Background The internet has become an important channel for the public to obtain information on e-cigarettes, and online attention toward e-cigarettes may reflect, to some extent, the level of public cognition and interest, carrying significant public health implications. Objective To analyze the online attention toward e-cigarettes among the Chinese public and reveal its spatiotemporal trends, providing a scientific basis for the formulation of e-cigarette regulatory policies. Methods Based on data from the Baidu Index platform, the daily average search index data for netizens across various provinces in China from 2018 to 2024 were obtained as a quantitative measure of e-cigarette online attention by using “e-cigarette + electronic cigarette” as search terms. The seasonal concentration index was applied to examine the degree of monthly concentration of attention, and global spatial autocorrelation (Global Moran’s I) was used to characterize the overall spatial clustering pattern of e-cigarette online attention at the provincial scale. Results From 2018 to 2024, the overall online attention toward e-cigarettes in China was 3650, 4271, 5112, 7109, 4345, 2603, and 1527 times·d⁻¹, respectively, with the seasonal concentration index narrowing over time (from 0.885 in 2018 to 0.817 in 2024). Peak months for online attention were concentrated in March and November, while levels were lower in August and December. The provinces with higher per capita e-cigarette online attention were mainly located in the eastern and western regions. In general, the global Moran's I values for e-cigarette online attention in China from 2018 to 2024 were 0.194, 0.154, 0.184, 0.173, 0.166, 0.159, and 0.146, respectively, indicating positive spatial autocorrelation. Conclusion Significant spatiotemporal disparities are observed in the e-cigarette online attention in China. Temporally, overall network attention exhibits an “increase-then-decrease” trend. Spatially, the per capita attention demonstrates a distinct pattern characterized by higher levels in the eastern and western regions and lower levels in the central regions. These findings underscore the need for targeted e-cigarette regulatory policies tailored to specific time periods and geographic regions.

The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

Sonodynamic therapy （SDT） applies low-frequency ultrasound to activate sonosensitizers that have accumulated in tumor location， which induces cavitation effects and leads to the in-situ generation of reactive oxygen species （ROS）， thereby achieving precise and efficient tumor treatment. Owing to its advantages such as deep tissue penetration and controllable treatment range， SDT has attracted significant attention and has been widely used in the research on the treatment of various tumors. While conventional treatment modalities have achieved significant efficacy in the treatment of hepatocellular carcinoma （HCC）， there are still certain limitations. In this context， nanomedicine-based SDT leverages the targeting capabilities of nano-agents to realize specific killing of HCC cells， and furthermore， it can synergize with photodynamic therapy， chemotherapy， and immunotherapy to provide new opportunities for developing novel treatment modalities for HCC. This article reviews the mechanism of action of SDT and the advances in the research and application of SDT in the treatment of HCC， analyzes the shortcomings of existing studies， and proposes the directions for future development， in order to provide a theoretical foundation and scientific guidance for related research on HCC.

ObjectiveAutoimmune thyroiditis （AIT） is a complex and immune-mediated disorder， with no established treatment protocol. Both Western and traditional Chinese medicine （TCM） focus on the pathogenesis and treatment of AIT. This study evaluated the clinical consistency of existing AIT animal models based on the diagnostic criteria of both Western and TCM， using a novel evaluation method. Additionally， it proposed recommendations and future prospects for improving these models. MethodsA comprehensive literature review was conducted on existing AIT animal models， using databases and the diagnostic criteria of both Western and TCM. Core and accompanying symptoms of these models were scored based on the diagnostic criteria of both Western and TCM， and clinical consistency was assessed. ResultsMice are the primary experimental animals used in AIT modeling. Modeling methods include vaccine immunization， iodine induction， heterologous thyroid antigen immunization， and a combination of high iodine water and antigen immunization. The average consistency of clinical syndromes based on TCM and Western medicine is 40%， 60%， 54%， and 63%， with the highest consistency observed in the combined high iodine water and antigen immunization model. Pathological models based on TCM are less common， with the liver-stagnation-spleen-deficiency rat model showing high clinical consistency. While most models are designed according to Western medical theory， meeting the surface and structural effectiveness criteria of Western medicine. However， there is a lack of fine-tuning and clear differentiation of TCM syndromes. ConclusionCurrent AIT syndrome-disease combination animal models primarily reflect the pathological features of Western medicine， with limited integration of TCM syndromes. Future research should aim to combine the syndrome characteristics of TCM with the pathological features of Western medicine， creating multi-factor and dynamic syndrome-disease models. Such models would better facilitate an experimental platform that conforms to the theories of TCM， providing more comprehensive support and guidance for the pathogenesis and treatment strategies of AIT.

Objective To investigate the effects of a 100 mT static magnetic field(SMF)on emotional behavior and brain damage-related molecules in mice.Methods Fifty-eight C57BL/6N mice were randomly divided into control group(n=25)and observation group(n=33).Mice in observation group were exposed to a 100 mT SMF for 0.5 h/d over 14 consecutive days,while mice in control group underwent pseudo-exposure.On the 7 and 14 days of exposure,anxiety-like behavior was assessed using open field and elevated plus maze tests.Cerebral blood flow was monitored using laser speckle imaging,and the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-4,central nervous system specific protein β(S100β),neuron-specific enolase(NSE),and brain-derived neurotrophic factor(BDNF)were measured by radioimmunoassay.BDNF expression in the brain was detected by immunofluorescence.Results On the 7 and 14 days of SMF exposure,the open field and elevated plus maze tests showed no statistically significant differences between observation and control groups in the frequencies,durations,and distance entering the central area of the open field and the open arm of the elevated plus maze(P>0.05).Laser speckle imaging revealed no significant difference in cerebral cortical perfusion compared with pre-exposure period(P>0.05).The results of radioimmunoassay showed that compared with control group,on the 7 d of SMF exposure,the serum IL-1β,NSE and S100β levels were significantly increased(P<0.05),the serum BDNF level was significantly decreased(P<0.05),and the IL-1β and TNF-α contents in brain tissues were significantly increased in observation group(P<0.01).On the 14 d of SMF exposure,serum IL-1β,TNF-α,NSE,and S100β levels were significantly increased(P<0.05,P<0.0001),and the brain IL-1β and TNF-α levels were significantly increased(P<0.01)in observation group.No statistically significant differences were found in anti-inflammatory cytokine IL-4 level of serum and brain tissue or BDNF content of brain tissue between the two groups(P>0.05).Conclusion Continuous exposure to a 100 mT SMF for 14 d at 0.5 h/d induces neuroinflammation and brain damage in mice,without inducing anxiety-like behavior.

