bilayer nanovesicles synthesized from amphiphilic substances, which have advantages such as high drug loading capacity and stability. Attractively, the flexible surface of liposomes can be modified with various functional elements. Functionalized modification of liposomes with different functional elements such as antibodies, nucleic acids, peptides, and stimuli-responsive moieties can bring out the excellent drug delivery function of liposomes to a greater extent. For example, the modification of functional elements with targeting function such as nucleic acids and antibodies on the surface of liposomes can deliver natural products to the target location and improve the bioavailability of drugs; the modification of stimulus-responsive groups such as photosensitizers, magnetic nanoparticles, pH-responsive groups, and temperature sensitizers on the surface of liposomes can achieve controlled release of drugs, localized targeting, and synergistic thermotherapy. In addition to the above properties, by using functionalized liposomes to encapsulate natural products with irritating properties can also effectively mask the irritating properties of natural products, improve public acceptance, and increase the possibility of application of irritating natural products. There are various strategies for modifying liposomes with functional elements, and the properties of functionalized liposomes constructed by different construction strategies differ. The commonly used construction strategies for functionalized liposomes include covalent modification and non-covalent modification. These two types of construction strategies have their own advantages and disadvantages. Covalent modification has better stability than non-covalent modification, but its operation is cumbersome. With the above background, this review focuses on the three typical problems faced by plant natural products at present, and summarizes the specific applications of functionalized liposomes in them. In addition, this paper summarizes the construction strategies for building different types of functionalized liposomes. Finally, this paper will also review the opportunities and challenges faced by functionalized liposomes to enter clinical therapy, and explore the opportunities to overcome these problems, with a view to better realizing the precise control of plant nanomedicines, and providing ideas and inspirations for researchers in related fields as well as relevant industrial staff.