Objective To explore the effect of management model of clinical pharmacists participating in multidisciplinary collaborative diagnosis and treatment(MDT)for new anti-tumor drugs in the national medical insurance drug negotiation(hereinafter referred to as"national negotiation"),including efficacy,safe-ty,economy and rationality.Methods The medical records of 326 cases using novel anti-tumor drugs by na-tional negotiation and conforming to the including and excluding standards in this hospital from July 2018 to June 2023 were retrospectively analyzed.The patients were divided into the MDT group(n=122)and non-MDT group(n=204).The patients diagnosed as non-small cell lung cancer(NSCLC)in the two groups were extracted and defined as the MDT-NSCLC subgroup(n=41)and non-MDT-NSCLC subgroup(n=77).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR)and the indexes such as survival quality and medical quality control were compared between the groups.Results The median PFS in the two groups was 12.7 months and 8.0 months,the median OS was 75.2 months and 56.3 months,DCR was 96.72％and 81.86％respectively,and the differences were statistically significant(P＜0.05).The COX multivariate regression analysis indicated that the HR value of clinical pharmacists participating in MDT was higher than the other influencing factors.The median PFS time in the MDT-NSCLC subgroup and non-MDT-NSCLC subgroup was 10.5 months and 6.7 months,DCR was 97.30％and 75.64％respectively,and the differences were statistically significant(P＜0.05),the median OS time was 55.1 months and 40.3 months respectively,and the difference was statistically significant(P＞0.05).The COX multivariate regression anal-ysis indicated that the HR value with clinical pharmacists participating in MDT was higher than the other in-fluencing factors;The adverse reaction occurrence rate in the MDT group and non-MDT group was 45.9％and 58.3％respectively,and the difference was statistically significant(P＜0.05).The KPS score after treatment in the MDT group was higher than that in the non-MDT group,and the difference was statistically significant;in the aspect of medical quality control,the average drug proportion in the MDT group and non-MDT group was 63.93％and 64.54％respectively,the rational drug rate of comments on prescription was 98.36％and 88.73％respectively,the patient satisfaction average value was 90.69 points and 87.36 points respectively and the differences were statistically significant(P＜0.05).Conclusion Clinical pharmacists participating in MDT related to novel anti-tumor drugs by national negotiation is beneficial to improve the therapeutic effects,living quality and patient satisfaction,also benefit to management and control of off-label drug use and medical quality control indexes.

Objective:To establish and verify a simple clinical prediction model for obstructive sleep apnea syndrome(OSAS)in children.Methods:The clinical data of 95 children aged 2-12 years underwent polysomnography(PSG)were screened.The subjects with OAHI≤1 were included into non-OSAS group(n=22)and those with OAHI＞1 into OSAS group(n=73).Gender,age,body mass index(BMI),night pulse minimum oxygen saturation(SpO2),tonsil grading and adenoid grading of the 2 groups were compared and analyzed.Binary Logistic regression analysis was used to statistically analyze the data and establish a clinical prediction model for OSAS in children.Results:There was significant difference in age,BMI,SpO2,tonsil grading and adenoid grading between the 2 groups(P＜0.05),there was no significant gender difference(P＞0.05).The model equation was as follows:X=2.366-0.769(age-continuous variable)+0.248(BMI-continuous variable)-3.413(SPO2-continuous variable)+2.104(tonsil grade Ⅲ-Ⅳ"yes").The result of internally validated Hosmer-Lemeshow test was P=0.612(P＞0.05),AUC was 0.821(0.713-0.929,P＜0.01),sensi-tivity was 83.3％,specificity was 76.4％.The accuracy of external validation was 73.8％,the AUC was 0.805(0.664-0.943,P＜0.01),the sensitivity was 84.6％and the specificity was 75％.Conclusion:The predictive model may have good predictive efficacy for 2-12 years old children with OSAS,and may assist clinicians in diagnosing children with OSAS.

