A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

"Weibing" is a fundamental concept in traditional Chinese medicine (TCM), representing a transitional state characterized by diminished self-regulatory abilities without overt physiological or social dysfunction. This perspective delves into the biological foundations and quantifiable markers of Weibing, aiming to establish a research framework for early disease intervention. Here, we propose the "Health Quadrant Classification" system, which divides the state of human body into health, sub-health, disease-susceptible state, and disease. We suggest the disease-susceptible stage emerges as a pivotal point for TCM interventions. To understand the intrinsic dynamics of this state, we propose laboratory and clinical studies utilizing time-series experiments and stress-induced disease susceptibility models. At the molecular level, bio-omics technologies and bioinformatics approaches are highlighted for uncovering intricate changes during disease progression. Furthermore, we discuss the application of mathematical models and artificial intelligence in developing early warning systems to anticipate and avert the transition from health to disease. This approach resonates with TCM's preventive philosophy, emphasizing proactive health maintenance and disease prevention. Ultimately, our perspective underscores the significance of integrating modern scientific methodologies with TCM principles to propel Weibing research and early intervention strategies forward.

Hyssopus cuspidatus is an authentic medicinal herb used in Xinjiang， rich in the chemical constituents including flavonoids， phenolic acids and terpenoids. It possesses anti-inflammatory， antioxidant， and immunomodulatory effects. Modern pharmacological studies have demonstrated that H. cuspidatus exerts therapeutic effects on asthma by inhibiting airway inflammatory responses， suppressing airway remodeling， modulating the function of the hypothalamic-pituitary-adrenal axis， and relaxing bronchial smooth muscle. It also demonstrates intervention effects on chronic obstructive pulmonary disease by reducing levels of inflammatory cytokines and regulating immune balance. Additionally， H. cuspidatus can mitigate acute lung injury by inhibiting oxidative stress and intervene in lung cancer by suppressing proliferation and promoting apoptosis of lung cancer cells. In terms of clinical application， compound preparations containing H. cuspidatus， such as Hanchuan zupa granules and Luo’ou kezupa， have demonstrated favorable therapeutic effects on pulmonary diseases including asthma， cough， and pediatric bronchopneumonia. Currently， the research on precise action targets and compound matching rules of H. cuspidatus remains inadequate. Future studies should integrate modern technologies such as metabolomics to conduct in-depth exploration， thereby promoting the modernized development and clinical application of this traditional medicinal herb.

Objective: To analyze the trend in disease burden of stroke in Linping District, Hangzhou City from 2014 to 2023, so as to provide the basis for prevention and control of stroke. Methods: Data on incidence and mortality of stroke in Linping District from 2014 to 2023 were collected through the Chronic Disease and Death Cause Monitoring System of Hangzhou Center for Disease Control and Prevention. The disease burden was evaluated by calculating years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life years (DALY) with reference to the methodology of the Global Burden of Disease Study, and standardized using the data of the seventh national population census in 2020. The trend was analyzed using average annual percent change (AAPC). The disease burden of stroke attributed to risk factors was calculated. Results: The crude incidence of stroke was 298.13/105 and the crude mortality was 62.72/105 in Linping District from 2014 to 2023. The YYL, YLD and DALY caused by stroke were 49 413.60, 8 197.68, and 57 611.28 person-years, respectively, with decreasing trends in YLL and DALY, and an increasing trend in YLD (AAPC=-12.663%, -10.427% and 3.035%, all P<0.05). The standardized YLL rate, standardized YLD rate and standardized DALY rate were 9.54‰, 1.53‰ and 11.07‰, respectively, showing decreasing trends (AAPC=-16.011%,-0.975% and -13.791%, all P<0.05). Higher standardized DALY rate (P<0.05) and slower decline were seen in men than in women (AAPC=-13.025% vs. -14.550%, both P<0.05). The highest DALY of stroke was attributed to combined risk factors (men, 18 754.05 person-years; women, 13 256.60 person-years), followed by hypertension (men, 12 231.23 person-years; women, 9 373.77 person-years). The DALY of stroke attributed to smoking was 15.67 times higher in men than in women, and the DALY of stroke attributed to a lack of exercise was 1.27 times higher in women than in men. Conclusion There was an overall decreasing trend in the disease burden of stroke in Lingping District from 2014 to 2023, with a higher disease burden in men. The coexistence of multiple risk factors had a greater impact on stroke.

