Objective:To summarize the clinical and genetic features of neuroinflammation, autoinflammation, splenomegaly and anemia (NASA) syndrome and investigate the pathogenic mechanism.Methods:The clinical data of 2 patients diagnosed with NASA syndrome at Department of Pediatrics, Peking Union Medical College Hospital were retrospectively analyzed. Variants were identified by gene panel sequencing and confirmed by Sanger sequencing. The function of IRAK4 gene variants was studied in vitro.Results:Among the 2 patients, case 1 was an 8-year-old girl and case 2 was a 10-year-old boy. Both patients presented in early childhood with anemia and hepatosplenomegaly. Case 1 was also experienced recurrent seizures. Laboratory examinations showed elevated inflammatory markers and neuroimaging revealed bilateral basal ganglia calcification. In case 2, anemia and inflammation markers were well controlled after treatment with tocilizumab, while case 1 succumbed to recurrent seizures. Genetic tests verified compound heterozygous variants in IRAK4 gene: case 1 carries a nonsense variant c.592G>T (p.G198X) and a missense variant c.248A>C (p.D83A), which were respectively from the parents; case 2 carries a c.831+3A>G variant and a frameshift variant c.540delT (p.F180Lfs*26), and the former was inherited from the father and the latter from the mother. The reverse transcription and Sanger sequencing results confirmed that c.831+3A>G variant led to exon 7 skipping. In vitro studies indicated that c.592G>T, c.540delT and c.831+3A>G variants resulted in truncated interleukin-1 receptor-associated kinase-4 (IRAK4) protein while c.248A>C do not cause changes in IRAK4 protein expression level and protein length.Conclusions:NASA syndrome should be considered in children with early-onset anemia, hepatosplenomegaly, recurrent seizures, elevated inflammatory markers and intracranial calcification. IRAK4 gene variants may lead to impaired anti-inflammatory function of IRAK4 protein, contributing to the autoinflammatory phenotype.

OBJECTIVE To construct a prediction model for the efficacy of serotonin-norepinephrine reuptake inhibitor(SNRI)in inpatients with moderate and severe depression by using a machine learning method.METHODS The case records of inpatients with moderate and severe depression treated with SNRI antidepressants were collected from a third-grade class-A hospital in Xinjiang from January 2022 to October 2024;those patients were divided into effective group and ineffective group based on the Hamilton depression scale-24 score reduction rate.After screening the characteristic variables related to the therapeutic efficacy of SNRI drugs through LASSO regression,five prediction models including support vector machine,k-nearest neighbor,random forest,lightweight gradient boosting machine and extreme gradient boosting were constructed using the training set.Bayesian optimization was used to adjust the hyperparameters of these models.The performance of the models was evaluated in the validation set to select the optimal model.The Shapley additive explanations method was used to perform explainable analysis on the best model.RESULTS The medical records from 355 hospitalized patients with moderate and severe depression were collected,comprising 285 cases in the effective group and 70 cases in the ineffective group,resulting in an overall therapeutic response rate of 80.28%.After feature variable screening,five characteristic variables for therapeutic efficacy were obtained,including Hamilton anxiety scale,blood urea nitrogen,combination of anti-anxiety drugs,drinking history,and first onset of the disease.Compared with other models,the random forest model performed the best.The area under the receiver operating characteristic curve was 0.85,the area under the precision-recall curve was 0.87,the accuracy was 0.74,and the recall rate value was 0.75.CONCLUSIONS The random forest model constructed based on five characteristic variables demonstrates potential for predicting the therapeutic efficacy of SNRI antidepressants in hospitalized patients with moderate and severe depression.

