As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM_2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM_2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM_2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM_2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.

Objective:To investigate the patterns of mutation evolution in patients with acute myeloid leukemia (AML) during treatment and the possible clinical significances.Methods:A retrospective case series study was conducted. A total of 103 AML patients who were hospitalized at the Affiliated Yuebei People's Hospital of Medical College of Shantou University from November 2019 to August 2021 and underwent high-throughput next-generation sequencing (NGS) technology to detect the mutations of 128 AML-related genes in bone marrow samples were selected. Based on the NGS results, the somatic gene mutations in samples of patients collected at initial diagnosis (73 cases), complete remission (CR) (30 cases), non-remission (NR) (23 cases), and recurrence (12 cases) were analyzed, and the targeted drugs involved in the gene mutations detected in NR and recurrence samples were summarized.Results:The median age [ M ( Q1, Q3)] of onset for 103 patients was 58 (48, 66) years, including 64 males (61%) and 39 females (39%); 86 cases (83%) were primary AML, and 17 cases (17%) were secondary AML; at the initial diagnosis, 51 cases (50%) had normal karyotypes, 34 cases (33%) had abnormalities, and 18 cases (17.5%) were unknown. Compared with the CR samples, the mutation frequencies of FLT3 [29% (21/73) vs. 3% (1/30)], NPM1 [27% (20/73) vs. 3% (1/30)], NRAS [22% (16/73) vs. 3% (1/30)], and IDH2 [14% (10/73) vs. 0 (0/30)] were all higher in the initial diagnosis samples, and the differences were statistically significant (all P < 0.05); compared with the initial diagnosis sample, the median number of gene mutations in each CR sample was lower [4 (2, 5) vs. 7 (5, 9)], and the difference was statistically significant ( P < 0.001). However, there was no statistically significant difference in the median number of gene mutations in each patient between the initial diagnosis samples and the NR samples, the initial diagnosis samples and the recurrence samples, and the NR samples and the recurrence samples (all P > 0.05). Analysis of 14 patients with NGS data at initial diagnosis and CR showed that the same gene mutations could be detected at initial diagnosis and CR, such as DNAH23 (3 cases), USH2A (3 cases), etc; partial gene mutations were detected at initial diagnosis but were not detected at CR, including NRAS (5 cases), FLT3 (3 cases), ANKRD26 (3 cases), NPM1 (3 cases), ETV6 (3 cases), etc; ARID1B (1 case) and DNMT3A (1 case) were negative for mutations at initial diagnosis but positive upon reaching CR. Analysis of 14 patients with NGS data at initial diagnosis and NR showed that most gene mutations persisted at initial diagnosis and NR, such as DNMT3A (5 cases), NRAS (5 cases), KRAS (3 cases), RUNX1 (3 cases), etc; the mutant genes detected at initial diagnosis but not detected at NR included USH2A (2 cases), PCLO (2 cases), ATM (2 cases), FAT1 (2 cases), etc; partial gene mutations were not detected at initial diagnosis but were detected at NR, such as FAT1 (2 cases), TCF3 (2 cases), etc. Analysis of 5 patients with NGS data at CR and recurrence showed that some gene mutations were detected at both CR and recurrence, such as BCORL1 (1 case), ARID2 (1 case), SETD2 (1 case), VEGFC (1 case), etc; FLT1 (1 case) and GNAS (1 case) gene mutations were detected at CR but not detected at recurrence; at recurrence, some gene mutations that were not detected at CR were also detected, such as ANKRD26 (1 case), WT1 (1 case), etc. Among the 23 NR samples and 12 recurrence samples, the targets of drugs approved by US Food and Drug Administration or in clinical trials were detected in 14 (61%) and 5 (42%) samples respectively, including IDH1, IDH2, FLT3, KIT, KRAS, NRAS, SF3B1, U2AF1, and SRSF2. Conclusions:The number of gene mutations in AML patients during CR is significantly less than that at initial diagnosis, some gene mutations disappear when CR is achieved through treatment, but the majority of gene mutations persist during the treatment period, including NR and recurrence, suggesting that monitoring through NGS technology can help understand the evolution of gene mutations during AML treatment and discover the potential therapeutic targets.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Direct electrical stimulation of the human cortex can produce subjective visual sensations, yet these sensations are unstable. The underlying mechanisms may stem from differences in electrophysiological activity within the distributed network outside the stimulated site. To address this problem, we recruited 69 patients who experienced visual sensations during invasive electrical stimulation while intracranial electroencephalography (iEEG) data were recorded. We found significantly flattened power spectral slopes in distributed regions involving different brain networks and decreased integrated information during elicited visual sensations compared with the non-sensation condition. Further analysis based on minimum information partitions revealed that the reconfigured network interactions primarily involved the inferior frontal cortex, posterior superior temporal sulcus, and temporoparietal junction. The flattened power spectral slope in the inferior frontal gyrus was also correlated with integrated information. Taken together, this study indicates that the altered electrophysiological signatures provide insights into the neural mechanisms underlying subjective visual sensations.
Humans ; Male ; Female ; Adult ; Visual Perception/physiology* ; Electric Stimulation ; Middle Aged ; Young Adult ; Electrocorticography ; Electroencephalography ; Brain Mapping

