ObjectiveTo observe the distribution of traditional Chinese medicine （TCM） syndrome types in advanced pancreatic cancer patients， and explore the association between median survival time and different TCM syndromes and different intervention times of Chinese herbal medicine （CHM）. MethodsThe clinical data of 136 advanced pancreatic cancer patients who have received CHM for more than 3 months were collected retrospectively， including gender， age， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， western medicine treatment methods， TCM diagnosis and treatment information， and survival time. The Kaplan-Meier （KM） estimator was used， and the median survival time of patients was calculated. The TCM syndrome type of each patient was judged， and the main single syndrome types and compound syndrome types were summarized. The median survival time was compared among different compound syndrome types. The patients were further divided into the group of those having received CHM ≥6 months and those having received CHM ＜6 months. Whether receiving CHM ≥6 months was taken as the grouping variable， while the matching variables were age， gender， family history， smoking history， drinking history， location of disease， lymph node metastasis， multiple distant metastasis， surgery， chemotherapy， and radiotherapy when propensity score matching was performed， and the difference in median survival time between the two groups of patients before and after matching was compared. ResultsFor 136 cases of advanced pancreatic cancer， the top five single syndromes were spleen qi deficiency， liver blood stasis， liver qi stagnation， spleen dampness， and liver heat. The main compound types were liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， liver constraint， qi stagnation and spleen deficiency syndrome， spleen-stomach yang deficiency and blood stasis syndrome， and spleen deficiency and dampness-heat internal accumulation syndrome. The overall median survival time before and after matching was 12.47 （7.70，17.10） months and 13.77 （8.83，17.20） months， respectively， and was significantly higher in the group treated with CHM ≥ 6 months than that treated with CHM ＜6 months （P＜0.05）. Among the 136 patients before matching， the median survival time of patients with spleen deficiency and dampness-heat internal accumulation syndrome was longest ［16.23 （14.17，19.40） months］， while that of patients with spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［7.33 （5.80，12.83） months］. For patients with liver constraint， spleen deficiency and blood stasis syndrome， liver-gallbladder damp-heat and blood stasis syndrome， and spleen-stomach yang deficiency and blood stasis syndrome， those having received CHM ≥ 6 months have much longer median survival time than those having received CHM ＜6 months （P＜0.05）. Among the 108 patients after matching， the median survival time of those with spleen deficiency and dampness-heat internal accumulation syndrome was the longest ［15.23 （7.67，18.27） months］， while that of spleen-stomach yang deficiency and blood stasis syndrome was the shortest ［8.80 （6.90，16.17） months］. For patients with liver-gallbladder dampness-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome， the median survival time was higher in the group treated with CHM ≥ 6 months treated with CHM ＜6 months （P＜0.05）. ConclusionAfter treatment with CHM， advanced pancreatic cancer patients with spleen deficiency and damp-heat internal accumulation had a better prognosis， while those with spleen-stomach yang deficiency and blood stasis had a worse prognosis. Treatment with CHM ≥ 6 months could extend the median survival of advanced pancreatic cancer patients with liver-gallbladder damp-heat and blood stasis syndrome and spleen-stomach yang deficiency and blood stasis syndrome.