Olfactory epithelium, which detects and transmits odor signals, is critical for the function of olfactory system. Olfactory epithelium is able to recover spontaneously after injury under normal circumstances, but this ability is dampened in certain diseases or senility, which causes olfactory dysfunction. The olfactory epithelium consists of basal cells, sustentacular cells and olfactory sensory neurons. In order to develop an olfactory epithelial organoid containing multiple olfactory cell types in vitro, we used three-dimensional culture model and small molecules screening. This organoid system consists of horizontal basal-like cells, globose basal-like cells, sustentacular-like cells and olfactory sensory neurons-like cells. Through statistical analysis of clone diameter, immunofluorescence staining and qPCR detection of the expression level of related marker genes. We identified a series of growth factors and small molecule compounds that affected the proliferation, composition and gene expression of the organoids. CHIR-99021, an activator of Wnt signaling pathway, increased the colony formation and proliferation rate of olfactory epithelial organoids and the expression level of marker genes of olfactory sensory neurons-like cells. In addition, each factor in the culture system increased the proportion of c-Kit-positive globose basal-like cell colonies in organoids. Moreover, EGF and vitamin C were both beneficial to the expression of horizontal basal-like cell marker genes in organoids. The established olfactory epithelial organoid system mimicked the process of olfactory epithelial stem cells differentiating into various olfactory epithelial cell types, thus providing a research model for studying olfactory epithelial tissue regeneration, the pathological mechanism of olfactory dysfunction and drug screening for olfactory dysfunction treatment.
Humans ; Olfactory Mucosa/metabolism* ; Epithelial Cells ; Organoids/metabolism* ; Olfaction Disorders/metabolism*

【Objective】 To analyze the risk factors for intraoperative massive red blood cell (RBC) transfusion in patients with Stanford type A aortic dissection (TAAD), in order to develop a risk-prediction model and validate its predictive effect. 【Methods】 The clinical data of 233 patients with TAAD admitted to our hospital from July 2018 to June 2021 (modeling set) were retrospectively analyzed. They were divided into routine transfusion group (n=128, RBC≤8 U) and massive transfusion group (n=105, RBC>8 U). Risk factors for intraoperative massive RBC transfusion in TAAD patients were analyzed by multivariate logistic regression and a risk prediction model was developed. Calibration curve and receiver operating characteristic (ROC) curve were used to assess the accuracy and discrimination of the model. In addition, 61 TAAD patients admitted to our hospital from July 2021 to May 2022 (validation set) were used for external validation. 【Results】 The rate of intraoperative massive RBC transfusion in 233 TAAD patients was 45.06% (95% CI: 38.59%-51.69%). Logistic analysis showed that women, age >50 years, preoperative Hb≤131.50 g/L, intraoperative bleeding >720 mL, and CPB time >155 min were independent risk factors for massive intraoperative RBC transfusion (P<0.05). The intraoperative risk prediction model formula for massive RBC infusion was: -4.427+ 0.925×gender+ 1.461×age+ 2.081×preoperative Hb+ 1.573×bleeding volume+ 2.823×CPB time. The area under the ROC curve of the modeling set and validation set were 0.904 (95% CI: 0.865-0.943) vs 0.868 (95%CI: 0.779-0.958), and the slopes of the calibration curves all converged to 1, indicating that the model predicted the risk of intraoperative massive RBC infusion in TAAD patients in good consistency with the actual risk of massive infusion. The decision curve shows that the model exhibits a positive net benefit with a threshold probability of 0.15-0.67 and has a high clinical application value. 【Conclusion】 The prediction model constructed based on the risk factors of intraoperative massive RBC infusion in TAAD patients can effectively predict the risk of intraoperative massive RBC infusion with high clinical predictive efficacy.

45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.
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Adenocarcinoma of Lung/genetics* ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Female ; Humans ; Indoles ; Lung Neoplasms/genetics* ; Mutation ; Quinolines

