To summarize Prof. ZHANG Zhiyuan's clinical experience in using large doses of Fuzi （Aconiti Lateralis Radix Praeparata）. The effect of Fuzi is based on its acrid and hot propoerties， warming and invigorating yang qi and running without guard. The application of large doses of Fuzi can be categorized into raw and processed， with common dosage ranging from 30 g to 60 g of raw Fuzi， and 15 g to 30 g， 30 g to 60 g of processed Fuzi. The quantity-effect relationship of the large dose of Fuzi is summarized as 15 g to 30 g of processed Fuzi could warm water， warm yang and eliminate timidity， as the treatment of asthma with deficiency cold phlegm， edema of yang deficiency， and panic and timidity of yang deficiency； 30 g to 60 g of processed Fuzi could tonify fire， warm the meridians and collaterals， assist yang to dispel cold and relieve pain， as the treatment of coldness in the limbs， abdominal pain， pain in the joints of the limbs， and loose stools due to deficient yang qi and exuberant internal yin cold； 30 g to 60 g raw Fuzi could restore yang to save from collapse， as the treatment of yang depletion after profuse sweating and vomiting. At the same time， different dosages of Fuzi were flexibly paired with other medicines， i.e.， 15 g to 30 g of processed Fuzi was paired with Mahuang （Ephedrae Herba） and Xixin （Asari Radix et Rhizoma） to assist yang to dispel coldness， 30 g to 60 g of processed Fuzi was paired with Baizhu （Atractylodis macrocephalae rhizoma） or Wuzhuyu （Euodiae Fructus） to warm yang and dispel dampness， and 30 g to 60 g of raw Fuzi was paired with Shanzhuyu （Corni Fructus） to tonify both yin and yang.

OBJECTIVE To provide references and recommendations for improving the regulatory framework for cell and gene therapy products and treatments in China. METHODS This study systematically examined the “dual-track regulatory” frameworks for regenerative medicine products and treatments in Japan and the Republic of Korea， summarized their beneficial experiences， and explored optimization strategies for China’s regulatory practices. RESULTS & CONCLUSIONS Both Japan and the Republic of Korea have established clear management processes for two distinct pathways “registered clinical trials for regenerative medicine products” and “clinical research on regenerative medicine treatments” guided by shared principles of “risk stratification” and “full lifecycle oversight”. Based on these findings， it is recommended that China： strengthen top-tier legislative framework to explicitly delineate the regulatory scope governing cell and gene therapy products and treatments； clarify the jurisdictional responsibilities of relevant regulatory bodies to enhance oversight efficacy； appropriately calibrate the regulatory scope， and adopt a balanced regulatory approach that harmonizes standardization with innovation incentives， thereby accelerating the clinical translation of regenerative medicine products.

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*

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

Objective:To explore the clinical effects of a 3D-printed intracranial pressure balancing device in preventing complications after suboccipital craniectomy (DC).Methods:This study is a retrospective cohort analysis. The clinical data of 35 patients who underwent DC at Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, from September 2020 to September 2023 were reviewed. The cohort included 24 males and 11 females, with an age of (48.7±14.9) years (range:17 to 74 years). Nineteen patients (experimental group) received the intracranial pressure balancing device fixed to the bone defect site post-DC. This device was made using medical-grade dicyanamide resin and was three dimensional printed based on postoperative CT scans of the patients. The remaining 16 patients (control group) did not receive the intracranial pressure balancing device, while other treatments and procedures were consistent with the experimental group. Data were compared using the χ2 test or Fisher′s exact probability method. Results:Out of the 35 patients, 30 cases (85.7%) experienced complications following DC. Specific complications included cerebral infarction in 3 cases (8.6%), intracerebral hemorrhage in 1 case (2.9%), subdural effusion in 27 cases (77.1%) with a median onset of (8.8±6.5) days (range: 1 to 23 days), brain tissue protrusion in 15 cases (42.9%) with a median onset of ( M(IQR)) 7.0 (21.0) days (range:2 to 106 days), and hydrocephalus in 6 cases (17.14%) with a median onset of 34.5 (111.0) days (range: 22 to 136 days). There were no significant differences in the occurrence of complications(all P>0.05). However, there was a significant reduction in the incidence of subdural effusion in the experimental group prior to cranioplasty ( P=0.013). No significant differences were noted in mRS scores between the two groups after cranioplasty ( P>0.05). Conclusions:The intracranial pressure balancing device has the effect of prevention and treatment of subdural effusion. However, it did not significantly improve patient prognosis post-DC, warranting further investigation.