Investigator initiated trial （IIT） represents a primary format for clinical research in traditional Chinese medicine （TCM）. As key implementation sites for TCM-based IIT targeting malignant tumors， western medicine institutions often face unique challenges in conducting such studies， which limit their feasibility and standardization. This paper reviews the registration status of TCM-based IIT for malignancies conducted in western medical institutions and analyzes key difficulties， including complex project initiation and management processes， limited TCM knowledge and skills among western medicine physicians， and relatively low patient acceptance of TCM. From a practical perspective， the study proposes several optimization strategies. These include improving the review and management mechanisms of TCM-related IIT within western medical institutions， establishing multidisciplinary clinical research teams that integrate TCM and western medicine， and enhancing investigators' training in TCM theory and clinical skills. Additionally， the study suggests standardizing IIT operational procedures， objectifying the collection of TCM diagnostic information， refining subject recruitment methods， and increasing TCM involvement in patient follow-up and management. These investigator-oriented， TCM-featured， and operable strategies aim to promote the high-quality development of TCM-based IIT in western medicine institutions and enhance the clinical application of TCM.

Objective To investigate the proportion of Th17 cells,Th1-like Th17 cells and FoxP3+Th17 cells in bone marrow of patients with myelodysplastic syndrome(MDS),the expression of interleukin-17A(IL-17A)in bone marrow supernatant and its clinical significance.Methods Forty MDS patients(MDS group)and 18 patients with nutritional anemia(control group)were selected.MDS patients were classified into the low blast(MDS-LB)group(19 cases)and the increased blast(MDS-IB)group(21 cases,including 11 cases of type IB1 and 10 cases of type IB2)based on morphological definition.The MDS patients were scored according to the revised International Prognostic Scoring System(IPSS-R),with 18 cases in the low-risk group(≤4.5)and 22 cases in the high-risk group(>4.5).Flow cytometry was used to detect the proportion of Th17 cells,Th1-like Th17 cells and FoxP3+Th17 cells in bone marrow of the MDS group and the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of IL-17A in bone marrow supernatant of the above samples.Results The proportion of Th17 cells and the level of IL-17A were higher in patients of the MDS group than those in the control group(P＜0.05).According to the median expression level of IL-17A,the MDS group was divided into the low-expression group(＜13.71 ng/L,20 cases)and the high-expression group(≥13.71 ng/L,20 cases).Compared with the low-expression group,there were higher proportion of patients with blast cells＜5%and low-risk patients(P＜0.05)in the high-expression group.Compared with the IL-17A low-expression group,the IL-17A high-expression group had a higher proportion of patients with blast cells＜5%and relatively low-risk patients(P＜0.05).Compared with the low-risk patients,high-risk patients had a lower proportion of Th17 cells,IL-17A levels and Th1-like Th17 cells,and a higher proportion of FoxP3+Th17 cells(P＜0.05).Compared with the MDS-LB group,the MDS-IB group had a lower proportion of Th17 cells,IL-17A levels and Th1-like Th17 cells,and a higher proportion of FoxP3+Th17 cells(P＜0.05).Conclusion The proportion of Th17 cells and the level of IL-17A are significantly increased in MDS patients.The decreased proportion of Th1-like Th17 cells and the increased proportion of FoxP3+Th17 cells may be related to the increased proportion of blast cells and higher risk stratification in patients.

