In response to the clinical needs of cancer treatment and rehabilitation, Professor Lin Hongsheng proposed the Wuzhi Wuyang (five treatments and rehabilitation) concept on the basis of years of clinical experience and the Guben Qingyuan (consolidate the foundation and clear the source) theory. Wuzhi Wuyang emphasizes the importance of treatment and rehabilitation and aims to provide personalized and stage-specific treatment and rehabilitation plans by integrating the advantages of traditional Chinese medicine (TCM) and modern medicine to achieve comprehensive life-cycle management for patients with cancer. The proposal of Wuzhi Wuyang has provided new ideas and methods for the treatment, prevention, and rehabilitation of cancer, along with valuable references for clinical practice and academic research. This article summarizes the connotation of Wuzhi Wuyang and its application in the comprehensive management of cancer prevention and treatment with TCM.

OBJECTIVE To provide direction and reference for the adjustment of the discount rate （DR） in China’s pharmacoeconomic guidelines. METHODS Search was conducted on the official websites of the International Society for Pharmacoeconomics and Outcomes Research， health technology assessment agencies in various countries/regions， as well as relevant websites of other upper-middle-income or high-income countries/regions. The recommended DR， adjustment trends， and setting rationales in pharmacoeconomic evaluation guidelines across different countries/regions were then summarized and compared. Based on theoretical derivation and literature analysis， the effects of different DR on the incremental cost-effectiveness ratio （ICER） were examined. RESULTS & CONCLUSIONS Among the 40 included guidelines， the base-case DR ranged from 1.5% to 5%， with 5% being the most common value； the range for sensitivity analysis was 0 to 12%. Thirty-six countries/regions applied the same DR to both costs and health outcomes， while in the Netherlands， Belgium， Poland and Czech Republic， DR for costs was higher than for health outcomes. In recent years， Korea， France and Ireland had lowered their DR in response to economic changes， whereas the Netherlands and Czech Republic had raised their DR for cost. The setting of the DR was primarily based on the public project investment interest rate or referred to recommendations from internationally authoritative institutions and other relevant guidelines. The direction and magnitude of the impact of different DR on the ICER largely depended on the distribution of costs and health outcomes between the intervention and reference measure. The setting and adjustment of DR were closely associated with the economic environment. Based on international experience, the DR in China can be lowered by 0.5% to 1.5%， and localized empirical research can be conducted using internationally common estimation methods.

Objective:To investigate the value of soluble interleukin-6 (IL-6) receptor (sIL-6R) level in predicting ultrafiltration insufficiency in peritoneal dialysis (PD) patients.Methods:It was a prospective cohort study. The patients who received continuous ambulatory PD and regular follow-up between November 2016 and July 2018 in the PD Center of Renji Hospital, School of Medicine, Shanghai Jiao Tong University were enrolled. Enzyme-linked immunosorbent assay was used to determine dialysate sIL-6R and its appearance rate (AR) was calculated. Patients were divided into high sIL-6R AR group and low sIL-6R AR group according to median value of sIL-6R AR and prospectively followed up until death, PD cessation, or the end of the study (December 31, 2022). Multiple linear regression was used to analyze the related factors of sIL-6R AR. Kaplan-Meier method and log-rank test were used to compare the survival rate difference of ultrafiltration insufficiency between high sIL-6R AR group and low sIL-6R AR group. Multivariate Cox regression and multivariate competing risk models were used to assess the risk factors associated with occurrence of ultrafiltration insufficiency.Results:A total of 198 PD patients were enrolled, including 115 (58.1%) males, with age of (54.9±13.7) years old and PD duration of 22.5 (6.6, 65.0) months. The sIL-6R AR of the cohort was 2 094.7 (1 672.4, 2 920.9) pg/min. Compared with low sIL-6R AR（<2 094.7 pg/min）group, high sIL-6R AR（>2 094.7 pg/min）group had older age ( t=-3.269, P=0.001), higher body mass index ( t=-3.248, P=0.001), proportion of combined diabetes mellitus ( χ2=8.890, P=0.003), 24 h glucose exposure ( Z=-2.257, P=0.024), 24 h ultrafiltration capacity ( Z=-2.515, P=0.012), 4 h dialysate creatinine to serum creatinine ratio ( t=-2.609, P=0.010), mass transfer area coefficient of creatinine ( Z=-2.308, P=0.021), IL-6 AR ( Z=-3.533, P<0.001) and solute glycoprotein 130 AR ( Z=-8.670, P<0.001), and lower serum albumin ( t=2.595, P=0.010) and residual renal function ( t=2.133, P=0.033). Multiple linear regression analysis showed that body mass index ( β=0.194, P=0.005), serum albumin ( β=-0.215, P=0.002) and dialysate lg[IL-6 AR] ( β=0.197, P=0.011) were independently correlated with sIL-6R AR. By the end of the study, 57 (28.8%) patients developed ultrafiltration insufficiency. Kaplan-Meier analysis showed that high sIL-6R AR group had a significantly inferior ultrafiltration insufficiency-free survival rate than that in low sIL-6R AR group (log-rank χ 2=5.375, P=0.020). Multivariate Cox regression analysis and multivariate competing risk models showed that high dialysate sIL-6R AR (>2 094.7 pg/min) was an independent influencing factor of ultrafiltration insufficiency ( HR=2.286 , 95% CI 1.254-4.165 , P=0.007 ; SHR=2.074, 95% CI 1.124-3.828, P=0.020) in PD patients. Conclusions:Dialysate sIL-6R level was associated with body mass index, serum albumin and dialysate IL-6 level. Dialysate sIL-6R may be a predictive factor of ultrafiltration insufficiency in PD patients.