Objective To observe the difference of bone micro-structure in different regions of proximal femur,micro-CT scanning was performed on 30 proximal femur specimens to explain the mechanism of proximal femur fracture and to provide anatomical basis for prosthesis design.Methods Totally 30 intact proximal femur specimens were obtained from 60-80 year-old cadavers.Micro-CT scanning was used to measure the trabecular thickness(Tb.Th),trabecular number(Tb.N),trabecular space(Tb.Sp),connectivity(Conn)and bone mineral density(BMD)and other parameters in 7 regions of proximal femur,including proximal pressure trabecular(PPT),distal pressure trabecular(DPT),femoral head-neck junction(FHNJ),head and neck of femoral neck(HNFN),the base of femoral neck(BPFN),intertrochanteric line(IL)and greater trochanter(GT).Results The bone mineral density of IL and GT were higher than those of BPFN,FHNJ,DPT and PPT.The trabecular thickness of GT was the largest,followed by IL,BPFN and HNFN,and the smallest was FHNJ,DPT and PPT.The trabecular space of IL was larger than that of GT,and the data of both were larger than those of other parts,among which DPT and PPT were the smallest.The trabecular number of IL and GT were the smallest,BPFN,HNFN and FHNJ were larger,and DPT was the largest.The volume fraction of IL was the smallest,BPFN and HNFN were larger,DPT and PPT were the largest.Conclusion The bone density,trabecular thickness,bone volume,and total volume of GT and IL in the proximal femur of elderly patients are all relatively large,so the reason for the high incidence of fractures is not due to weak internal bone microstructure;The bone density,trabecular thickness,and trabecular gap at the proximal and distal ends of the vertical trabecular bone are relatively small.If it is necessary to perform core decompression for prosthesis filling at this location,the design should be conducive to the mechanical conduction of the prosthesis and the regeneration of surrounding bone tissue.

Objective To investigate the value of secreted frizzled-related protein 1(SFRP1),GATA binding protein 3(GATA3)combined with human papillomavirus deoxyribonucleic acid(HPV-DNA)in predicting the risk of postoperative recurrence of high-grade cervical intraepithelial neoplasia(CIN)with positive thin-prep cytologic test(TCT).Methods A total of 200 patients with high-grade CIN and positive TCT results from July 2021 to July 2023 were selected as study subjects.All patients underwent cervical conization,and were divided into recurrence group and non-recurrence group according to the recurrence status one year after surgery.The clinical data,HPV-DNA viral load,and the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cer-vical tissues were compared between the two groups.The HPV-DNA viral load,SFRP1 mRNA,and GATA3 mRNA expression levels in patients with different CIN grades were compared,and their cor-relations with CIN grade and the risk of postoperative recurrence were analyzed.The predictive val-ues of SFRP1,GATA3,and HPV-DNA for the risk of postoperative recurrence were analyzed.Results Among 200 patients,2 were lost during the follow-up period.The recurrence group(n=30)had higher proportions of CIN grade Ⅲ,glandular involvement,positive surgical margins,high-risk human papillomavirus(HPV),higher HPV-DNA viral load,and a higher proportion of HPV positivity at 6 months after surgery compared with the non-recurrence group(n=168),and the differences were statistically significant(P＜0.05).The relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues of the recurrence group were lower than those of the non-recur-rence group,and the differences were statistically significant(P＜0.001).The HPV-DNA level in pa-tients with CIN grade Ⅲ was higher than that in those with CIN grade Ⅱ,and the relative expres-sion levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were lower than those in patients with CIN grade Ⅱ,and the differences were all statistically significant(P＜0.001).Spearman cor-relation analysis showed that HPV-DNA was positively correlated with CIN grade(P＜0.001),while the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were neg-atively correlated with CIN grade(P＜0.001).Logistic regression analysis showed that HPV-DNA,the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were independ-ent influencing factors for the risk of postoperative recurrence(P＜0.001).The receiver operating characteristic(ROC)curve results showed that the areas under the curve(AUCs)for predicting the risk of postoperative recurrence by HPV-DNA,the relative expression levels of SFRP1 mRNA and GATA3 mRNA in cervical tissues were 0.787,0.781,and 0.764,respectively,with sensitivities of 80.00％,76.67％,and 76.67％,and specificities of 74.40％,73.81％,and 67.26％,respec-tively.The AUC for the combined prediction of the risk of postoperative recurrence by the three indica-tors was 0.924,with a sensitivity of 80.00％and a specificity of 93.45％,which was superior to the pre-dictive values of each indicator alone(Z=3.159,3.306,4.018,P＜0.001).Conclusion HPV-DNA,SFRP1,and GATA3 in cervical tissues have certain predictive values for the risk of postoperative re-currence in patients with high-grade CIN and positive TCT results,and combined detection can im-prove the predictive efficacy.