Objective:To summarize the clinical and genetic features of neuroinflammation, autoinflammation, splenomegaly and anemia (NASA) syndrome and investigate the pathogenic mechanism.Methods:The clinical data of 2 patients diagnosed with NASA syndrome at Department of Pediatrics, Peking Union Medical College Hospital were retrospectively analyzed. Variants were identified by gene panel sequencing and confirmed by Sanger sequencing. The function of IRAK4 gene variants was studied in vitro.Results:Among the 2 patients, case 1 was an 8-year-old girl and case 2 was a 10-year-old boy. Both patients presented in early childhood with anemia and hepatosplenomegaly. Case 1 was also experienced recurrent seizures. Laboratory examinations showed elevated inflammatory markers and neuroimaging revealed bilateral basal ganglia calcification. In case 2, anemia and inflammation markers were well controlled after treatment with tocilizumab, while case 1 succumbed to recurrent seizures. Genetic tests verified compound heterozygous variants in IRAK4 gene: case 1 carries a nonsense variant c.592G>T (p.G198X) and a missense variant c.248A>C (p.D83A), which were respectively from the parents; case 2 carries a c.831+3A>G variant and a frameshift variant c.540delT (p.F180Lfs*26), and the former was inherited from the father and the latter from the mother. The reverse transcription and Sanger sequencing results confirmed that c.831+3A>G variant led to exon 7 skipping. In vitro studies indicated that c.592G>T, c.540delT and c.831+3A>G variants resulted in truncated interleukin-1 receptor-associated kinase-4 (IRAK4) protein while c.248A>C do not cause changes in IRAK4 protein expression level and protein length.Conclusions:NASA syndrome should be considered in children with early-onset anemia, hepatosplenomegaly, recurrent seizures, elevated inflammatory markers and intracranial calcification. IRAK4 gene variants may lead to impaired anti-inflammatory function of IRAK4 protein, contributing to the autoinflammatory phenotype.

Objective:To investigate the application effect of the blended teaching model of "intelligent teaching" and "wisdom learning" in the practice teaching of integrated traditional Chinese and Western medicine in internal medicine.Methods:According to the principle of randomization, 54 interns in Class 1 of integrated traditional Chinese and Western medicine in the grade of 2019 were selected as control group and received traditional teaching, and 56 interns in Class 2 were selected as observation group and received blended teaching with "intelligent teaching" and "wisdom learning". After 6 months of internship, the two groups were compared in terms of the scores of theoretical assessment (basic theoretical knowledge and professional theoretical knowledge), clinical practice ability [Leicester Assessment Package (LAP)], and degree of satisfaction with teaching. SPSS 17.0 was used to perform the t-test and the chi-square test. Results:At the end of internship, compared with the control group, the observation group had significantly higher score of basic theoretical knowledge (41.53±3.42 vs. 38.71±3.38, P<0.05), score of professional theoretical knowledge (39.49±3.14 vs. 37.85±3.07, P<0.05), LAP score (84.32±6.65 vs. 78.46±6.17, P<0.05), and degree of satisfaction with teaching ( P<0.05). Conclusion:For interns majoring in integrated traditional Chinese and Western medicine, the blended teaching model of "intelligent teaching" and "wisdom learning" can strengthen their mastery of theoretical knowledge, enhance their clinical practice ability, and improve their degree of satisfaction with teaching.

OBJECTIVE To study the effects of the active component 17-hydroxy-jolkinolide B （HJB） of Euphorbia fischeriana on the proliferation and apoptosis of human triple-negative breast cancers （TNBC） MDA-MB-231 and MDA-MB-468 cells. METHODS MTT assay was adopted to detect the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation after treated with 0 （blank control），5，10，20，40，80 μmol/L HJB for 24， 48 and 72 h. Laser confocal microscope and flow cytometry were adopted to detect the apoptosis， mitochondrial membrane potential（MMP） and reactive oxygen species （ROS） of above 2 kinds of cells after treated with 0 （blank control）， 10，20，40 μmol/L HJB for 24 h. Western blot assay was used to detect the expressions of B cell lymphoma-2（ Bcl-2）， Bcl-2-associated X protein （Bax）， cytochrome-C （Cyt-C）， caspase-3， cleaved caspase- 3， caspase-9 and cleaved caspase-9. RESULTS Compared with blank control group， 5，10，20，40，80 μmol/L HJB could significantly increase the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation （P＜0.05）， in dose- and time- dependent trend. After 24 h treatment of HJB （10，20，40 μmol/L）， the apoptosis of above 2 kinds of cells increased， and the total apoptotic rate increased significantly （P＜0.05）； the mitochondrial membrane potential decreased significantly （P＜0.05）； the level of ROS increased significantly （P＜0.05）； the protein expressions of Bcl-2， caspase-3 and caspase-9 were decreased significantly （P＜ 0.05）， while the protein expressions of Cyt-C， Bax， cleaved caspase-3 and cleaved caspase-9 were increased significantly （P＜0.05）. CONCLUSIONS HJB can inhibit the proliferation of MDA-MB-231 and MDA-MB-468 cells， and induce their apoptosis.

In recent years, artificial intelligence (AI) has been widely applied in the field of drug discovery and development.In particular, natural language processing technology has been significantly improved after the emergence of the pre-training model.On this basis, the introduction of graph neural network has also made drug development more accurate and efficient.In order to help drug developers more systematically and comprehensively understand the application of artificial intelligence in drug discovery, this article introduces cutting-edge algorithms in AI, and elaborates on the various applications of AI in drug development, including drug small molecule design, virtual screening, drug repurposing, and drug property prediction, finally discusses the opportunities and challenges of AI in future drug development.