Objective To explore the mortality rate and changes in splenic cell cycle and apoptosis in rats with ab-dominal infection.Methods An animal model of sepsis was induced by cecal ligation and puncture(CLP)in rats.At serial time points 0 h,6 h,12 h,24 h,48 h,and 72 h after CLP,the animal death rate was calculated.The percentage of cell cycle G1,S,G2/M phase and apoptosis of isolated spleen cells were analyzed using flow cytome-ter.The expression of p27 of spleen tissue was determined by Western blot analysis.Results In the rat model of CLP-induced systemic inflammatory response,the mortality of animals gradually increased at 0 h,6 h,12 h,24 h,48 h and 72 h after CLP surgery,reaching a maximum of 88.81%.The abdominal infection in the animals gradual-ly worsened at 0 h,6 h,12 h,and 24 h after CLP surgery,but localized and gradually alleviated after 48 h and 72 h.Within 48 h after CLP surgery,there was a blockage in the G1 phase of the spleen cell cycle,an increase in the percentage of apoptotic cells,and an elevation in p27 expression.After 48 h,the G1 phase blockage gradually recovered,the number of apoptotic cell decreased,and p27 expression declined.Additionally,with-in 48 h after CLP surgery,there was a decrease in the percentage of cells in the S and G2/M phases of the spleen cell cycle,but the percentage of cells in these phases gradually increased after 48 h.Conclusions Cell cycle arrest and apoptosis of the spleen cells are potentially contributed to the change of animal mortality after abdominal infection.

Objective To investigate the relationship between the expression of programmed death ligand 1(PD-L1)and hypoxia inducible factor-1α(HIF-1 α)with the clinical pathological characteristics and prognosis of gastric cancer patients.Methods The cancer tissues of 100 gastric cancer patients who underwent radical gastrectomy at the First Hospital of Handan City from July 2019 to July 2020 were selected as the research subjects,and their adjacent tissues(normal tissues ≥ 5 cm from the cancer tissues)were as the control group.Immunohistochemical detection of PD-L1 and HIF-1 α was performed by SP method.Spearman correlation analysis was used to analyze PD-L1 and HIF-1 α in gastric cancer tissues.Kaplan-Meier method was used to analyze the 3-year survival relationship of gastric cancer patients.The influencing factors of prognosis and death in patients with gastric cancer were analyzed by univariate and multivariate Cox regression.Results Among 100 gastric cancer patients,52 were PD-L1 positive and 48 were negative;67 were HIF-1 α positive and 33 were HIF-1 α negative,the positive expression rates of PD-L1 and HIF-1α in gastric cancer tissues were 52.00％and 67.00％,respectively,which were obviously higher than those in adjacent tissues(11.00％、18.00％),the difference was statistically significant(P＜0.05).Spearman correlation analysis showed that the expression of PD-L1 was positively correlated with that of HIF-1α in gastric cancer tissues(r=0.730,P＜0.001).The expressions of PD-L1 and HIF-1α in patients with gastric cancer were correlated with TNM stage,lymph node metastasis and local invasion(P＜0.05).The 3-year overall survival rate of gastric cancer patients was 48.00％after surgery,and the 3-years survival rate of patients with positive expression of PD-L1 and HIF-1α were 28.85％and 31.34％,which were lower than those of patients with negative expression of PD-L1 and HIF-1α(68.75％and 81.82％)(Log rank x2=25.155,P＜0.001.Log rank x2=24.552,P＜0.001).Moreover,positive expression of PD-L1 and HIF-1α,TNM staging of Ⅲ-Ⅳ,lymph node metastasis,and local infiltration were independent risk factors for prognosis and death in gastric cancer patients(P＜0.05).Conclusion Both PD-L1 and HIF-1α are highly expressed in cancer tissues of gastric cancer patients,and they are positively correlated.They are also associated with clinical pathological features such as TNM staging,lymph node metastasis,and poor prognosis.

Objective To evaluate the clinical use of the baseline CT angiography(CTA)quantitative score(self-designed collateral circulation quantitative,SD-CCQ)in determining the collateral circulation compensation status in patients with acute ischemic stroke(AIS),as well as the reliability and accuracy of the SD-CCQ score and the Alberta Stroke Program Early CT Score(ASPECTS).Methods Retrospective analysis was made on the clinical and imaging data,including CT,CTA and DWI image data,of 84 patients who were admitted for acute ischemic stroke to the Department of Neurorehabilitation of Zhongshan Hospital of Traditional Chinese Medicine from January 2020 to December 2022.Their CTA source images were annotated using a multi-task deep learning method for vascular segmentation.The ASPECTS score and SD-CCQ score were then applied to the CTA images following vascular segmentation in order to assess the collateral circulation compensation of AIS patients.The Kappa test was used to assess the consistency of the two methods used to assess collateral circulation,and the multifactorial Logistic regression analysis was used to examine the relationship between the SD-CCQ and the prognosis of the AIS patients.Results ASPECTS score had good consistency with SD-CCQ score in evaluating collateral circulation in AIS patients(κ=0.65,P＜0.001),and the diagnostic accuracy of the latter for benign collateral circulation in AIS was 96.15％.Logistic regression analysis showed that the new collateral circulation score,baseline NIHSS,and DWI infarct volume were the main factors affecting the long-term prognosis of AIS patients.Conclusion The new scoring system SD-CCQ can be used to evaluate the compensatory status of collateral circulation in AIS patients,which may help in clinical treatment decision-making and prognosis prediction.