Objective To explore the association of epidermal growth factor receptor(EGFR)mutant non-small cell lung cancer(NSCLC)with tyrosine kinase inhibitor(TKI)-related rash based on network pharmacology and to predict the potential traditional Chinese medicine.Methods Gene chip data of EGFR mutant NSCLC cell lines and normal fibroblasts before and after treatment with erlotinib,a TKI,were collected from Gene Expression Omnibus database.Differentially expressed genes were screened using limma package of R 4.3.2 software.Cross-over target genes were screened using venn package.The differentially expressed genes and cross-over target genes were analyzed using ClusterProfiler package.CoreMine Medical database was used to predict traditional Chinese medicine of the cross-over target genes,and the nature,flavour,and channel tropism were analyzed.The results were verified by molecular docking method.Results A total of 126 cross-over target genes were screened.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the differentially expressed genes and cross-over target genes were enriched in chromosome,spindle and other regions,and were involved in biological processes such as mitosis and DNA replication.These genes were also associated with signaling pathways including DNA replication,lysosomes,and cell cycle.Gene set enrichment analysis results showed that chemokine pathway and nucleotide-binding oligomerization domain-like receptor signaling pathway were activated in the NSCLC cells,and mammalian target of rapamycin signaling pathway and amino acid metabolic pathway were disturbed in the fibroblasts after treatment with erlotinib.CoreMine Medical database predicted that 354 kinds of traditional Chinese medicines were mainly classified as cold,warm and flat,bitter,pungent and sweet,belonging to stomach,lung and liver meridians.Taking Scutellaria baicalensis as an example,molecular docking analysis of experimentally validated target genes and their active components revealed strong binding interactions between the target genes and active components.Conclusion EGFR mutant NSCLC and TKI-related rash have homology in pathogenesis,both involving DNA replication and cell cycle,which provides traditional Chinese medicine medication instruction for patients with EGFR mutant NSCLC and TKI-related rash.

Objective To investigate the application of bronchoscope for children(BF-XP290)in diagnosing and treating peripheral pulmonary lesions(PPL)in adults.Methods Bronchoscope for children(BF-XP290)was used to diagnose and treat PPL.Results BF-XP290 could diagnose and treat PPL in direct view,and other techniques could overcome its shortcomings.Conclusion Bronchoscope for children(BF-XP290)can partially replace radial endobronchial ultra-sound(R-EBUS)in diagnosing and treating PPL in adults,reducing the investment of medical equipment,and is worthy of clinical promotion.

Objective:To summarize the clinical characteristics and genetic features of tyrosine hydroxylase deficiency(THD) caused by TH gene variants for the improvement of the understanding of the disease. Methods:The clinical and genetic data of 33 children with THD caused by TH gene variants were diagnosed in the Department of Neurology of Beijing Children′s Hospital, Capital Medical University from May 2011 to January 2020 and their data were retrospectively collected and analyzed. Results:There were 19 females and 14 males.The age at onset was ranged from 0 to 6.3 years.13 patients developed diseases, accompanied with fever after infection, and 1 patient suffered from hypoxia, 19 patients suffered from no predisposing factors.There were 7 mild TH-deficient dopa-responsive dystonia cases, 16 severe TH-deficient infantile parkinsonism with motor delay cases and 10 very severe TH-deficient progressive infantile encephalopathy cases.Clinical symptoms were fluctuating, including 26 cases of diurnal fluctuation, 22 cases of infection aggravation, and 30 cases of fatigue aggravation.The initial symptoms included tiptoeing and numbness in the limbs(7 cases), motor development retardation or degression (26 cases), fremitus (8 cases), ptosis (2 cases), and status dystonicus (3 cases). Other clinical features had hypermyotonia (23 cases), hypomyotonia (27 cases), decreased movement (27 cases), decreased facial expression (24 cases), fremitus (18 cases), tiptoeing (20 cases), talipes equinovarus (7 cases), ptosis (8 cases), oculogyric crisis (10 cases), salivation (21 cases), dysphagia (12 cases), dysarthria (16 cases), dyspnea (3 cases), increased sleep (10 cases), decreased sleep (5 cases), irritable mood (15 cases), apathetic mood (2 cases), profuse sweating (8 cases), and status dystonicus (6 cases). A total of 6 patients′ right limbs were more severe, and 14 patients′ lower limbs were more severe.Eight patients had family history, and Levodopa treatment was effective for all patients.Ten patients suffered side effects, including dyskinesia and irritability.Four patients were lost follow-up, and 29 patients were followed up between 0.8 and 13.2 years old until Ja-nuary 2020.Totally, 22 patients almost had no such symptoms.Twenty-five TH gene pathogenic variants were discovered in 33 patients.There were 13 novel variants (c.1160T>C, c.1303T>C, c.887G>A, c.1084G>A, c.1097A>T, c.734G>T, c.907C>G, c.588G>T, c.992T>G, c.755G>A, c.184-6C>T, c.1510C>T, c.910G>A) and 2 patients had c. 910G>A variant.Meanwhile, there were 5 hot variants [c.698G>A(13 cases), c.457C>T(9 cases), c.739G>A(6 cases), c.1481C>T(4 cases), c.694C>T(3 cases)]. c.910G>A(2 cases) may be the foun-der variant of Chinese population. Conclusions:THD caused by TH gene variant mostly onsets from infant, with complex clinical features.Most of these patients were severe, and only a few were very severe and mild.Very severe and mild symptoms were easily misdiagnosed.Levodopa treatment was obviously effective.A possible founder variant of Chinese population (c.910G>A) was found.c.698G>A and c. 457C>T mutations mainly appeared in patients with severe and extremely severe THD, while c. 739G>A mainly appeared in patients with mild THD.