Objective To investigate the effect of continuous intraoperative insulin infusion on my-ocardial blood perfusion after cardiac surgery under cardiopulmonary bypass(CPB).Methods Forty-eight patients,21 males and 27 females,aged 55-80 years,BMI 18-28 kg/m2,ASA physical status Ⅱ-Ⅳ,who underwent elective cardiac surgery with CPB were selected and randomly divided into two groups:the insulin group(group I,n = 25)and the control group(group C,n = 23).The same anesthesia protocol was implemented in both groups.After induction of anesthesia,group Ⅰ received intravenously infusion of in-sulin 30 mU·kg-1·h-1,glucose 0.12 g·kg-1·h-1,and potassium chloride 0.06 mmol·kg-1·h-1,and group C received saline 10 ml/h,all of which were infused until the end of surgery.The targeted blood glucose range for both groups was set at 6.1-11.1 mmol/L.Transesophageal echocardiography(TEE)was performed 10 minutes after induction of general anesthesia(T2)and before the end of surgery(T6)to ex-amine the coronary sinus(CS)flow spectrum and diameter,pulmonary venous flow spectrum,and calculate CS net antegrade flow velocity time integral(VTI).Femoral mean arterial pressure(MAP),central venous pressure(CVP),stroke volume(SV),cardiac index(CI)and peripheral vascular resistance index(SVRI)were recorded at T2,2 minutes before CPB(T3),the end of CPB(T5),and T6.The concentra-tions of blood glucose and lactate 5 minutes before anesthesia induction(T1),T3,30 minutes after CPB(T4),T5,T6,6 hours after surgery(T7),12 hours after surgery(T8),and 24 hours after surgery(T9)were recorded.The levels of high-sensitivity C-reactive protein(hs-CRP),high-sensitivity troponin I(hs-TnI),and creatine kinase isoenzyme(CK-MB)were recorded 1 day preoperatively,1 and 2 days post-operatively.Results Compared with group C,in group I,CS net antegrade flow VTI and blood flow per minute were significantly increased(P<0.05),and pulmonary venous peak atrial reversal wave velocity(ARp)was significantly reduced at T6(P<0.05),SV and CI were significantly increased and SVRI was significantly decreased at T5 and T6(P<0.05),lactate concentration was significantly decreased at T7 and T8(P<0.05),hs-CRP and CKMB were significantly decreased 1 and 2 days postoperatively(P<0.05),hs-TnI was significantly reduced 2 days postoperatively(P<0.05).Conclusion Continuous insulin admin-istration during cardiac surgery with CPB while maintaining blood glucose at 6.1-11.1 mmol/L can enhance myocardial blood perfusion,mitigate postoperative inflammatory response,and reduce myocardial injury.

Objective To systematically retrieve and integrate the best evidence of enteral and parenteral nutrition support in adult patients with severe bums.Methods 2 nursing master students who had studied evidence-based nursing systematically searched the clinical decisions,recommended practices,guidelines,expert consensuses,systematic reviews,evidence summaries and other evidences on enteral and parenteral nutrition support for adult patients with severe bums in domestic and foreign guideline networks,relevant institutional websites and databases.The retrieval time was from the establishment of the databases to April 2023.2 researchers who had obtained master's degrees and undergone systematic evidence-based training in Fudan University used the appraisal of guidelines for research and evaluation n and JBI critical appraisal tools to evaluate the methodological quality,and extracted and summarized the evidence according to the theme.Results A total of 28 articles were included,including l clinical decision,9 guidelines,3 expert consensuses,9 systematic reviews,and 6 evidence summaries.A total of 20 pieces of evidence were summarized from 6 aspects:nutritional risk screening and assessment,energy requirement calculation,timing and route of nutritional support,nutrient intake,nutritional support monitoring and effect evaluation.Conclusion The best evidence of enteral and parenteral nutrition support for adult patients with severe burns summarized in this study is more comprehensive and scientific.It is suggested that in clinical application,targeted screening should be carried out according to the promotion and hindering factors of evidence,so as to scientifically carry out nutritional support for adult patients with severe burns.