Objective: To evaluate the value of cerebrospinal fluid markers expecially total-tau protein (T-tau), phosphorylated-tau protein (P-tau) in diagnosis and differentiation of sporadic Creutzfeldt-Jakob disease (sCJD). Methods: sCJD (according to 2009 Brain criteria, 2018 Neurology amended criteria), Alzheimer's disease (AD; the National Institute on Aging at National Institutes of Health and the Alzheimer's Association revised guidelines 2011 criteria) and other patients without cognitive impairment, matched for sex and age, in the Department of Neurology, Peking Union Medical College Hospital from 2018 to 2019 were enrolled. Twelve sCJD patients, 49 AD patients and 14 normal controls were enrolled. Cerebrospinal fluid (CSF) specimens were collected through gravity dropping directly, and further stored in -80 ℃ and disposed according to widely used standards. The levels of T-tau and P-tau were measured by ELISA. The data on electroencephalogram and neuroimaging findings of sCJD patients were recorded. Moreover, specimens of sCJD patients were sent to the Chinese Center for Disease Control and Prevention to test 14-3-3 protein and PRNP genotype. Results: Using Mann-Whitney U test, T-tau concentrations were found higher in patients with sCJD (1 211(448, 2 227) pg/ml) than in AD patients (549(314, 1 078) pg/ml; U=178, P=0.034 9), and both groups had higher T-tau than the control group (127(79, 192) pg/ml; U=20, 73, P<0.01). The level of P-tau was significantly increased in AD patients (72(58,109) pg/ml) compared to the control group (27(15, 42) pg/ml; U=82, P<0.01), but not in sCJD patients (32(24, 47) pg/ml). The T-tau/P-tau ratio was higher in sCJD patients (29.77(20.01, 54.53)) than in AD patients (7.45(4.79, 10.43); U=87, P<0.01). Twelve sCJD patients had cotical hyperintensity on diffusion weighted imaging and five had periodic three-phase waves on electroencephalogram. Nine sCJD patients, whose CSF samples were tested in the Chinese Center for Disease Control and Prevention, carried an M/M genotype at codon 129 and E/E at codon 219. Conclusion The CSF tau level and T-tau/P-tau ratio are significantly increased in sCJD, which may promote the diagnosis and differentiation of sCJD in routine clinical setting.

Objective: To observe the temperature changes of skin on patients with cold and dampness syndrome by using the non-contact infrared human body thermometer and infrared thermal imager to treat the patients with cold and dampness syndrome by Jin-Bohua national famous Chinese medicine practitioners using the "Mountain Burning Manipulation by Jin-Shi" method to clarify the clinical thermal effects of the "Heat-producing Needling" method. Methods: This study included sixty patients with cold and dampness syndrome who met the enrollment conditionsfrom November 2015 to October 2017. In a room with fixed temperature, the patients were treated by "Heat-producing Needling" method. By using a non-contact infrared human body thermometer and infrared thermal imaging technology, this study observed the skin temperature changes in Quchi and Hegu, Zusanli and Chongyang before needling, immediately afterneedling, 15 minutes after needling, and 30 minutes after needling. Results: After the "Mountain Burning Manipulation by Jin-Shi" treatment, the temperature of local skin surface at acupoints of upper and lower limbs increased with different degrees and the skin temperature reached the highest level when the needle was kept for 15 minutes. The upper limbs' result indicated that skin temperature increased with significant differences in acupuncture of Quchi point for immediately, 15 minutes and 30 minutes as compared with that before acupuncture. It was found that the skin temperature at Hegu point for 15 minutes have a significant increase than before and immediately after acupuncture. The skin temperature of Hegu point lasted 30 minutes, which was significantly higher than before and immediately after acupuncture. Compared with Hegu point, Quchi point has higher skin temperature immediately after acupuncture (t=3.793, P=0.034). The lower limbss' results indicated that skin temperature at Zusanli point increased with significant differences in Zusanli point for immediately needling, 15 minutes and 30 minutes as compared respectively with that beforeneedling. It was found that the skin temperature at Chongyang point for 15 minutes had a significant increase than before and immediately after acupuncture. The skin temperature at Chongyang point for 15 mins had a significant increase than before and immediately afterneedling. The skin temperature of Zusanli point was higher than that of Chongyang point (t=3.794, P=0.034) immediately afterneedling. Conclusions This study demonstrates that the "Mountain Burning Manipulation by Jin-Shi" method has a clear clinical thermal effect on both local and peripheral longitude of patients with cold dampness syndrome.

Objective To analyze Professor Wu Weiping's medication rules on treating the onset of bronchial asthma based on data mining.Methods The patients'records and prescriptions of Professor Wu Weiping on treating the onset of bronchial asthma were collected and collated,and the frequency and regularity of drug combinations were researched by using the association rules of TCM inheritance support system to analyze the medication experience of Professor Wu Weiping.Results By analyzing the 249 prescriptions of 61 patients,drug properties of the prescription:cold (45.6％),warm (42.6％),bitter(37.9％),pungent (27.5％).Channel tropism:lung,spleen,liver,stomach.The top 10 herbal medicine are Qingbanxia,Chaihu,Fangfeng,Huangqin,Mahuang,Wuweizi,Wumei,Qianhu,Chishao,Kuxingren.The top 3 treatment principle is reducing phlegm,expelling wind evil and regulating qi.Xiaochaihu decoction and Guomin decoction were showed in the article.Conclusions Data dining could help to discover the rules of Professor Wu Weiping's treatment of the onset of bronchial asthma.The cold and warm drugs,acrid and bitter drugs were used together frequently,while the drugs belonging to the lung,spleen,liver and stomach meridians were used commonly.The evil of phlegm,qi and wind were paid attention to eliminate pathogen.

