ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic［water activity（A_w）］ and microscopic（water molecular mobility）， which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method， and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient（R²） was closer to 1， residual sum of squares（RSS） was closer to 0 and Akaike information criterion（AIC） was smaller. According to the optimal model， the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ was calculated. Low-field nuclear magnetic resonance（LF-NMR） was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression， the absolute safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ were 9.59%， 7.96% and 7.68%， and the relative safe moisture contents were 13.05%， 11.99%， 11.77%， respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures， namely bound water T₂₁ and free water T₂₂. During the process of hygroscopic absorption， bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents， and the R² were 0.959 9， 0.911 8 and 0.974 7 at 25， 35， 45 ℃， respectively. When A_w<0.57， T₂₁ did not change， and the water molecular mobility remained unchanged. When A_w>0.57， T₂₁ showed an increasing trend， and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%， 6.81% and 6.25% when the water molecular mobility increased at 25， 35， 45 ℃， respectively. ConclusionCombined with the theory of water activity and water molecular mobility， 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces， this study can provide reference for determining the safe storage moisture content of other decoction pieces.

This study was performed to explore the impact of glutamine(Gln)on the anti-tumor immune response of CD8+ T cells and its mechanism.TCGA database was used to analysis the relationship between tumor Gln metabolism and the quantity and functionality of infiltrating CD8+ T cells.CRISPR/Cas9 was employed to knock down GLS expression in mouse MC38 cells,and a mouse tumor model was established.Flow cytometry was conducted to assess tumor proliferation,apoptosis,and the quantity and functionality of tumor-infiltrating immune cells.Lymphocytes isolated from health individuals were treated with Gln-deficient media,complete media or media supplemented with GSH,RSL3 in vitro.Then the apoptosis,the expression levels of GPX4,Lipid-ROS,and effector function protein of CD8+ T cells were detected by flow cytometry.Furthermore,RNA-seq was performed to analyze the differential gene expression on the Gln-depleted CD8+ T cells.Data showed that tumor Gln metabolism was inversely associated with the quantity and functionality of tumor-infiltrating CD8+ T cells.Low expression of GLS in MC38 cells could inhibit C57BL/6 tumor growth,decrease Ki-67 expression,promote casepase-3 expression,increase the amount of tumor-infiltrating immune cells,suppress PD-1,TIM-3,and LAG-3 expression,and enhance CD137,CD107a,IFN-γ and TNF-α expression in tumor-infiltrating CD8+ T cells.RNA-seq results indicated an upregulation of ferroptosis genes TFRC,HMOX1,CYBB and SLC7A11 in CD8+ T cells following glutamine deficiency.Gln deficiency led to lower CD137,CD107a,IFN-γ,GSH,GPX4 expression,increased Lipid-ROS level,and caused cell death in CD8+ T cells.Supplementation of GSH upregulated GPX4 expression,downregulated Lipid-ROS level,and increased IFN-γ secretion in CD8+ T cells.In conclusion,Gln deficiency inhibits the effector function of CD8+ T cells by inducing ferroptosis,and promotes tumor growth.

ObjectiveModern scientific methods and techniques were used to scientifically characterize the traditional softening process of Corydalis Rhizoma， so as to clarify the scientificity and rationality of the traditional process， and provide reference for inheriting the processing methods and experience of traditional Chinese medicine. MethodLow-field nuclear magnetic resonance imaging （LF-NMR/MRI） was used to characterize the water types and distribution in the softening process of Corydalis Rhizoma. Samples during the softening process was cut into thick slices and its section was observed by stereoscopic microscope. High performance liquid chromatography （HPLC） was employed to determine the content change of tetrahydropalmatine during the softening process with the mobile phase of methanol-0.1% phosphoric acid solution （60∶40， triethylamine regulated to pH 6.5） and detection wavelength at 280 nm. The determination method of softening endpoint of Corydalis Rhizoma was simulated by texture analyzer （hand pinch method）， and the softening degree of the finished products was determined after optimizing the relevant parameters. ResultLF-NMR/MRI showed that the water could penetrate through the core and distribute evenly in Corydalis Rhizoma softened by Zhangbang method. The water first entered into the medicinal material from the epidermis and stem marks in the soaking stage as the form of free water， and then penetrated into the inner core to achieve redistribution in the moistening stage. Under stereoscopic microscope， it was observed that Corydalis Rhizoma softened by the Zhangbang method could be sliced well， but the core bursting slices were easy to appear if the softening time was not enough， and the softening of samples was caused by the keratine-like powder after absorbing water. HPLC measurement showed that the loss of tetrahydropalmatine in the softening method was small， its content decreased about 5% in the soaking process， and its content was almost unchanged during the moistening process. The softening degree of Corydalis Rhizoma could be quantified by the texture analyzer， and the optimum parameters were 2 mm·s^-1 of speed before test， test speed and speed after test， 20 g of the trigger force， 20% of compression degree. The compressive force of the qualified softened Corydalis Rhizoma was 12.75-15.69 N with the relative standard deviation （RSD） of 6.8%. ConclusionModern scientific methods and techniques can characterize the scientificity and rationality of the traditional processing methods， and confirm that the Zhangbang softening method has the advantages of high efficiency， convenience and small loss of index components. The texture analyzer can simulate the softening endpoint judgment method （hand pinch method）， and realize the goal from subjective experience judgment to objective technology quantification， which has a good demonstration role for the modern inheritance of traditional processing technology.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Objective:To understand the current situation of the demand for humanistic care of schizophrenics in convalescence and analyze the influencing factors, so as to provide the basis for clinical nurses to carry out targeted humanistic care for patients.Methods:A self-produced scale with a total score of 49-245 was used to investigate 516 convalescent period schizophrenic patients in 18 tertiary mental health institutions in 13 provinces of China, single factor analysis and multiple regression analysis were performed on their influencing factors.Results:The Likert 5-point scoring method was used. The overall score of the nursing care needs of hospitalized schizophrenic patients was (202.85±35.06) points, and the average score of total items were (4.14±0.16) points. Multiple linear regression results showed female ( B=0.100, P=0.024), stable marriage ( B=-0.098, P=0.026),high school (including secondary school) Education ( B=-0.107, P=0.018), family per capita monthly income of 2 000 yuan or above ( B=0.093, P=0.043),central region ( B=-0.110, P=0.014) were the main factors that affect the demand for humanistic care of inpatients with schizophrenia in convalescence. Conclusion:The hospitalized schizophrenic patients have higher and diversified needs for humanistic care. Patients with different genders, marital status, education level, monthly family income and living area have different needs for humanistic care. Individualized and standardized nursing should be given according to the actual situation of patients' needs to provide a more supportive environment for their rehabilitation.

