Chinese medicinal materials serve as the material foundation of traditional Chinese medicine （TCM） culture. The sustainable development of Chinese medicinal material resources is a focal point in the modernization of TCM. With the increasing scarcity of Chinese medicinal material resources， the expansion of new Chinese medicinal material resources has become a crucial means for the sustainable utilization of these resources. New Chinese medicinal material resources refer to natural resources that have been newly discovered or developed， possessing potential medicinal value or healthcare functions， which fall outside the traditional application scope of herbal medicines. These resources have not yet been widely recognized or applied within the framework of traditional TCM theory. They specifically include artificial substitutes for endangered medicinal materials， new medicinal parts of medicinal plants， medicinal materials with expanded clinical applications， and foreign medicinal resources. The rational compatability and formulation of new Chinese medicinal material resources are essential pathways for integrating them into the TCM system. Due to the weak foundational research on new Chinese medicinal material resources in China， the characteristics of these resources that align with the TCM theory are not yet fully understood， posing numerous constraints on formulating prescriptions based on the traditional compatibility principles of TCM. This paper integrates the traditional formulation theory of TCM with modern data integration methods， proposing four formulation models for new TCM resources： synergistic compatibility， substitutive compatibility， symptom-based compatibility， and efficacy semantic compatibility. These models provide new insights for the application of new Chinese medicinal material resources， not only facilitating their rational use in clinical practice but also offering theoretical support for the development and compatibility research of these resources.

Chinese medicinal materials serve as the material foundation of traditional Chinese medicine （TCM） culture. The sustainable development of Chinese medicinal material resources is a focal point in the modernization of TCM. With the increasing scarcity of Chinese medicinal material resources， the expansion of new Chinese medicinal material resources has become a crucial means for the sustainable utilization of these resources. New Chinese medicinal material resources refer to natural resources that have been newly discovered or developed， possessing potential medicinal value or healthcare functions， which fall outside the traditional application scope of herbal medicines. These resources have not yet been widely recognized or applied within the framework of traditional TCM theory. They specifically include artificial substitutes for endangered medicinal materials， new medicinal parts of medicinal plants， medicinal materials with expanded clinical applications， and foreign medicinal resources. The rational compatability and formulation of new Chinese medicinal material resources are essential pathways for integrating them into the TCM system. Due to the weak foundational research on new Chinese medicinal material resources in China， the characteristics of these resources that align with the TCM theory are not yet fully understood， posing numerous constraints on formulating prescriptions based on the traditional compatibility principles of TCM. This paper integrates the traditional formulation theory of TCM with modern data integration methods， proposing four formulation models for new TCM resources： synergistic compatibility， substitutive compatibility， symptom-based compatibility， and efficacy semantic compatibility. These models provide new insights for the application of new Chinese medicinal material resources， not only facilitating their rational use in clinical practice but also offering theoretical support for the development and compatibility research of these resources.

As the core technology of processing， the stir-frying method of traditional Chinese medicine（TCM） realizes the regulation of efficacy of medicinal substances through the coordination of fire gradient and excipients. This study aims to systematically analyze the influence of different stir-frying degrees（stir-frying until yellow， stir-frying to brown， stir-frying to charcoal） and excipient types（solid excipients such as rice， wheat bran， soil， liquid excipients such as rice wine， vinegar， honey） on the physicochemical properties， efficacy and toxicity of TCM， summarizing their common regulatory mechanisms and characteristics. Then， the three-dimensional regulatory common mechanisms and five-dimensional regulatory specificity mechanisms of different stir-frying processes were obtained. The three-dimensional regulatory common mechanisms are as follows：①Thermal effects break down inherent barriers of medicinal materials and improve the dissolution of components. ②Inducing Maillard reaction， carbonization and other reactions of medicinal materials to promote the transformation of components. ③Combining the catalytic and harmonizing effects of excipients to achieve targeted enrichment of efficacious substances and precise control of toxic components. The five-dimensional regulatory specificity mechanisms manifest as：①The efficacy gradient pattern where stir-frying until yellow strengthens the spleen， stir-frying to brown aids digestion， and stir-frying to charcoal stops bleeding. ②According to the polarity difference and intrinsic properties， the liquid excipients form a directional synergistic mechanism of wine processing enhances ascending nature， ginger processing to warm and disperse， salt processing directs effects to the kidneys， vinegar processing targets the liver， honey processing imparts sweetness and moderation. ③Through porous structure and interfacial properties， solid excipients give the synergistic effect of rice processing for diarrhea relief， bran processing for stomach tonification， soil processing for warming the middle warmer， and clam powder/talcum powder/sand processing for texture optimization. ④Thermal effects induce decomposition/oxidation/polymerization and other reactions to reshape the material basis， directing changes in the efficacy. ⑤The targeted distribution of efficacy is regulated by component enrichment and meridian-guiding effect， and the meridian tropism is changed. The system， driven by thermal effect， excipient synergy and physicochemical reconstruction， integrates five-dimensional regulation of fire， solvent， interface， composition and distribution. It systematically explains the inherent law of efficacy-substance-process of traditional stir-frying， and provides theoretical basis and practical guidance for standardizing TCM processing and enhancing the efficacy.