Objective:To explore the clinical warning value of ischemic modified albumin (IMA) and IMA to human serum albumin (HSA) ratio (IMAR) in the development of pre-eclampsia (PE) and its severity.Methods:A total of 156 pregnant women with PE admitted to the Haidian District Maternal and Child Health Hospital of Beijing from April 2022 to March 2023 were collected as the PE group, and 156 healthy pregnant women with the same age and gestational age were matched as the control group. PE pregnant women were further divided into severe PE group (78 cases) and non-severe PE group (78 cases). Severe PE pregnant women were divided into emergency group (42 cases) and non-emergency group (36 cases) according to the disease progression time.All pregnant women were stratified according to their HSA levels (<30 g/L, 30-32 g/L, ≥32 g/L), and the peripheral blood IMA, HSA, and IMAR of pregnant women in different periods and subgroups were compared, and also the difference of IMA levels in umbilical artery blood. Bivariate correlation analysis was used to explore the correlation between severe PE and IMA or IMAR, and receiver operating characteristic (ROC) curves was used to analyze the diagnostic value of IMA, HSA, and IMAR for PE and severe PE.Results:(1) The IMA level and IMAR in peripheral serum of pregnant women in the PE group at diagnosis, and the IMA level in umbilical artery blood at delivery, and peripheral serum at 2 days after delivery were higher than those in the control group. The HSA level in peripheral serum was lower than that in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (2) The IMA level and IMAR in the peripheral serum of pregnant women with severe PE were higher than those in the non-severe PE group at diagnosis, while the HSA level were lower than those in the non-severe PE group. The differences were statistically significant (all P<0.05). At diagnosis, the IMA level and IMAR in peripheral serum of pregnant women in the emergency group were higher than those in the non-emergency group, while the HSA level was lower than that in the non-emergency group. The differences were statistically significant (all P<0.05). When diagnosed, the peripheral serum IMA levels of pregnant women in the PE group were compared between subgroups with HSA<30 g/L, 30-32 g/L, ≥32 g/L, and there was no statistically significant difference ( F=0.366, P=0.694). However, the IMAR was compared between the three subgroups, and the difference was statistically significant ( F=28.544, P<0.001), which increased with the decrease of HSA levels. In the subgroup with HSA≥32 g/L, the peripheral serum IMA level and IMAR of pregnant women in the PE group were higher than those in the control group at diagnosis, and the differences were statistically significant (all P<0.001). (3) The severe PE manifestations positively correlated with peripheral serum IMAR at diagnosis include systolic blood pressure ( r=0.279), mean arterial pressure ( r=0.212), and urinary protein quantification ( r=0.277), while the severe PE manifestations negatively correlated include HSA levels ( r=-0.644) and newborn birth weight ( r=-0.305), all of which were significantly correlated ( P<0.05). (4) The area under curve (AUC) for IMAR diagnosis of PE was 0.875 (95% CI: 0.833-0.916), with the highest diagnostic efficiency at a cutoff value of 2.06, sensitivity of 72.5%, and specificity of 85.1%. The AUC for diagnosing severe PE was 0.871 (95% CI: 0.822-0.919), with the highest diagnostic efficacy at a cutoff value of 2.18, sensitivity of 72.3%, and specificity of 88.3%. The diagnostic efficacy of IMAR for PE and severe PE were higher than those of IMA and HSA levels. Conclusions:The level of IMA and IMAR in pregnant women with PE are higher than those in normal pregnant women. IMA and IMAR are correlated with the severity of PE, with IMAR changes occurring earlier and more significantly. IMAR could be considered as one of the evaluation indicators for the development of PE, or as a more sensitive PE severity warning indicator than HSA.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION chictr.org.cn, ChiCTR 2100043775.
Humans ; Fluorouracil/therapeutic use* ; Leucovorin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Proportional Hazards Models ; Prognosis