Objective:To evaluate the safety and efficacy of the TiRobot assisted screw placement in patients with lumbar degenerative diseases.Methods:The clinical data of 165 patients with lumbar degenerative diseases from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyze, and all patients were treated with posterior lumbar decompression and instrumentation. Among them, 46 patients were used the TiRobot assisted screw placement during surgery (robotic-assisted group), and 119 patients underwent freehand screw placement by C-arm X-ray machine fluoroscopy (freehand group). The operation time, intraoperative blood loss, complication and skelalgia visual analogue scale (VAS), Oswestry disability index (ODI) before and after operation were recorded. The accuracy of screw placement and rate of proximal facet joint violation were compared between two groups.Results:There were no statistical difference in operation time, intraoperative blood loss and incidence of complication between two groups ( P>0.05). In the two groups, the 3 d VAS and ODI after operation were significantly lower than those before operation, robot-assisted group: (3.33 ± 1.40) scores vs. (6.54 ± 2.00) scores and (16.96 ± 8.03) scores vs. (43.09 ± 5.48) scores; freehand group: (3.56 ± 1.29) scores vs. (6.55 ± 1.65) scores and (18.89 ± 6.74) scores vs. (44.91 ± 4.96) scores, and there were statistical differences ( P<0.01); there were no statistical difference in VAS and ODI before operation and 3 d after operation between two groups ( P>0.05). A total of 234 screws were implanted in robot-assisted group, and 590 screws were implanted in freehand group. The accuracy of screw placement in robot-assisted group was significantly higher than that in freehand group: 80.77% (189/234) vs. 74.58% (440/590), the rate of proximal facet joint violation was significantly lower than that in freehand group: 2.56% (6/234) vs. 7.29% (43/590), and there were statistical differences ( χ2 = 3.56 and 6.68, P<0.05). Conclusions:The TiRobot assisted screw placement for lumbar degenerative diseases is safe and effective. Compared to freehand technique, the TiRobot assisted method demonstrates higher screw placement accuracy and a lower rate of proximal facet joint violation.

Objective To study the relationship between the expression of long non-coding RNA lung adenocarcinoma metastasis-associated transcript 1(lncRNA MALAT1)and microRNA(miR)-181a-5p in lung adenocarcinoma tissues and the signal pathway of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3),clinicopathological features and prognosis.Methods 218 patients with lung adenocarcinoma who had surgical resection at our institution between January 2018 and May 2021 had their cancer tissues and nearby normal lung tissues collected,the levels of lncRNA MALAT1,miR-181a-5p and key factors of JAK2/STAT3 signaling pathway(JAK2 mRNA,STAT3 mRNA)in lung adenocarcinoma tissues and adjacent tissues were detected by reverse transcription polymerase chain reaction(RT-PCR).The correlation between the expression levels of lncRNA MALAT1 and miR-181a-5p in cancer tissues of lung adenocarcinoma patients and the levels of key factors in JAK2/STAT3 signaling pathway were analyzed by Pearson test.The relationship between the expression levels of lncRNA MALAT1 and miR-181a-5p and the clinicopathological features of lung adenocarcinoma patients were analyzed.Patients with lung adenocarcinoma were followed up for 3 years,and their prognosis was counted,the 3-year overall survival rate of lncRNA MALAT1 and miR-181a-5p low/high expression groups were analyzed by Kaplan-Meier method.The prognostic factors were analyzed by univariate and multivariate COX risk proportional regression models.Results In lung adenocarcinoma tissues,the expression levels of lncRNA MALAT1,JAK2,and STAT3 mRNA were substantially greater(P＜0.05)than in neighboring normal lung tissues,whereas the expression level of miR-181a-5p was significantly lower(P＜0.05)in compared to nearby normal lung tissues.Pearson test results showed that,lncRNA MALAT1 was positively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=0.526、0.483),and miR-181a-5p was negatively correlated with JAK2 and STAT3 mRNA expression levels in cancer tissues of patients with lung adenocarcinoma(P＜0.05,r=-0.430、-0.493).lncRNA MALAT1 had a considerably greater expression rate and miR-181a-5p had a significantly lower expression rate in patients with TNM stage Ⅲa,lymph node metastasis and poorly differentiated lung adenocarcinoma than in patients with TNM stage Ⅰ-Ⅱ,without lymph node metastasis and moderately well differentiated lung adenocarcinoma(P＜0.05).Three patients were lost during the 3-year follow-up of 218 patients with lung adenocarcinoma,and the 3-year overall survival rate was 58.14％(125/215).The 3-year overall survival rate of the lncRNA MALAT1 high expression group was considerably lower than that of the lncRNA MALAT1 low expression group.The miR-181a-5p high expression group had a substantially greater(P＜0.05).Lymph node metastasis,TNM stage Ⅲ a,decreased expression level of miR-181a-5p,and increased expression level of lncRNA MALAT1 are risk factors for the prognosis of patients with lung adenocarcinoma(P＜0.05).Conclusion The low expression of miR-181a-5p and the high expression of lncRNA MALAT1 in lung adenocarcinoma tissues are related to TNM stage Ⅲa,lymph node metastasis and poor prognosis,which may promote the progression of lung adenocarcinoma and cause poor prognosis by activating JAK2/STAT3 signaling pathway.