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*

In recent years, the high temperature and heatwaves have seriously affected the health of Chinese residents, and there is an important need for public health protection guidelines for high temperature and heatwaves in China. The National Bureau of Disease Control and Prevention has organized experts to fully investigate the evidence from epidemiological research on the health of populations in high temperature and heatwaves globally and in China, analyze the health hazards and protection needs of different populations, and put forward practical and effective individual protection measures and health recommendations. For this reason, the "Guideline for Public Health Protection against High Temperature and Heatwaves" (referred to as the "Guideline") was officially issued in June 2023. This article interprets the background and significance of the Guideline, the principles of compilation, the main considerations, the main contents, the implementations and promotions and other aspects, to improve the understanding of the content of the Guideline and strengthen the publicity and implementations.

Objective To investigate the expression of HOXB4 gene in patients with myelodysplastic syn-dromes(MDS)and its clinical significance in disease progression.Methods mRNA expression of HOXB4 gene in bone marrow mononuclear cells was detected by real-time fluorescence quantitative PCR(RT-qPCR),and the difference in HOXB4 expression was compared between 49 patients with MDS(MDS group)and 35 patients without MDS(group C).The relationship of mRNA expression of HOXB4 with disease characteristics and clinical prognosis was explored in MDS patients.Results mRNA expression level of HOXB4 gene was higher in MDS group than that in group C(P＜0.05).The patients were divided into a high-and a low-expression group according to the median expression level of HOXB4.Leukocyte count was lower in the high-expression group in the low-expression group at the time of initial diagnosis.The proportion of patients with subtypes of primitive cellular hyperplasia,poor prognostic staging and leukemic transformation was higher in the high-expression group than in the low-expression group.Conclusions mRNA expression level of HOXB4 gene has certain relation with AML transformation in MDS patients.

In recent years, the high temperature and heatwaves have seriously affected the health of Chinese residents, and there is an important need for public health protection guidelines for high temperature and heatwaves in China. The National Bureau of Disease Control and Prevention has organized experts to fully investigate the evidence from epidemiological research on the health of populations in high temperature and heatwaves globally and in China, analyze the health hazards and protection needs of different populations, and put forward practical and effective individual protection measures and health recommendations. For this reason, the "Guideline for Public Health Protection against High Temperature and Heatwaves" (referred to as the "Guideline") was officially issued in June 2023. This article interprets the background and significance of the Guideline, the principles of compilation, the main considerations, the main contents, the implementations and promotions and other aspects, to improve the understanding of the content of the Guideline and strengthen the publicity and implementations.

Objective:To observe the effects of acupuncture and moxibustion on ubiquitin-like containing PHD and RING finger domains 1(UHRF1)and DNA methyltransferase 1(DNMT1)in ectopic endometrium of rats with endometriosis(EMS). Methods:Forty Sprague-Dawley rats were randomly divided into a sham operation group with 10 rats and a model-building group with 30 rats according to body mass.EMS rat models were established in the model-building group and then were divided into a model group,an acupuncture and moxibustion group,and a progesterone group,with 10 rats in each group.All rats were fixed by a fixator.The sham operation group and the model group were given normal saline by gavage.The acupuncture and moxibustion group received acupuncture at Xuehai(SP10)and Sanyinjiao(SP6),moxibustion at Guanyuan(CV4),and gavage of normal saline.The progesterone group was given the mixed liquid made of dydrogesterone and normal saline by gavage.After 28 d of treatments,the three diameters(length,width,and height)of EMS rats'ectopic cysts were measured,the cyst volumes were calculated,the volumes before intervention were subtracted,and the difference values were used to evaluate the growth of ectopic cysts.UHRF1 and DNMT1 mRNA and protein levels in normal endometrium,eutopic endometrium,and ectopic endometrium were detected by real-time polymerase chain reaction and immunohistochemistry. Results:There was no significant difference in the ectopic cyst volume difference between the acupuncture and moxibustion group and the progesterone group(P>0.05),but they were smaller than that of the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the ectopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of DNMT1 mRNA and UHRF1 protein in the eutopic endometrium of the model group were lower than those in the normal endometrium(P<0.05).The levels of UHRF1 mRNA and protein and the level of DNMT1 protein in the ectopic endometrium of the acupuncture and moxibustion group were higher than those in the model group(P<0.05),and the level of UHRF1 mRNA was higher than that in the progesterone group(P<0.05).The level of DNMT1 mRNA in the eutopic endometrium of the acupuncture and moxibustion group was higher than that in the model group(P<0.05).The levels of UHRF1 and DNMT1 mRNA and protein in the acupuncture and moxibustion group were insignificantly different from those in the normal endometrium(P>0.05). Conclusion:Acupuncture and moxibustion may up-regulate the levels of UHRF1 mRNA and UHRF1 and DNMT1 proteins in the ectopic endometrium to the normal level so as to reduce the volume of ectopic cysts and cure EMS in rats.

