BACKGROUND:Currently,exercise therapy is an effective non-pharmacological treatment for low back pain,and exercise therapy can maintain lumbar spine stabilization through mechanical-chemical coupling between bones and muscles,but there is no clear description of the research progress and optimal treatment protocols for exercise therapy to relieve chronic non-specific lower back pain through mechanical-chemical coupling. OBJECTIVE:To review the research progress related to the influence of paravertebral muscles on lumbar spine stabilization during exercise therapy through mechanical-chemical coupling,which in turn relieves chronic non-specific lower back pain,as well as the current optimal treatment protocols of exercise therapy for chronic non-specific lower back pain. METHODS:Literature searches were performed in WanFang database,CNKI,VIP,Web of Science,and PubMed database,with search terms of"chronic non-specific low back pain,lumbar spine stabilization,paravertebral muscles,exercise therapy"in Chinese and English.Relevant literature published from database inception to January 2024 was searched and 93 articles were included for final summarization. RESULTS AND CONCLUSION:Exercise therapy can act on the paravertebral muscles and bones through appropriate mechanical stimulation and produce corresponding changes.Exercise therapy is an important intervention for chronic non-specific lower back pain as it improves the quality of the paravertebral muscles,primarily through mechanical-chemical coupling,and thus maintains lumbar spine stabilization for better relief of chronic non-specific lower back pain.However,there are no clear reports on the exact effective protocols for exercise therapy to treat chronic non-specific lower back pain through lumbar spine stabilization.The development of an individualized exercise program is particularly important for the treatment and prognosis of chronic non-specific low back pain.Muscle mass and bone mass of the same individual are closely related,and imaging assessment of paravertebral muscle mass and quantity is important for disease detection and intervention.

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

OBJECTIVE To evaluate the efficacy and safety of ceftazidime/avibactam （CAZ/AVI） combined with amikacin （AMK） in the treatment of carbapenem-resistant Enterobacteriaceae （CRE） severe pneumonia. METHODS A retrospective cohort study was conducted on 240 patients diagnosed with severe pneumonia caused by CRE infection in the intensive care unit （ICU） of the Affiliated Hospital of Xuzhou Medical University from January 2022 to December 2024. The patients were divided into a combination group （CAZ/AVI combined with AMK， n＝136） and a control group （CAZ/AVI alone， n＝104）. The 28-day mortality rate， clinical efficacy，mechanical ventilation time， ICU stay， infectious markers [C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， white blood cell count （WBC）， and neutrophil percentage （N%）]， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） scores， and total incidence of adverse reactions were compared between two groups of patients. At the same time， subgroup analysis was conducted based on the severity of the condition， mechanical ventilation status， and baseline renal function. RESULTS The 28-day mortality rate of patients in the combination group was significantly lower than that in the control group （20.6% vs. 34.6%， P＝0.022）， and the clinical effective rate was significantly higher than that in the control group （80.1% vs. 65.4%， P＝0.004）. The mechanical ventilation time and ICU hospitalization time in the combination group were significantly shorter than those in the control group （[ 7.2±2.4） days vs. （10.4±3.6） days， （10.5±3.1） days vs. （13.7±3.8） days； P＜0.01].After 7 days of treatment， the CRP， PCT， IL-6， WBC， N% and APACHE Ⅱ scores of patients in the combination group significantly decreased compared to before treatment， and the decrease was significantly greater than that of the control group （P＜0.01）. There was no statistically significant difference in the total incidence of adverse reactions between the two groups of patients （11.8% vs. 13.5%， P＝0.690）. Subgroup analysis showed that among high-risk （APACHE Ⅱ score≥15） and mechanically ventilated patients， the 28-day mortality rate and weaning time of the combination group were significantly lower/ shorter than those of the control group （P＜0.05）， while there was no significant difference in the total incidence of adverse reactions between the combination group and the control group after dose adjustment in patients with chronic renal insufficiency （P＞0.05）. CONCLUSIONS The CAZ/AVI combined with AMK regimen has better anti-infective efficacy and good safety in patients with severe pneumonia caused by CRE infection compared to the CAZ/AVI regimen alone； the survival benefits of this joint regimen are more significant in high-risk and mechanically ventilated patients， with critically ill patients being the main beneficiaries.