OBJECTIVE：To optimize the primary processing technology of Gentiana rigesce ns. METHODS ：HPLC method was adopted for content determination of loganic acid ，swertiamarin and gentiopicroside in G. rigescens ，and overall desirability value （OD value ） of the contents of above 3 components was taken as index to carry out single factor test on blanching temperature，blanching time and drying temperature. Based on that ，Box-Behnken design-response surface methodology was used to optimize primary processing technology of G. rigescens . Validation test was also performed. The samples prepared by optimized technology were compared with those dried in the shade. RESULTS ：The optimal primary processing technology of G. rigescens included blanching time of 5 min，blanching temperature of 40 ℃ and drying temperature of 60 ℃. Validation test showed that the average OD value of the 3 components was 0.565 2，with a deviation of 0.94％ from the predicted value （0.570 6）. Compared with samples dried in the shade ，OD value of 3 components in samples prepared by optimized technology were increased significantly ， indicating the quality of the samples prepared by the optimized technology was better. CONCLUSIONS ：The optimal technology is stable and feasible ，and can be used for the primary processing of G. rigescens .

Objective To investigate the expression and clinical significance of Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in serum and cerebrospinal fluid (CSF) of patients with severe hand, foot and mouth disease (HFMD). Methods Ninety children with HFMD were classified into three groups with 30 in each group:critical group (clinical stage 3), severe group (clinical stage 2) and common group (clinical stage 1, excluding encephalitis with CSF and other examinations). Another thirty healthy children were randomly selected as the control group. The levels of BNIP3 in serum and CSF were detected before and after treatment. Moreover, serum neuro-specific enolase ( NSE) and S100B protein were also measured to analyze their correlation with BNIP3. Receiver operating characteristic ( ROC) curve was used to evaluate the prediction efficiency of BNIP3 for the severity of HFMD. Results The levels of serum BNIP3, S100B protein and NSE in the critical group were higher than those in the other three groups ( P<0. 01). CSF BNIP3 level in the critical group were significantly higher than that in the common and severe groups (P<0. 01). Serum BNIP3, S100B protein and NSE were significantly higher in the severe group than in common and control groups (P<0. 01). CSF BNIP3 was significantly increased in the severe group as compared with that in the common group (P<0. 01). After treatment, the levels of BNIP3, S100B protein and NSE in serum and BNIP3 in CSF were decreased in both critical and severe groups (P<0. 01). The lev-els of BNIP3 in serum and CSF were positively correlated with the level of S100B protein and NSE ( P<0. 01). Serum BNIP3 had the highest Youden value at the cut-off value of 3. 015μg/L, with a sensitivity of 83. 33％ and a specificity of 90. 00％, in the prediction of severe HFMD. CSF BNIP3 had the highest Youden value at the cut-off value of 1. 735 μg/L, with a sensitivity of 73. 33％ and a specificity of 93.33％, in the prediction of severe HFMD. Conclusions BNIP3 is involved in the pathological process of brain injury in children with severe HFMD. Detection of BNIP3 helps evaluate the severity and prognosis of HFMD.