Objective To evaluate the effect of percutaneous coronary intervention (PCI) on anxiety and depression among patients with coronary heart disease (CHD). Methods A total of 600 CHD patients were divided into the stent group (n = 400) and the non-stent group (n = 200) according to stent implantation during coronary angiography, and 400 cases in the stent group were further divided into the intervention group (n = 200) and the non-intervention group (n = 200) according to post-stenting psychological interventions. The anxiety and depression were scored using self-rating anxiety and depression scales 1 day after admission, 1 day after PCI and at discharge from hospital, and the anxiety and depression scores were compared at different time points. Results The mean age, sex ratio, hemoglobin, total cholesterol, triglyceride, high-density lipoprotein cholesteroland low-density lipoprotein cholesterol levels were comparable among the three groups (P > 0.05). There were no significant differences among the three groups in terms of anxiety or depression scores one day after admission (P > 0.05). One day after PCI, the anxiety and depression scores were significantly higher among CHD patients in the intervention and non-intervention groups than in the non-stent group (P < 0.05), and the anxiety (t = 11.21, P < 0.01; t = 9.96, P < 0.01) and depression scores (t = 8.56, P < 0.01; t = 6.73, P < 0.01) were significantly higher in the intervention and non-intervention groups one day after PCI than one day after admission. At discharge from hospital, there were significant differences among the three groups in terms of anxiety and depression scores (P < 0.05), and the anxiety (t = 21.57, P < 0.01; t = 15.77, P < 0.01) and depression scores (t = 24.33, P < 0.01; t = 15.01, P < 0.01) were significantly higher in the intervention and non-intervention groups at discharge from hospital than one day after PCI, while the anxiety and depression scores were significantly lower among CHD patients in the intervention group than in the non-intervention group (P < 0.05). Conclusion The anxiety and depression are aggravated among CHD patients after PCI, and psychological interventions may alleviate the anxiety and depression.

OBJECTIVE：To establish the method for online rapid detection of related indexes in the concentration process of Huagai san extraction solution ，and to provide reference for judgment of concentration end point. METHODS ：Online diagram of 73 concentrated samples in the concentration process of Huagai san extraction solution were drawn by NIRS online collection equipment. The partial least squares （PLS）method was used to establish the NIRS quantitative calibration model of 5 related indexes （concentration density ， solid content ， the contents of amygdalin ， ephedrine hydrochloride and pseudoephedrine hydrochloride）. Another 15 samples were used to validate the model ，and the correlation of predicted value and measured value was analyzed. RESULTS ：The correlation coefficients （R2）of the concentration density ，solid content ，the contents of amygdalin ， ephedrine hydrochloride and pseudoephedrine hydrochloride in the quantitative calibration model were 0.982 5，0.999 9，0.998 3， 0.999 4 and 0.999 3，respectively；the root mean square errors of calibration （RMSEC）were 0.001 6，0.025 1，0.014 7，0.001 8 and 0.000 9；the root mean square errors of cross validation （RMSECV）were 0.002 1，0.035 8，0.033 6，0.006 3 and 0.001 3， respectively. After validation by 15 samples，root mean square errors of prediction （RMSEP）were 0.003 2，0.024 6，0.021 5， 0.007 7 and 0.005 9，respectively. CONCLUSIONS ：The established quantitative calibration model has good predictability and can provide basis for online judgment of concentration end point of Huagai san extraction solution.