Objective:To explore the value of 18F-FDG PET/CT radiomics in predicting the cervical lymph node metastasis in salivary gland cancer. Methods:Sixty-eight patients with salivary gland carcinoma treated in the Peking University School and Hospital of Stomatology were retrospectively studied. They were randomly divided into training group ( n=40), validation group ( n=14), and test group ( n=14). The primary tumor lesions were semi-automatically delineated on PET images as regions of interest (ROIs) and the radiomic features were extracted from ROIs. After feature selection and dimension reduction, an artificial neural network (ANN) prediction model was constructed. The prediction performance of the model was assessed using receiver operating characteristic (ROC) curves, the area under ROC curves (AUC), accuracy, sensitivity, and specificity. Moreover, the performance of various models was compared using the Delong test. Results:The radiomic model yielded an AUC of 0.88 (95% CI: 0.78-0.95), a sensitivity of 75%, specificity of 92.3%, and accuracy of 88.2%. By contrast, the combined model constructed based on the clinical node status (cN) reported by PET/CT and radiomic features yielded an AUC of 0.97 (95% CI: 0.89-0.99), a sensitivity of 87.5%, specificity of 100%, and accuracy of 97.1%. The Delong test showed that there was a statistically significant difference between the combined model and cN ( Z=2.27, P<0.05), but there was no statistically significant difference between the radiomic model and cN ( P>0.05). Conclusions:The ANN model based on 18F-FDG PET/CT radiomics combined with cN reported by PET/CT can more accurately predict cervical lymph node metastasis in patients with salivary gland carcinoma.

Objective:To evaluate the identification rate of separating gel or HB&L pretreatment methods of MALDI-TOF-MS, thereby to provide a new idea for the rapid and accurate identification of pathogens of bloodstream infections in daily clinic practice.Methods:A total of 149 alarmed positive blood culture samples of single bacterial infection by routine laboratory methods were collected between January to December 2020 from the Sixth Medical Center, Chinese PLA General Hospital. Samples were pretreated with the separation gel accelerating tube method or the HB&L microbial culture system, followed by direct MALDI-TOF MS bacterial identification, the identification rates of the two pretreatment methods were compared and results from the traditional method were used as the standard control.Results:Among the 149 positive blood culture samples, 47.0% (70/149) were gram-negative (G -) bacteria and 53.0% (79/149) were gram-positive (G +) bacteria. Identification rate of G -strain level was 78.6% (55/70) by serum separation gel coagulation tube method and 91.4% (64/70) by HB&L microbial culture system, the difference was statistically significant ( P=0.033). Identification rate of G +strain levels was 73.4% (58/79) by serum separation gel coagulation tube method and 87.3% (69/79) by HB&L microbial culture system, the difference was statistically significant ( P=0.028). For G -bacteria in the range of 3.000-2.300, the identification rate was 22.9% (16/70) by serum separation gel accelerating tube method and 38.6% (27/70) by the HB&L microbial culture system, the difference was statistically significant ( P=0.044). For G +bacteria in the range of 3.000-2.300, the identification rate was 19.0% (15/79) by serum separation gel accelerating tube method and 34.2% (27/79) by the HB&L microbial culture system, the difference was statistically significant ( P=0.031). Conclusion:The identification rate of HB&L microbial culture system is higher than that of serum separation gel coagulation tube method. Direct MALDI-TOF MS identification of pathogenic bacteria in positive blood culture samples after pretreatment is feasible in daily clinical practice.