Objective: To explore the value of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA) enhanced MRI T₁ mapping in diagnosing and distinguishing dysplastic nodule (DN) and hepatocellular carcinoma (HCC) with different degrees of differentiation. Methods: A retrospective study in the first affiliated Hospital of Guangxi Medical University from September 2015 to December 2017 was conducted. Seventy-one patients with HCC or DN (a total of 79 lesions) that confirmed by biopsy or surgical pathology findings. Seventy-nine lesions were divided into DN (n=10), well differentiated HCC (n=15), moderately differentiated HCC (n=36) and poorly differentiated HCC (n=18) according to histopathology. All the patients underwent plain MRI scan and Gd-EOB-DTPA-MRI T₁ mapping before surgery or needle biopsy. The T₁ values of each lesion and non-tumorous liver parenchyma were measured on 20 min hepatobiliary phase (HBP) T₁ mapping after Gd-EOB-DTPA administration, respectively. The increment rate of T₁ value in lesions relative to non-tumorous liver parenchyma were calculated. One-way ANOVA was used to compare the differences of T₁ value and the increment rate of T₁ value of DN and 3 groups of HCC with different degrees of differentiation. Spearman correlation was used to evaluate the correlation between T₁ mapping parameters and the malignancy degree of DN and HCC. Area under the receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T₁ mapping parameters in the differential diagnosis of DN and HCC with different degree of differentiation. Results: Significant differences were found in T₁ value and increase rate of T₁ value of DN and HCC with different degrees of differentiation (P< 0.05). The T₁ value and increase rate of T₁ value showed an increasing trend from DN to poorly differentiated HCC after enhancement. The T₁ value and increase rate of T₁ value were positively correlated with the malignancy of DN and HCC (r=0.418 and 0.634, P<0.01). There were significant differences in the increase rate of T₁ value between well-differentiated HCC and moderately-differentiated, well-differentiated HCC and poorly-differentiated HCC, respectively (P<0.05). The area under ROC curve of T₁ value and the increase rate of T₁ value for differentiating DN from well-differentiated, moderately differentiated and poorly differentiated HCC was 0.933, 0.928, 0.939 and 0.867, 0.961, 0.961, respectively. The area under ROC curve of the increase rate of T₁ value for differentiating well-differentiated HCC from moderately-differentiated, well-differentiated HCC from poorly-differentiated HCC was 0.770 and 0.844, respectively. Conclusions Gd-EOB-DTPA enhanced MRI combined with T₁ mapping can provide valuable diagnostic information for identifying DN and HCC with different degrees of differentiation.

Objective:To analyze the correlation between arch width and different vertical facial skeletal types of the adults with individual normal occlusion.Methods:52 adults with individual normal occlusions(females 31,males 21) were included.According to the values of mandibular plane angle MP-FH,SN-MP measured on CBCT image the subjects were divided into 3 groups(13 cases with highangle,19 with average-angle and 20 with low-angle groups).12 parameters were measured for each sample,including maxillary and mandible arch width and alveolar arch width between canines,between first premolars and between first molars,the difference between the maxillary arch width and mandibular arch width were calculated.The data were statistically analyzed by one-way ANOVA and Pearson~ rank correlation test.Results:In the group of high-angle,average-angle and low-angle the alveolar arch width(mm) between maxillary canines was 38.03 ± 1.90,39.65 ± 1.80 and 39.78 ± 2.20 respectively(P ＜ 0.05).The arch width between maxillary first premolars of high-angle group(37.01 ± 1.60) was smaller than that of low-angle group(38.65 ± 1.30).The arch width difference in canine area between maxillary and mandibular alveolar in high-angle,average-angle and low-angle groups was 7.39 ± 1.82,9.04 ± 1.43 and 9.26 ± 1.67 respectively(P ＜0.05);in maxillary first premolars area in high-angle(6.8 ± 1.59) was smaller than that in averageangle(7.79 ± 1.09),maxillary and mandibular arch width showed no statistical difference.Pearson correlation test showed that among 3 groups,upper and lower alveolar arch width difference in canine and first premolars area was negatively correlated with the mandibular plane angle.while upper and lower arch width difference showed no statistical correlation with the mandibular plane angle.Conclusion:The maxillary middle arch width of the subjects with individual normal occlusion was correlated with vertical facial type.