Objective: To investigate the expression and clinical significance of Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in serum and cerebrospinal fluid (CSF) of patients with severe hand, foot and mouth disease (HFMD). Methods: Ninety children with HFMD were classified into three groups with 30 in each group: critical group (clinical stage 3), severe group (clinical stage 2) and common group (clinical stage 1, excluding encephalitis with CSF and other examinations). Another thirty healthy children were randomly selected as the control group. The levels of BNIP3 in serum and CSF were detected before and after treatment. Moreover, serum neuro-specific enolase (NSE) and S100B protein were also measured to analyze their correlation with BNIP3. Receiver operating characteristic (ROC) curve was used to evaluate the prediction efficiency of BNIP3 for the severity of HFMD. Results: The levels of serum BNIP3, S100B protein and NSE in the critical group were higher than those in the other three groups (P<0.01). CSF BNIP3 level in the critical group were significantly higher than that in the common and severe groups (P<0.01). Serum BNIP3, S100B protein and NSE were significantly higher in the severe group than in common and control groups (P<0.01). CSF BNIP3 was significantly increased in the severe group as compared with that in the common group (P<0.01). After treatment, the levels of BNIP3, S100B protein and NSE in serum and BNIP3 in CSF were decreased in both critical and severe groups (P<0.01). The levels of BNIP3 in serum and CSF were positively correlated with the level of S100B protein and NSE (P<0.01). Serum BNIP3 had the highest Youden value at the cut-off value of 3.015 μg/L, with a sensitivity of 83.33% and a specificity of 90.00%, in the prediction of severe HFMD. CSF BNIP3 had the highest Youden value at the cut-off value of 1.735 μg/L, with a sensitivity of 73.33% and a specificity of 93.33%, in the prediction of severe HFMD. Conclusions BNIP3 is involved in the pathological process of brain injury in children with severe HFMD. Detection of BNIP3 helps evaluate the severity and prognosis of HFMD.

Objective To evaluate the short-term efficacy,safety and impact on the quality of life of anlotinib in third-line and above treatment for advanced non-small cell lung cancer (NSCLC) patients.Methods All the patients received alotinib 12 mg/d.One cycle was defined as 2 weeks on-treatment followed by 1 week off-treatment until disease progression or treatment intolerance.Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to assess tumor responses.Common Terminology Criteria for Adverse Events (CTCAE) 4.02 was used to assess the adverse events.The European Organization for Research on Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13 were used to assess quality of life.Results Among 27 patients in study,no complete response (CR) was found,2 patients (7.4％) achieved partial response (PR),16 patients (59.3％) achieved stable disease (SD),9 patients (33.3％) achieved progressive disease (PD),objective response rate (ORR) was 7.4％,and disease control rate (DCR) was 66.7％.The scores of physical functioning (76.00 ± 10.55 vs.64.44 ± 11.59),emotional functioning (81.67 ± 8.71 vs.76.11 ±6.71) and global health status (48.87 ±7.97 vs.40.56 ± 12.49) of the QLQ-C30 scale after treatment were higher than those before treatment,with statistically significant differences (t =-4.516,P ＜0.001;t=-2.646,P=0.019;t=-3.872,P=0.002).Fatigue (50.37±8.95 vs.40.74±13.86),nausea and vomiting (26.54 ± 16.18 vs.14.20 ± 11.97),loss of appetite [M(QR):33.33 (33.33) vs.33(33.33)] were better than before (t =-2.476,P =0.027;t =-5.036,P ＜0.001;Z =-2.923,P =0.003);pain (28.88 ± 14.23 vs.33.33 ± 13.60) and dyspnea [33.33 (33.33) vs.33.33 (66.67)] scores were lower than before (t =3.674,P =0.003;Z =-3.266,P =0.001).The scores of cough (24.44 ±19.12 vs.45.24 ±20.34),shortness of breath [11.11(22.22) vs.33.33(22.22)] and chest pain [0.00(33.33)vs.33.33 (33.33)] in the QLQ-LC13 scale after treatment were lower than those before treatment,with statistically significant differences (t =4.000,P =0.001;Z =-4.125,P ＜0.001;Z =-1.890,P =0.034);the scores of sore mouth or tongue [0.00(33.33) vs.0.00(0.00)] and hands and feet tingling [33.33(33.33) vs.0.00(0.00)] were higher than before (Z=-2.000,P=0.046;Z=-2.264,P=0.024).Common adverse reactions included hypertension,fatigue,elevated thyroid stimulating hormone,proteinuria,hand-foot syndrome,oral mucositis,hemoptysis,etc,mainly grade 1-2,and they were all improved after the treatments.Conclusion Anlotinib as a third-line and further therapy is positive effected and well tolerated.It can alleviate the clinical symptoms and significantly improve the quality of life of NSCLC patients.