By analysing the similarity between defense qi and leukocytes in terms of function， site of action， and circadian rhythm， it is proposed that in traditional Chinese medicine （TCM）， the pathogenesis of leukopenia is defense qi deficiency. By analyzing the relevant discussions on the generation and transmission of defense qi in TCM classics， it is believed that the original qi in lower jiao （焦） is the source of defense qi， while the water and grain qi in middle jiao enriches defense qi， and the upper jiao transmits and distributes defense qi to the whole body. Therefore， when treating leukopenia after chemotherapy with TCM， Guilu Erxian Gelatin （龟鹿二仙胶） and Yougui Pill （右归丸） are often used to tonify the kidney and supplement essence， and moxibustion at Guanyuan （CV 4） and Qihai （CV 6） is usually accompanied to replenish the original qi in lower jiao and enrich the source of defense qi. Guipi Decoction （归脾汤）， Buzhong Yiqi Decoction （补中益气汤）， Shenling Baizhu Powder （参苓白术散）， and Sijunzi Decoction （四君子汤） are often suggested to strengthen spleen and replenish qi， in combination with moxibustion at Zhongwan （CV 12） and Zusanli （ST 36） to transport the spleen and stomach in the middle jiao to enrich the defense qi. Modified Guizhi Decoction （桂枝汤） to harmonize nutrient and defensive aspects is often used， and moxibustion at Dazhui （GV 14） and Feishu （BL 13） or scraping is added to dredge the striae and interstice in the upper jiao and promote transmission and dissemination of the defense qi. Considering the whole process of generation and distribution of defense qi， it is suggested to choose the most appropriate treatment modality flexibly， and combine internal treatment with external treatment， in order to provide ideas for the treatment of leukopenia in tumour patients.

Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions, etc. Internal causes include age, sex, disease, etc. This paper analyzes and systematically combs how independent variables and covariates directly or indirectly affect the three time-related factors by affecting the body's physiology and internal environment, thus changing the complex process of Fa. Understanding this theoretical framework can better optimize the independent variables to reduce the impact of covariates on Fa. In addition, this paper also introduces the latest progress of prediction and evaluation of Fa, including the progress of complex dissolution device and the status of software prediction.

Basic research and interdisciplinary application of traditional Chinese medicine （TCM） have been continuously extended and rapidly developed with the continuous funding and promotion of basic research on TCM supported by the National Natural Science Foundation of China （NSFC）， and the overall level of basic research on TCM has been significantly improved， which has made important contributions to the diagnosis and treatment mechanism of TCM by "clarifying， identifying， and interpreting"， providing benchmark guarantees for basic research and industry development of TCM. This article focused on the application and funded projects of NSFC in 2023 under the H31 application code of TCM. It analyzed the project types， branch codes， research question categories， supporting units and regions， research directions， and keywords and summarized the characteristics of the currently funded projects in H31. At the same time， it analyzed the relevant problems in the project application process and put forward several suggestions， so as to provide a reference for scholars in the field of TCM. In 2023， a total of 8 334 applications for three types of projects （general projects， projects for young scholars， and regional projects） under the H31 code have been received by NSFC， which is the highest number in the past five years. However， the proportion of funding is still on a downward trend， and there is fierce competition among applicants. Finally， 804 projects for the three categories under the H31 code have been funded. The total funding decreased in 2022， and the average funding amount of the general project and the regional project has dropped to the lowest in the past five years. It is found that the development of branch research and the research questions under the H31 code is unbalanced. Few projects have focused on the original theory of TCM. Some projects are detached from the characteristics and research laws of TCM. Most researchers lack innovative research ideas， and the applications they write are filled with routines and patterns. In addition， the issue of scientific integrity remains a primary principle for project applicants.