Objective:To investigate the feasibility and adverse reactions of simultaneous integrated boost (SIB) in volumetric modulated arc therapy (VMAT) for early breast cancer after breast-conserving surgery.Methods:A total of 67 patients with early breast cancer after breast-conserving surgery at Zhongshan People's Hospital from September 2019 to May 2021 were enrolled. All patients received VMAT-SIB to the whole breast and tumor bed. The total breast dose and tumor bed dose were 40.5Gy/15 times every 3 weeks and 48 Gy/15 every 3 weeks respectively. The exposure dose of organs at risk and acute adverse reactions of radiotherapy were evaluated.Results:The average doses of planning target volume of the whole brease (PTV WB) and planning target volume of the boost(PTV BOOST) were (42.0±2.1) Gy and (49.9±0.8) Gy, respectively. The V 95% and V 105% of PTV WB and PTV BOOST were (98.8±1.2)% and (31.4±11.3)%, (99.8±0.6)% and (22.9±10.2)%, respectively. The V 5Gy, V 20Gy, V 30Gy and mean dose (D mean) of ipsilateral lung were (52.4±12.0)%, (15.3±4.5)%, (6.7±2.2)% and (11.0±2.4) Gy respectively. The V 18Gy, V 40Gy and D mean of heart were 3.80% (0.48%,9.60%), 0 (0,0.16%) and (6.7±2.1) Gy respectively. At the end of radiotherapy, 19 patients (29%) of all 67 patients had no acute skin toxicity, 41 patients (61%) showed radiation erythema, 5 patients (7%) had radioactive dry peeling and 2 patients (3%) had wet peeling mainly located in the nipple, areola area and breast folds. None of the patients had grade 3-4 acute skin reactions. Breast swelling and breast pain were found respectively in 9 patients (13%) and 7 patients (10%). No local recurrence or distant metastases were observed during the follow-up period. The 2-year disease-free survival rate was 100%. Conclusions:VMAT combined with SIB is feasible in the treatment of early breast cancer. The adverse reactions of radiotherapy are mild and well tolerated.

OBJECTIVE：To study the potential mechanism of yam protein （DOT） in the prevention and treatment of diabetes-induced erectile dysfunction （DIED）. METHODS ：DIED model was induced by high-glucose and high-fat diet and intraperitoneal injection of streptozotocin （40 mg/kg）. The experiment was set up in the normal control group （normal saline ）， model group （normal saline ），DOT low-dose ，medium-dose and high-dose groups （0.3，0.6，0.9 mg/kg），sildenafil group （positive control ，4.4 mg/kg），with 9 rats in each group. In the stage of successful establishment of diabetes model and initiation of inducing DIED ，rats in each group were given relevant solution intragastrically ，once a day ，for consecutive 11 weeks. Body weight，fasting plasma glucose （FPG），the times and rate of penile erection ，fasting insulin （FINS），insulin resistance index （IR），the contents of endothelial nitric oxide synthase （eNOS）and cyclic guanosine monophosphate （cGMP）in penile cavernous tissue were determined so as to evaluate the intervention effects of DOT on DIED model rats. High-glucose damaged mice cavernous endothelial cells （MCECs）model was induced by 30 mmol/L glucose for 48 h，and then give DOT 125，250，500 μg/mL. The cell viability was detected so as to evaluate the effects of DOT on high-glucose damaged MCECs model. RNA-Seq mail：xingxin0902@163.com technology was adopted to screen the differentially expressed genes between normal MCECs and high-glucose damaged MCECs，high-glucose damaged MCECs and MCECs treated with 250 μg/mL DOT. Gene ontology（GO）function enrichment analysis and KEGG pathway enrichme nt analysis were performed for differentially expressed genes. The common differentially expressed genes between 2 groups were analyzed ，and mRNA expressions of six key genes were validated. RESULTS ：Different doses of DOT could reverse the reduction of body weight ，the increase of FINS and IR ，the reduction of the times and rate of penile erection ，the decrease of eNOS and cGMP contents in penile cavernous tissue of DIED model rats ；above indexes of DIED model rats were reversed significantly after treated with high-dose of DOT（P＜0.05 or P＜0.01）. 125，250，500 μg/L DOT could significantly improve the activity of high-glucose damaged MCECs （P＜0.05 or P＜0.01）. RNA-Seq technology showed that compared with normal MCECs ，a total of 48 differentially expressed genes were found in high-glucose damaged MCECs. Compared with high-glucose damaged MCECs ，a total of 779 differentially expressed genes were found in MCECs treated with DOT. The differentially expressed genes of 2 groups were mainly cellular process in biological process annotation ，cellular part in cell component annotation and binding molecular function in molecular function annotation ，which were mainly enriched in extracellular matrix receptor interaction pathway ，mismatch repair pathway ， phosphatidylinositol 3 kinase-protein kinase B （PI3K-Akt）signal pathway and so on. Among differentially expressed genes of 2 groups，13 common differentially expressed genes such as Aldh1a1，Abcc5，Tac1 were found. DOT could significantly reverse the expression of the above common differentially expressed genes in high-glucose damaged MCECs. After validation ，DOT could significantly reverse the mRNA expression of TGF-β3，Txnip，Aldh1a1，Loxl1，Mt1 and Mt2 in high-glucose damaged MCECs. CONCLUSIONS：DOT could improve the symptom of DIED model rats ，the mechanism of which may be related to biological pathway of inhibiting fibrosis and reducing oxidative stress ，so as to improve the endothelial function of cavernous body.

