Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of Panax notoginseng saponins (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS via profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated Lactobacilli in rats, and PNS markedly recovered Lactobacilli, particularly Lactobacillus reuteri (L.Reu). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the L.Reu colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing L.Reu proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by L.Reu in the pathogenesis and treatment of IS.

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

Stria vascularis（SV）, located in the lateral wall of the cochlea, is a highly vascularized tissue that plays a crucial role in maintaining the homeostasis of endolymph and normal auditory function, with its core function relying on the transporter system distributed within it. These transporters in the SV precisely mediate the transport of ions, nutrients, and metabolites, constituting the cornerstone of the homeostasis of endolymph. Abnormal expression or dysfunction of transporters in the SV can lead to an imbalance in the inner ear microenvironment, which can lead to hearing loss. However, the effects of transporters in SV on hearing loss have not been fully clarified. In this paper, the function and distribution of different types of transporters in SV and their relationship with hearing loss are reviewed, providing a new perspective and prospect for exploring the molecular basis of hearing loss and targeted therapies of transporters in the future.

[Objective]To summarize Professor ZHANG Guangji's thoughts and clinical experience in the treatment of senile insomnia based on the theory of"treating senile diseases from the perspective of Fu-organs".[Methods]By sorting out the discussions of previous medical scholars on the theory of"treating senile diseases from the perspective of Fu-organs"and Professor ZHANG's clinical interpretation,this paper,from three aspects,including the meaning of"treating senile diseases from the perspective of Fu-organs",the theoretical basis and specific application of treating senile insomnia from the perspective of Fu-organs,combining with typical medical records observed in the clinic,explores the feasibility and practical ideas of treating senile insomnia from the perspective of Fu-organs.[Results]Professor ZHANG believes that the meaning of Fu-organs includes not only the six hollow organs but also the source of engendering transformation,as well as the blood vessels and Xuanfu(sweat pore).The theoretical basis for treating senile insomnia by"seeking treatment from the Fu-organs"lies in the fact that the smoothness of the Fu-organs is of great significance for the sleep health of the elderly,and the obstruction of the Fu-organs plays an important role in the occurrence of senile insomnia.Specifically,the obstruction of the stomach,blood vessels and sweat pore impedes the pathway where Yin and Yang converge,resulting in their inability to interact.This disruption affects both the onset and maintenance of sleep.Therefore,in treatment,it is essential to focus on maintaining the smooth circulation of the gastrointestinal tract,blood vessels and sweat pore,enabling the free flow of Yin and Yang.A medical case was presented here.An elderly patient with insomnia was diagnosed with the syndromes of liver Qi stagnation transforming into fire,blood stasis obstructing the collaterals,stomach Qi disharmony and obstruction of the Xuanfu(minute orifices).By adopting the treatment principles of soothing the liver and regulating the stomach,promoting blood circulation to remove stasis and opening the Xuanfu,and calming the mind,good therapeutic effects were achieved.Specifically,Zhishi Xiaopi Pills were used to smooth the Qi circulation in the stomach-related Fu-organs,Xuefu Zhuyu Decoction was employed to promote blood circulation in the blood-related Fu-organs,and Danzhi Xiaoyao Powder combined with acupuncture was utilized to open the Xuanfu.[Conclusion]The theory of"treating senile diseases from the perspective of Fu-organs"is feasible,and Professor ZHANG Guangji's clinical experience is unique,providing a certain perspective for the prevention and treatment of senile insomnia.

[Objective]To explain the essence and connotation of micro syndrome differentiation,using"blood stasis"as a medium,providing an academic reference for the future development of clinical differentiation systems.[Methods]It deepens the understanding of the theoretical system and thinking mode of microcosmic syndrome differentiation by analyzing the theory of"microcosmic syndrome differentiation"and clinical aspects.Using"blood stasis"as an example,the paper establishes the connection between macroscopic and microcosmic syndrome differentiation.It also proposes methods and approaches for exploring microcosmic syndrome differentiation,supported by clinical experience.[Results]Microcosmic syndrome differentiation,through the application of modern detection technologies,has achieved an extension from"external Xiang"to"internal Xiang",transforming abstract pathomechanisms such as"rough pulse"in traditional macroscopic syndrome differentiation into quantifiable microscopic blood indicators.This effectively compensates for the limitations of macroscopic syndrome differentiation in delayed information acquisition and subjective interpretation.Employing a research approach of"exploring Xiang through theory-inferring Xiang from changes-validating Xiang with prescriptions and syndromes",not only has an intrinsic connection among microscopic indicators like hemorheology,and traditional syndrome differentiation has been confirmed,but the clinical value of microcosmic syndrome differentiation has also been corroborated through the efficacy of blood-activating and stasis-resolving drugs.[Conclusion]Microcosmic syndrome differentiation,through the organic integration of modern technology and traditional theory,not only broadens the dimensions of syndrome differentiation but also promotes the development of traditional Chinese medicine diagnosis and treatment towards greater objectivity and precision,which offers a promising pathway for the modernization of traditional Chinese medicine.