Objective:To compare demographic characteristics,clinical characteristics,therapeutic characteris-tics and physiological indicators of patients with bipolar Ⅰ disorder and bipolar Ⅱ disorder.Methods:A total of 381 patients with bipolar disorder(BD)diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5 th Edi-tion(DSM-5)were selected,including 302 patients with BD-Ⅰ(79.27％),74 patients with BD-Ⅱ(19.42％)and 5 patients with other specific and related disorders(1.31％).Demographic and clinical characteristics were collected with self-designed clinical information questionnaire.Multivariate logistic regression and multivariate linear regres-sion analysis were used for analysis.Results:Compared with patients with BD-Ⅱ,patients with BD-Ⅰ had more risk to have psychotic features(OR=5.75,95％CI:2.82-11.76),longer disease duration,and more repeated transcra-nial magnetic therapy(OR=3.09,95％CI:1.02-9.35),higher uric acid,total cholesterol and high-density lipo-protein.BD-Ⅰ in Han nationality was more common(OR=11.50,95％CI:1.76-75.30),and had lower education level(OR=10.22,95％CI:1.16-89.77),and less family history of psychosis(OR=2.34,95％CI:1.01-5.42).Conclusion:There are significant differences between BD-Ⅰ and BD-Ⅱ in demographic and clinical charac-teristics,treatment status,and physiological indicators,which could provide clues for exploring the pathogenesis of bipolar disorder.

Objective:To describe the prevalence of anxiety symptom and personality disorder among medical aesthetic clients,and explore related factors of anxiety symptoms among them.Methods:Totally 788 clients who consulted in a cosmetic plastic surgery department were recruited in a tertiary hospital in Beijing from November 2021 to July 2023.Using the Personality Diagnostic Questionnaire-4(PDQ-4)and the Self-Rating Anxiety Scale(SAS)as assessment instruments,with a cutoff point of 42 and 50 points respectively,for screening out personality disorder and anxiety symptom.Statistical analysis was conducted by analysis of variance,chi-square tests,multivari-ate linear regression and logistic regression.Results:The rate of anxiety symptom among the medical aesthetic cli-ents was of 15.23％(120/788),and the prevalence of personality disorder was 3.50％(28/788).Age was nega-tively associated with SAS scores(β=-0.82,P=0.009),PDQ-4 score was positively associated with SAS score(β=0.15,P＜0.001),eye plastic surgery,facial contouring and minimally invasive plastic surgery were positively associated with SAS score(β=2.00-3.64,P＜0.05).Conclusion:The younger and the more prominent the per-sonality dysfunction the clients are,the severer anxiety symptom they have.The clients who consult for eye plastic surgery,facial contouring,and minimally invasive plastic surgery have severer anxiety symptom.

Epigenetic pathways play a critical role in the initiation, progression, and metastasis of cancer. Over the past few decades, significant progress has been made in the development of targeted epigenetic modulators (e.g., inhibitors). However, epigenetic inhibitors have faced multiple challenges, including limited clinical efficacy, toxicities, lack of subtype selectivity, and drug resistance. As a result, the design of new epigenetic modulators (e.g., degraders) such as PROTACs, molecular glue, and hydrophobic tagging (HyT) degraders has garnered significant attention from both academia and pharmaceutical industry, and numerous epigenetic degraders have been discovered in the past decade. In this review, we aim to provide an in-depth illustration of new degrading strategies (2017-2023) targeting epigenetic proteins for cancer therapy, focusing on the rational design, pharmacodynamics, pharmacokinetics, clinical status, and crystal structure information of these degraders. Importantly, we also provide deep insights into the potential challenges and corresponding remedies of this approach to drug design and development. Overall, we hope this review will offer a better mechanistic understanding and serve as a useful guide for the development of emerging epigenetic-targeting degraders.