Objective:To preliminarily discuss the mechanism of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of lipid metabolism through regulating the imbalance of fibrinolytic system in rats with non-alcoholic fatty liver. Methods:The model of non-alcoholic fatty liver in rats was duplicated by high-fat diet feeding. Totally 60 adult Wistar rats were randomly divided into 6 groups (n=10 per group), namely the control group, the model group, Salvia miltiorrhiza group, Rrhizoma alismatis group, Salvia miltiorrhiza and Rrhizoma alismatis group,and Dongbaogantai group. The control group and the model group were given distilled water,and the other group was given Salvia miltiorrhiza,Rrhizoma alismatis,Salvia miltiorrhiza combined with Rrhizoma alismatis and Dongbaogantai,respectively. Rhizoma Alismatis decoction at high dose and low dose as well as Dongbaogantai was respectively adminis-trated in the designed groups,and the corresponding indices were detected 4 weeks later. Results:In the model control group,the con-tents of TC、TG、FFA in serum and the expression of PAI-1 were significantly elevated(P<0.05 or P<0.01),while the expression of t-PA was significantly reduced(P<0.01).After treatment,the contents of TC、TG、FFA in serum and the expression of PAI-1 in every treatment groups were reduced(P<0.01),while the expression of t-PA was elevated(P<0.01).Conclusion: Increasing the expres-sion of t-PA and reducing the expression of PAI-1 might be viewed as the mechanisms of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of non-alcoholic fatty liver disease.

[Objective] To explore the similarities and differences between ancient and modern physicians in treating "bone atrophy"so as to provide reference for clinical treatment of renal osteodystrophy, bone tuberculosis and osteoporosis. [Method] Summarizing the similarities and differences between ancient and modern physicians in etiology and pathogenesis and treatment of syndrome differentiation of bone atrophy by consulting the literatures. [Results] Ancient and modern physicians have connections and differences in treatment based on syndrome differentiation of bone atrophy.Ancient physicians who treated bone atrophy whose syndrome was evil invading XiGu, deficiency of spleen and kidney with coordinating meridian of Yangming, getting rid of evil obtained better effects and the syndrome of Qi deficiency and blood stasis, damage of Yin and Yang that treated with enriching Qi and activating blood, nourishing yin and tonifying yang as well. Modern physicians who treated bone atrophy whose syndrome was deficiency of spleen and kidney, dampness and blood stasis with nourishing kidney and spleen, activating blood and draining turbidity obtained certain effects and the syndrome of kidney and essence deficiency, blood and Qi stasis that treated with strengthening bones and essence, promoting flow of qi and blood as well. So as the syndrome of Yang deficiency of kidney, phlegm and blood stasis resisting meridian. [Conclusion] Ancient and modern physicians have certain effects in the treatment of bone atrophy.They both believe that Qi and blood stasis are the factors which lead to bone atrophy, therefore, activating Qi and blood as treatment of bone atrophy are both agreed.The difference is that the ancient physicians believed that the spleen and stomach deficiency was the key to the formation of bone atrophy.Coordinating Yangming meridian as treatment.Modern physicians believe that kidney deficiency and blood stasis is the key to the formation of bone atrophy.Nourishing kidney and activating blood as treatment mainly.