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 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 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 predictive value of pulse pressure variation(PPV),stroke volume variation(SVV)and their changing values after tidal volume increase from 6 mL/kg to 8 mL/kg predicted body weight(PBW)on the volumetric responsiveness in the patients with acute respiratory distress syndrome(ARDS).Methods A prospective study was conducted.Twenty-three ARDS patients with acute circulatory failure treated in the intensive care unit(ICU)of this hospital from January 2021 to December 2022 were se-lected.The indicators such as PPV,SVV and cardiac index were recorded at the tidal volume of 6 mL/kg PBW,1 min after tidal volume challenge(tidal volume instantly increased to 8 mL/kg PBW),the tidal volume re-reduced to 6 mL/kg PBW,and after fluid bolus(FB),respectively.The cardiac index increase(ΔCI)≥15％served as the volumetric responsiveness positive when the tidal volume was re-reduced to 6 mL/kg PBW and after giving FB.The receiver operating characteristic(ROC)curve was used to evaluate the predictive value of PPV,SVV and their changing values for the volumetric responsiveness after the tidal volume increase from 6 mL/kg to 8 mL/kg PBW.Results A total of 42 measurements were performed in 23 patients.Among them,24 set of measurements were volumetric responsiveness positive(group R),and 18 set of measurements were volumetric responsiveness negative(group NR).The absolute values(ΔPPV6-8,ΔSVV6-8)and percentage(％ΔPPV6-8,％ΔSVV6-8)of PPV and SVV in tidal volume increase from 6 mL/kg to 8 mL/kg PBW had statisti-cal differences between the two groups(P＜0.05).ΔPPV6-8 and ΔSVV6-8 could predict the volumetric respon-siveness in the patients with ARDS.The area under the ROC curve(AUC)and its 95％CI were 0.92(0.84-1.00)and 0.90(0.81-0.99),and the optimal cut off values were 2.5％and 3.5％,respectively.When the tid-al volume was 6 mL/kg PBW,the PPV,SVV and central venous pressure(CVP)could not effectively predict the volumetric responsiveness in the patients with ARDS.Conclusion The efficiency of PPV or SVV changing values after tidal volume challenge for predicting the volumetric responsiveness of ARDS patients during low tidal volume ventilation is superior to PPV and SVV.

OBJECTIVE To evaluate the cost-effectiveness of ivabradine in the treatment of chronic heart failure （CHF） in the context of “Quadruple Therapy” from the perspective of the health system. METHODS Based on real-world cohort data， the Markov model was constructed according to the natural progression of CHF， with a cycle time of 3 months， a study timeframe of 20 years， and a discount rate of 5%. Using quality-adjusted life year （QALY） and incremental cost-effectiveness ratios （ICER） as the output indexes， the cost-utility analysis was used to evaluate the cost-effectiveness of ivabradine in combination with the “Quadruple Therapy” regimen， compared with the “Quadruple Therapy” regimen for the treatment of CHF， and the robustness of the results of the base analysis was verified by univariate sensitivity analysis and probabilistic sensitivity analysis. RESULTS The results of the base analysis showed that the ICER of ivabradine combined with the “Quadruple Therapy” regimen was 165 065.54 yuan/QALY， compared with the “Quadruple Therapy” regimen， which was lower than the willingness-to-pay （WTP） threshold （257 094 yuan/QALY） based on 3 times of China’s gross domestic product （GDP） per capita in 2022. The results of the univariate sensitivity analysis showed that the discount rate had the greatest impact on the robustness of the model. The probabilistic sensitivity analysis showed that the probability that the ivabradine combined with the “Quadruple Therapy” regimen was cost-effective under the WTP threshold in this study was 59.50%. CONCLUSIONS When using 3 times China’s 2022 GDP per capita （257 094 yuan/ QALY） as the WTP threshold， the combination of ivabradine and the “Quadruple Therapy” regimen for treating CHF is cost- effective.