As a pharmaceutical excipient with low caloric value, low hygroscopicity, and high stability, mannitol is widely used in various dosage forms, such as solid, lyophilized and inhalation preparations, etc. It has different crystal structures (α, β and δ) and cocrystal, and the changes in the crystal structure will affect formulation properties of pharmaceutical formulations. This paper reviews structural features, physicochemical properties, and preparation methods of mannitol polymorphs and cocrystal formation, with emphasis on polymorphic transformation pathways, monitoring methods and the effect of polymorphic transformation on properties and application in pharmaceutical formulations, including tabletability, disintegration and dissolution properties. By systematically summarizing the crystallographic study of mannitol, this study attempts to provide new ideas for the development of novel pharmaceutical excipients and applications in pharmaceutical formulations.

As a pharmaceutical excipient with low caloric value, low hygroscopicity, and high stability, mannitol is widely used in various dosage forms, such as solid, lyophilized and inhalation preparations, etc. It has different crystal structures (α, β and δ) and cocrystal, and the changes in the crystal structure will affect formulation properties of pharmaceutical formulations. This paper reviews structural features, physicochemical properties, and preparation methods of mannitol polymorphs and cocrystal formation, with emphasis on polymorphic transformation pathways, monitoring methods and the effect of polymorphic transformation on properties and application in pharmaceutical formulations, including tabletability, disintegration and dissolution properties. By systematically summarizing the crystallographic study of mannitol, this study attempts to provide new ideas for the development of novel pharmaceutical excipients and applications in pharmaceutical formulations.

ObjectiveTo establish and validate a new prediction model for the risk of death in patients with acute-on-chronic liver failure （ACLF） based on sarcopenia and other clinical indicators， and to improve the accuracy of prognostic assessment for ACLF patients. MethodsA total of 380 patients with ACLF who were admitted to Beijing YouAn Hospital， Capital Medical University， from January 2019 to January 2022 were enrolled， and they were divided into training group with 228 patients and testing group with 152 patients in a ratio of 6∶4 using the stratified random sampling method. For the training group， CT images were used to measure the cross-sectional area of the skeletal muscle at the third lumbar vertebra （L3）， and L3 skeletal muscle index （L3-SMI） was calculated. Sarcopenia was diagnosed based on the previously established L3-SMI reference values for healthy adults in northern China. Univariate and multivariable Cox regression analyses were used to establish a sarcopenia-ACLF model which integrated sarcopenia and clinical risk factors， and a nomogram was developed for presentation. The area under the ROC curve （AUC） was used to assess the predictive performance of the model， the calibration curve was used to assess the degree of calibration， and a decision curve analysis was used to investigate the clinical application value of the model. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison between groups. The DeLong test was used for comparison of AUC between different models. ResultsThe multivariate Cox regression analysis showed that sarcopenia （hazard ratio ［HR］=1.962， 95% confidence interval ［CI］： 1.185‍ ‍—‍ ‍3.250， P=0.009）， total bilirubin （HR=1.003， 95%CI： 1.002‍ ‍—‍ ‍1.005， P<0.001）， international normalized ratio （HR=1.997， 95%CI： 1.674‍ ‍—‍ ‍2.382， P<0.001）， and lactic acid （HR=1.382， 95%CI： 1.170‍ ‍—‍ ‍1.632， P<0.001） were included in the sarcopenia-ACLF model. In the training cohort， the sarcopenia-ACLF model had a larger AUC than MELD-Na score in predicting 90-day mortality in patients with ACLF （0.80 vs 0.73， Z=1.97， P=0.049）. In the test cohort， the sarcopenia-ACLF model had a significantly larger AUC than MELD score （0.79 vs 0.69， Z=2.70， P=0.007） and MELD-Na score （0.79 vs 0.68， Z=2.92， P=0.004）. The calibration curve showed that the model had good calibration ability， with a relatively good consistency between the predicted risk of mortality and the observed results. The DCA results showed that within a reasonable range of threshold probabilities， the sarcopenia-ACLF model showed a greater net benefit than MELD and MELD-Na scores in both the training cohort and the test cohort. ConclusionThe sarcopenia-ACLF model developed in this study provides a more accurate tool for predicting the risk of 90-day mortality in ACLF patients， which provides support for clinical decision-making and helps to optimize treatment strategies.