Objective: To study the response characteristics of the posterior intralaminar nucleus (PIN) of auditory thalamus in VGluT2-Cre transgenic adult mice when exposed to white noise and 10K pure tone stimulation. Methods: All adult male Vglut2-Cre mice (8-12 weeks) were used in this study between Oct, 2017 and Oct, 2018. Using the calcium signal fiber photometry method, optic fiber was employed to locate on PIN by injecting AAV-hSyn-DIO-GCaMP6m virus, and thereafter, the activity of the target cluster neurons during different acoustic stimuli was recorded. Matlab was used for data processing and statistical analysis. Results: (1)In both white noise and 10 kHz pure tone as a continuous three-second stimulation, the peak amplitude of calcium signal activity generated in PIN by white noise was superior to that of pure tone, the statistic result showed significantly difference (n=6, t=2.404, P=0.037 1) . (2)In addition, when white noise and 10K pure tone played as consecutive 3 or 5 pips within three-second stimulation, the stimulus-following ability in a consecutive 3 pulses play within 3 seconds was far better than a consecutive 5 pips play within 3 seconds (in both white noise and 10 kHz pure tone), yet consecutive 3 pips play showed greater signal attenuation speed than that in consecutive 5 pips play, the statistic result showed significantly difference (n=6, t=2.748 P=0.033 4) .(3)Regardless of the intra-group comparisons between white noise and 10 kHz pure tone stimulation, PIN showed better signal response in a consecutive 3 pips play than consecutive 5 pips play or a continuous three-second stimulation. When came to the statistical analysis, the acoustic response degree of a continuous three-second stimulation was an intermediate between two others, both consecutive 3 or 5 pips play showed significantly difference. Conclusions The results suggest that under the same acoustic intensity, VGluT2-Cre transgenic adult mice′s PIN shows greater signal response in white noise than pure tone. PIN shows greater signal attenuation to repetition play of 10 kHz pure tone, which implies PIN shows stronger adaptation to 10 kHz pure tone than to white noise. Lastly, PIN is more responsive to a complex sound information (white noise) than to simple sound information (pure tone).

Objective To evaluate the effectiveness of quantitative midbrain measurements in differentiating progressive supranuclear palsy (PSP) from multiple system atrophy (MSA) and Parkinson's disease (PD).Methods Quantitative midbrain measurements,including midbrain width (MW),midbrain to pons ratio (M/P) and magnetic resonance parkinsonism index (MRPI),were performed in patients with parkinsonism who were diagnosed in the Movement Disorder Clinic of Peking Union Medical College Hospital during the period of January to September 2017.A cross-sectional study was conducted in the series to evaluate the effectiveness of these quantitative measurements.Results Ten PSP-RS,15 MSA-P and 49 PD patients were included in this study.The values of MW,M/P and MRPI in PSP-RS patients were (8.21 ± 1.30) mm,0.49 ±0.06 and 15.26 ±4.53,respectively,with statistically significant difference compared toMSA-P ((10.24±0.77) mm,0.65 ±0.09,7.75 ±2.71) and PD patients ((10.53 ±0.93) mm,0.62±0.06,9.86 ±2.46;F=24.27,18.37,21.47,all P＜0.01).After adjusting for age,disease course and gender,analysis of covariance suggested significant correlation between the quantitative midbrain measurements and diagnosis of these diseases.Receiver operating characteristic curve indicated that MW ≤9.4 mm,M/P≤0.57 and MRPI ＞ 10.77 showed ideal sensitivity and specificity (90.0％ and 92.1％,80.0％ and 93.7％,100.0％ and 82.5％) in differentiating PSP-RS from MSA-P and PD.Conclusion Quantitative measurement of midbrain atrophy is useful in differentiating PSP-RS from MSA-P and PD.