Objective: To analyze the status of domestic surgical treatment of synchronous peritoneal carcinomatosis from colorectal cancer in China. Methods: Clinicopathological data of patients who underwent surgery from October 2003 to October 2018 in 16 domestic medical centers was retrospectively analyzed. Excel database was created which covered 77 fields of 7 parts: baseline information of patients, laboratory tests, imaging tests, chemoradiotherapy information, intra-operative findings, postoperative pathology and follow-up data. The Wilcoxon rank-sum test was used for comparison of the measurement data between groups. The χ² test was used for comparison of the categorical data between groups. The survival curve was calculated by the Kaplan-Meier method. Results: Of the 1 003 patients, there were 575 male and 428 female patients with the age of (58.5±14.1) years (range: 18 to 92 years). In a total of 920 patients, the carcinoma of sigmoid colon was performed in 292 cases (31.8%) with the highest ratio. The proportion of patients with liver metastasis and lung metastasis were 27.9% (219/784) and 8.3% (64/769). Preoperative detection of carcino-embryonic antigen level was the most common method in China (87.74%, 880/1 003), and the positive rate was 64.5% (568/880). The correct rate of preoperative imaging tests was 40.7% (280/688). The ratio of peritoneal carcinomatosis index (PCI) scores between 0 and 10 was the highest (59.6%, 170/285). Two hundred and sixty-two (27.0%) patients were performed by totally laparoscopic operation in 971 patients. The resection of primary tumor was performed in 588 of the 817 patients (72.0%). In a total of 457 cases, 253 (55.4%) patients were performed cytoreduction which group scored completeness of cytoreduction (CCR) 0. The postoperative hyperthermic intraperitoneal chemotherapy was implemented in 70 of the 334 cases (21.0%). Among 1 003 cases, 562 cases (56.03%) had complete follow-up data and the median overall survival was 15 months. The primary tumor resection and the CCR scores were affected by the PCI scores. The patients underwent primary tumor resection (187/205 vs. 26/80, χ²=105.085, P=0.000) and the patients were performed cytoreduction which scored CCR 0 or CCR 1 (162/204 vs. 8/78, Z=-10.465, P=0.000) had significant difference between the groups of PCI<20 and ≥20. There was a close correlation between the surgical method and the CCR scores (Z=-3.246,P=0.001).When the maximum degree of tumor reduction was planned, most surgeons would choose laparotomy. The overall survival time was longer in patients with primary tumor resection (P=0.000). The median survival time was 18.6 months in the group of primary tumor resection. Conclusions It is difficult to diagnose the synchronous peritoneal carcinomatosis from colorectal cancer before the operation. Primary tumor resection has an obvious effect to prolong the survival time. It is necessary to standardize the treatment of peritoneal metastasis.

OBJECTIVE： To prepare Paclitaxel-sorafenib-PLGA-loaded embolic microspheres， and to establish a method for the content determination and investigate their in vitro drug release characteristics. METHODS： Paclitaxel-sorafenib-PLGA-loaded embolic microspheres were prepared by emulsification-solvent evaporation method. HPLC method was used to determine the contents of paclitaxel and sorafenib in Paclitaxel-sorafenib-PLGA-loaded embolic microspheres； drug-loading amount and encapsulation efficiency were calculated. The determination was performed on Agilent TC-C18 column with mobile phase consisted of water-acetonitrile （40 ∶ 60，V/V） at the flow rate of 1.0 mL/min. The detection wavelength was set at 228 nm， and column temperature was 28 ℃. The sample size was 10 μL. The morphology of the microspheres was observed by optical microscopy and scanning electron microscopy. The particle size and granularity distribution of microspheres were measured by laser granularity analyzer. The release rates of paclitaxel and sorafenib were determined by HPLC under physiological temperature （37 ℃）. The reaction rate constants were predicted by Arrhenius equation at 37 ℃， and compared with the measured value （37 ℃）. RESULTS： The linear range of paclitaxel and sorafenib were 2.0-400.0 μg/mL （both r＝0.999 6）. The quantitative limits were 1.902 6 and 1.890 2 μg/mL， and detection limits were 0.985 5 and 1.264 5 μg/mL， respectively. RSDs of precision， stability and reproducibility tests were all lower than 2％. The recoveries were 99.00％-102.91％ （RSD＝1.12％， n＝9） and 98.39％-102.96％ （RSD＝1.94％， n＝9）. The surface of the microspheres were spherical， smooth and no protuberance and no adhesions. The average particle size was （139±1.16） μm. Drug-loading amounts of paclitaxel and sorafenib were 1.12％ and 0.85％， respectively. The encapsulation efficiency were 73.11％ and 58.65％， respectively. Accumulative release rates were （71.83±3.96）％ and （81.44±6.02）％ within 41 d at 37 ℃. RSDs for relative standard deviation of prediction reaction rate constant to measured value were less than 10％ for paclitaxel and sorafenib. The similarity factors were 83.53 and 73.95. CONCLUSIONS： Paclitaxel-sorafenib-PLGA-loaded embolic microspheres are successfully prepared. The microspheres have good morphology and sustained release. The predicted release curve is well correlated with the measured release curve. Established determination method is simple and stable.