Objective To systematically evaluate the efficacy of Xixian Tongshuan Capsules/Pills in the treatment of acute ischemic stroke(AIS).Methods Literature about Xixian Tongshuan Preparation combined with conventional Western medicine for the treatment of AIS was retrieved from CNKI,SinoMed,VIP,Wanfang Data,PubMed,Medline,Embase,Cochrane Library and Web of Science from establishment of the databases to February 28,2023.Meta-analysis was conducted for the studies that could be quantitatively analyzed.The effective rate and response indicators were combined.Results A total of 7 articles were included for Meta-analysis.Results showed that there was statistical difference in the effective rate(RR=0.34,95%CI[0.23,0.51],P<0.01),NIHSS score(MD=-2.90,95%CI[-3.74,-2.06],P<0.01),BI score(MD=-10.08,95%CI[-13.47,-6.68],P<0.01),FIB(MD=-1.18,95%CI[-1.59,-0.77],P<0.01)of Xixian Tongshuan Preparation combined with conventional Western medicine for the treatment of AIS.There was no statistical difference in IL-6(MD=-15.4,95%CI[-33.3,2.49],P=0.09).There was no statistical difference in the effects of different dosage forms and treatment courses on the effective rate and NIHSS score.Conclusion The combination of Xixian Tongshuan Capsules/Pills could better improve the NIHSS and BI scores of patients with AIS,recovery the neurological function,and reduce the risk of blood hypercoagulability by reducing FIB content,with good safety.

Objective To investigate the correlation between lipid-related index and diabetic kidney disease(DKD)by observing the expression levels of lipid-related index in different stages of DKD.Methods A total of 265 patients with type 2 diabetes mellitus(T2DM)were divided into the T2DM group(n=106)and the DKD group(n=159).According to estimated glomerular filtration rate(eGFR)level,the DKD group was sub-divided into the DKD-G2 group(n=59),the DKD-G3 group(n=59)and the DKD-G4 group(n=41).Data of triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein A(Apo A),Apo B and urinary albumin/urinary creatinine ratio(UACR)were collected.Gomerular filtration rate(eGFR),triglyceride-glucose index(TyG),visceral adiposity index(VAI)and atherogenic index of plasma(AIP)were calculated.The differences of TyG,VAI and AIP between different groups and their correlation with eGFR and UACR were analyzed.Multiple linear regression analysis of DKD renal injury factors was conducted.Receiver operating characteristic(ROC)curves were drawn to evaluate the predictive efficiency of TyG,VAI,and AIP.Results The levels of TyG,VAI and AIP were significantly higher in the DKD group compared to the T2DM group,and these indices exhibited an increasing trend with disease progression(P＜0.05).Furthermore,there was a negative correlation between TyG,VAI,AIP and eGFR(r=-0.396,-0.425,-0.519,P＜0.01),and a positive correlation between UACR and eGFR(r=0.482,0.479 and 0.583,P＜0.01)in DKD patients.Multiple linear regression results showed that VAI and AIP were independent risk factors for eGFR,and TG,HDL-C,LDL-C,Apo B and VAI were influencing factors of UACR(P＜0.05).The ROC curve analysis revealed that the areas under the curves for TyG,VAI and AIP were 0.902(0.866-0.937),0.969(0.953-0.986)and 0.958(0.937-0.979)respectively.Conclusion The levels of TyG,VAI and AIP are correlated with the progression of DKD,and have predictive value for the occurrence and development of DKD.These biomarkers can be used as a biological indicator to evaluate the occurrence and development of DKD.

This article reviews the demand, development process, aid types, effects, and existing problems of decision aids for colorectal cancer. The aim is to provide reference for the development of convenient and efficient decision aids for colorectal cancer diagnosis and treatment in China, and to improve the quality of treatment decisions for colorectal cancer patients.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.