The pathogenesis of diabetic nephropathy(DN)is very complex.Ferroptosis as a kind of new way of cell death has become a research hotspot in recent years.It is widely known that DN is closely related to ferroptosis.Deactivation of system Xc--GSH-GPX4 axis,iron overload,lipid peroxidation and mitochondrial dysfunction play important role in occurrence and development of ferroptosis of DN,antioxidant protein may be a potential target for the treatment of ferroptosis of DN.Different pathways and interactions may alleviate the occurrence and development of ferroptosis by activating antioxidant protein such as GPX4,Nrf2,Sirtuin family protein and ferritin.Traditional Chinese medicine(TCM)has the characteristics of multi-component,multi-target and multi-pathway overall regulation.The active components and compounds of TCM have potential application value in improving renal injury and ferroptosis of DN by enhancing the expression of antioxidant protein,which provides a new research direction for delaying the progress of DN.

Objective:To explore the correlation between the early neurological deterioration and the poor short-term outcome after intravenous thrombolysis with recombinant tissue Plasmin activator (rt PA) in patients with acute ischemic stroke.Methods:A retrospective analysis of 268 patients with acute ischemic stroke who received recombinant tissue Plasmin activator(rt-PA) intravenous thrombolytic therapy in the Department of Neurology of Civil Aviation General Hospital from January 2019 to October 2022 was performed. The modified Rankin scale(mRS) was used to evaluate short-term outcome at 14 days after thrombolysis, with a score of 0 to 2 defined as good outcome and a score of 3 to 5 or death defined as poor outcome. Clinical, laboratory and imaging data of the two groups were collected. Univariate analysis was used to compare the baseline data of the two groups, and multivariate Logistic regression analysis was used to determine the independent risk factors for poor short-term outcomes.Results:Univariate analysis showed that age, baseline NIHSS score, fasting blood sugar, glycated hemoglobin, the proportion of coronary heart disease, proportion of atrial fibrillation, proportion of paraventricular high signal (3 score), proportion of hemorrhage transformation, proportion of END, proportion of double circulation infarction, proportion of new cortical infarction, proportion of new internal capsule infarction, proportion of large atherosclerosis of TOAST classification, and proportion of cardiogenic embolism of TOAST classification in the good outcome group were higher than those in the poor outcome group(68.00 (59.00, 80.00) years old vs 64.00 (54.50, 72.00) years old, 9 (6, 13) points vs 5 (3, 7) points, 6.85 (5.25, 9.20) mmol/L vs 5.64 (4.90, 6.75) mmol/L, 6.40 (5.70, 7.75)% vs 6.00 (5.60, 6.80)%, 31.3% (31/99) vs 17.7% (30/169), 28.3% (28/99) vs 9.5% (16/169), 26.3% (26/99) vs 13.0% (22/169), 19.2% (19/99) vs 5.9%(10/169), 53.5% (53/99) vs 21.9% (37/169), 10.1% (10/99) vs 2.4% (4/169), 44.4% (44/99) vs 22.5% (38/169), 41.4% (41/99) vs 27.8% (47/169), 33.3% (33/99) vs 17.8% (30/169), 25.3% (25/99) vs 6.5% (11/169)), the proportion of small artery occlusion and others of TOAST classification ,platelets were lower than the poor outcome group (29.3%(29/99) vs 53.8%(91/169),12.1%(12/99) vs 21.8%(37/169),199(163,240)×10 9/L vs 221(179,259)×10 9/L). The differences were statistically significant(the statistical values were U=2.80, U=7.94, U=3.24, U=2.29, χ 2=6.53, χ 2=16.11, χ 2=7.45, χ 2=11.40, χ 2=28.02, χ 2=7.54, χ 2=14.18, χ 2=5.24, χ 2=34.44, and U=2.16, respectively; P values were 0.005, <0.001, 0.001, 0.022, 0.011, <0.001, 0.006, 0.001, <0.001, 0.006, <0.001, 0.002, <0.001, and 0.031, respectively). Multivariate Logistic analysis showed that only baseline NIHSS score ( OR=1.212, 95% CI :1.123-1.309, P<0.001) and END ( OR=3.397, 95% CI:1.763-6.546, P<0.001) were independently related to the poor short-term outcome after intravenous thrombolysis in acute ischemic stroke patients. Conclusions:END and High baseline NIHSS score were independent risk factors for poor short-term outcome after intravenous thrombolysis in acute ischemic stroke patients.