Henoch-Sch?nlein purpura is also known as IgA vasculitis. The kidney involvement, namely Henoch-Sch?nlein purpura nephritis (HSPN), is one of IgA vasculitis's main clinical manifestations. Galactose-deficient IgA1 plays an important role in the pathogenesis of HSPN, which not only is similar to the "four-hits hypothesis" of IgA nephropathy, leading to IgA1 deposit in the mesangial region of the kidney, but also is closely related to inflammation with more complicated compositions of its immune complex. Therefore, abnormal glycosylation of IgA1 is expected to be a biomarker for diagnosis and prediction of HSPN pathogenesis, disease activity determination and prognosis prediction. Here, the paper reviews the research progress on the pathogenesis and clinical application of abnormal glycosylation of IgA1 in HSPN.

Objective:To explore the impact of intradialytic hypotension (IDH) on brain component volume, as well as its relationship with depression and cognitive function changes in maintenance hemodialysis patients.Method:It was a cross-sectional observational study. Clinical data of 119 patients under maintenance hemodialysis in Peking Union Medical College Hospital from July 2013 to July 2014 were collected, retrospectively. Patients were divided into IDH group and non-IDH group. 3.0T Magnetic resonance imaging examination of the head for all patients was completed and the results of volume analysis of each component of the brain were extracted. Cognitive function was assessed by the Chinese version of the simplified mental state examination scale (C-MMSE) and the Chinese version of the Montreal cognitive assessment scale (C-MoCA). Depressive status was assessed by the Hamilton depression scale 17 (HAMD_17) and living ability was assessed by the Alzheimer's disease collaborative study-daily living ability assessment questionnaire. In addition, the Philadelphia word learning test was used to measure memory, the Boston naming test to measure language, the connection test A and B to measure executive ability, and the Stroup test C to measure attention. The differences in brain component volume, cognitive function, emotion, and life ability between two groups of patients were compared, and the correlation between IDH and brain component volume was explored by regression analysis.Result:A total of 119 patients were included in this study, of whom 22 (18.5%) had hypotension during dialysis. The volumes of amygdala, cuneiform lobe, and posterior cingulate gyrus in IDH group were significantly smaller than those in the non-hypotension group [ (1.6±0.2) mm 3vs. (1.7±0.2) mm 3, t=2.674, P=0.009; (6.9±0.8) mm 3vs. (7.4±1.0) mm 3, t=2.187, P=0.031; (6.9±0.8) mm 3vs. (7.4±0.9) mm 3, t=2.252, P=0.024]. The differences of gray matter, white matter volume between the two groups showed a similar trend but did not reach statistical significance. And lacunar infarction and cerebral microbleeds were more common in IDH group. The daily living ability scores of the two groups were similar (65.51±11.52 vs. 65.71±11.53, Z=-0.456, P=0.648). The proportion of patients with cognitive abnormalities was higher in the IDH group, without statistical significance. The proportion of depression was similar. Univariate linear regression analysis showed that IDH was significantly negatively correlated with the volume of amygdala, cuneiform cortex, and posterior cingulate gyrus, which control emotions in the brain ( B=-0.117, 95% CI -0.203--0.030, P=0.009; B=-0.484, 95% CI -0.923--0.046, P=0.031; B=-0.485, 95% CI -0.911--0.058, P=0.026). After multivariate adjustment, decreased amygdala volume was still correlated with IDH ( B=-0.111, 95% CI -0.198--0.025, P=0.026). Conclusion:Recurrent IDH may lead to atrophy of various brain components, which may be one of the reasons for cognitive and emotional changes in maintenance hemodialysis patients.

BACKGROUND: B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. METHODS: Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. RESULTS: In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS. CONCLUSION: Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. REGISTERATION Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).