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

[Objective]To explain the essence and connotation of micro syndrome differentiation,using"blood stasis"as a medium,providing an academic reference for the future development of clinical differentiation systems.[Methods]It deepens the understanding of the theoretical system and thinking mode of microcosmic syndrome differentiation by analyzing the theory of"microcosmic syndrome differentiation"and clinical aspects.Using"blood stasis"as an example,the paper establishes the connection between macroscopic and microcosmic syndrome differentiation.It also proposes methods and approaches for exploring microcosmic syndrome differentiation,supported by clinical experience.[Results]Microcosmic syndrome differentiation,through the application of modern detection technologies,has achieved an extension from"external Xiang"to"internal Xiang",transforming abstract pathomechanisms such as"rough pulse"in traditional macroscopic syndrome differentiation into quantifiable microscopic blood indicators.This effectively compensates for the limitations of macroscopic syndrome differentiation in delayed information acquisition and subjective interpretation.Employing a research approach of"exploring Xiang through theory-inferring Xiang from changes-validating Xiang with prescriptions and syndromes",not only has an intrinsic connection among microscopic indicators like hemorheology,and traditional syndrome differentiation has been confirmed,but the clinical value of microcosmic syndrome differentiation has also been corroborated through the efficacy of blood-activating and stasis-resolving drugs.[Conclusion]Microcosmic syndrome differentiation,through the organic integration of modern technology and traditional theory,not only broadens the dimensions of syndrome differentiation but also promotes the development of traditional Chinese medicine diagnosis and treatment towards greater objectivity and precision,which offers a promising pathway for the modernization of traditional Chinese medicine.

[Objective]To summarize Professor ZHANG Guangji's thoughts and clinical experience in the treatment of senile insomnia based on the theory of"treating senile diseases from the perspective of Fu-organs".[Methods]By sorting out the discussions of previous medical scholars on the theory of"treating senile diseases from the perspective of Fu-organs"and Professor ZHANG's clinical interpretation,this paper,from three aspects,including the meaning of"treating senile diseases from the perspective of Fu-organs",the theoretical basis and specific application of treating senile insomnia from the perspective of Fu-organs,combining with typical medical records observed in the clinic,explores the feasibility and practical ideas of treating senile insomnia from the perspective of Fu-organs.[Results]Professor ZHANG believes that the meaning of Fu-organs includes not only the six hollow organs but also the source of engendering transformation,as well as the blood vessels and Xuanfu(sweat pore).The theoretical basis for treating senile insomnia by"seeking treatment from the Fu-organs"lies in the fact that the smoothness of the Fu-organs is of great significance for the sleep health of the elderly,and the obstruction of the Fu-organs plays an important role in the occurrence of senile insomnia.Specifically,the obstruction of the stomach,blood vessels and sweat pore impedes the pathway where Yin and Yang converge,resulting in their inability to interact.This disruption affects both the onset and maintenance of sleep.Therefore,in treatment,it is essential to focus on maintaining the smooth circulation of the gastrointestinal tract,blood vessels and sweat pore,enabling the free flow of Yin and Yang.A medical case was presented here.An elderly patient with insomnia was diagnosed with the syndromes of liver Qi stagnation transforming into fire,blood stasis obstructing the collaterals,stomach Qi disharmony and obstruction of the Xuanfu(minute orifices).By adopting the treatment principles of soothing the liver and regulating the stomach,promoting blood circulation to remove stasis and opening the Xuanfu,and calming the mind,good therapeutic effects were achieved.Specifically,Zhishi Xiaopi Pills were used to smooth the Qi circulation in the stomach-related Fu-organs,Xuefu Zhuyu Decoction was employed to promote blood circulation in the blood-related Fu-organs,and Danzhi Xiaoyao Powder combined with acupuncture was utilized to open the Xuanfu.[Conclusion]The theory of"treating senile diseases from the perspective of Fu-organs"is feasible,and Professor ZHANG Guangji's clinical experience is unique,providing a certain perspective for the prevention and treatment of senile insomnia.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.