In the design of randomized controlled trials （RCT）， difficulties in patient recruitment and enrollment of control group would limit the overall implementation of the trials. In recent years， as a data source， real-world data （RWD） plays an increasingly important role in the medical field. In RCT of Chinese medicine， RWD could be designed as control group. This design can effectively solve the problem of inclusion difficulty for the patients in the western medicine control group of traditional Chinese medicine（TCM） RCT， it also can provide high quality evidence to evaluate the efficacy of TCM. In recent years， propensity score method has been widely used to deal with confounding factors in real world study. In this paper， four common research designs based on propensity score method were introduced with examples， including propensity score matching and data augmentation， two-stage design of propensity score stratification method， propensity score-integrated composite likelihood approach， and combination of different propensity score methods. However， there are some methodological challenges in this type of design， including the RWD data sources must be of high quality and the key information needs to be collected in a standardized method， the baseline characteristics of RCT and RWD patients should be comparable， and all known covariates related to the intervention and outcome need to be included for analysis. When adopting this design in the field of TCM， there are still some problems such as the lack of TCM syndrome information and TCM outcomes in RWD. When using RWD， it is necessary to decide how to analyze according to the data condition. This paper discussed the design types and methodological challenges of using RWD as control group in RCT， hoping to provide methodological ideas for researchers to use this type of design in the future.

Objective: To learn about the characteristics of physical activity(PA) and physical fitness, and to provide basis for the health and development of the Tibetan students. Methods: The cluster stratified random sampling was used, and 8 945 Tibetan students in Tibet were selected in May to June, 2019, and were administrated with questionnaire. Independent samples t test, one way ANOVA and Pearson correlation analysis were used. Results: There were significant differences of PA, and physical fitness by gender, grade and living area among Tibetan adolescents ( P <0.05). The PA score of boys(2.79±0.58) was higher than that of girls( 2.51 ±0.56), while the physical fitness level of girls(62.40±25.55) was higher than that of boys(59.26±26.55). The PA score( 2.59 ±0.55) of rural Tibetan children and youth was lower than those of urban areas, while the physical fitness level(61.53±26.53) was only lower than that of county area; the PA score(2.60±0.58) of Tibetan children and youth was the lowest for grade 7 and 9, while physical fitness level(57.62±24.33) was the lowest for grade 5 and 6. PA was not significantly correlated with physical fitness of Tibetan adolescents( r =-0.01， P >0.05). Conclusion Lack of physical activity and poor physical fitness are observed in Tibetan adolescents. It is suggested that schools, families and society should cooperate in various aspects and actively take measures to improve the physical health level of Tibetan children and adolescents.

Objective:To investigate the high-risk factors affecting the prognosis of patients with pT 1-2N 1M 0 after mastectomy, establish a nomogram prediction model, perform risk stratification, and screen the radiotherapy benefit populations. Methods:Clinical data of 936 patients with pT 1-2N 1M 0 breast cancer undergoing mastectomy in the Fourth Hospital of Hebei Medical University from January 2010 to December 2016 were retrospectively analyzed and 908 cases had complete follow-up data. They were divided into the radiotherapy (RT) group ( n=583) and non radiotherapy (NRT) group ( n=325) according to the radiotherapy. After propensity score matching (PSM) was performed 1 vs. 1, 298 cases were assigned into the RT group and 298 in the NRT group. Overall survival (OS) and disease-free survival (DFS) were compared between two groups using log-rank test. Nomogram prediction model was established, the survival differences were compared among different risk groups, and the radiotherapy benefit populations were screened. Results:Univariate analysis showed that the 5- and 8-year OS and DFS in the RT group were significantly better than those in the NRT group (both P<0.001). Multivariate analysis showed that age, tumor quadrant, number of lymph node metastases, T staging, and Ki-67 level were the independent prognostic factors for OS. Age, tumor quadrant, and T staging were the independent prognostic factors for DFS. The OS nomogram analysis showed that the OS of patients in the high-risk group was significantly improved by post-mastectomy radiotherapy (PMRT) ( P=0.001), while PMRT did not show an advantage in the low- and medium-risk groups ( P=0.057, P=0.099). The DFS nomogram analysis showed that DFS was significantly improved by PMRT in patients in the medium- and high-risk groups ( P=0.036, P=0.001), whereas the benefits from PMRT were not significant in the low-risk group ( P=0.475). Conclusions:For patients with pT 1-2N 1M 0 breast cancer after mastectomy, age ≤ 40 years, tumor located in the inner quadrant or central area, T 2 staging, 2-3 lymph node metastases, Ki-67>30% are the high-risk factors affecting clinical prognosis. The nomogram prediction model can screen the populations that can benefit from PMRT, providing reference for clinical decision-making.