Objective: To investigate the clinical features, laboratory characteristics and genetic diagnosis of Kabuki syndrome (KS). Methods: Between September 2014 and September 2016, seven children with clinically diagnosed KS from the neurology department, Beijing Children Hospital, Capital Medical University were included in this study. Three of them were male and 4 were female aged from 19 days to 6 years and 4 months with a median age of 3 years and 1 month. The clinical features, laboratory and imaging materials, gene tests were analyzed prospectively. Results: Clinical manifestation: cephalofacial anomaly: all seven cases had unusual facies presented as long palpebral fissures, eversion of the lateral third of lower eyelids, arched eyebrow with brow sparse, epicanthus, orbital hypertelorism, short columella with broad and depressed nasal tip; six cases presented with palatal arch deformity; four cases presented with ptosis; three cases presented with dental abnormalities and hearing impairment respectively; two cases presented with strabismus and earlap malformation respectively; one case presented with amblyopia. Six cases presented with skeletal anomalies. Six cases presented with dermatoglyphic anomalies. All cases presented with mild to moderate mental retardation. Three cases presented with short stature. Four cases presented with cardiac abnormalities. Three cases presented with epileptic seizures. Others: three cases presented with dystonia and neonatal hyperbilirubinemia respectively; two cases presented with feeding problem and hypoglycemia respectively; one case presented with micropenis and fetal finger pads respectively. All seven patients received magnetic resonance imaging (MRI) tests, and none demonstrated an abnormal finding. Five patients received electroencephalogram (EEG) tests, and three of them presented with seizures and EEG abnormalities. Five patients received genetic testing and all presented with KMT2D heterozygous mutations which were new mutations proved by parents validation (three cases were nonsense mutations, one was frameshift mutation, one was missense mutation). All patients received rehabilitation training and symptomatic treatments. Three patients presented with epileptic seizures received antiepileptic therapy. At a median follow-up of 11 months (from 4 months to 2 years), one patient died, one lost to follow-up and five had improved intellectual and physical development. Epileptic seizures were controlled or reduced significantly in three patients presented with epileptic seizures. Conclusions KS is a multisystem disease with complicated manifestations, which needs a combination of various diagnosis and treatments. Genetic testing can help determine the diagnosis. Unusual facies and mental retardation are the main clinical features and diagnostic clue. It is important to improve prognosis through increasing the knowledge of KS, early diagnosis, and treatment.

Objective To investigate the clinical application effects of gabapentin in the treatment of recurrent trigeminal neuralgia.Methods 68 patients with recurrent trigeminal neuralgia were chosen as study subjects,and they were divided into control group and research group according to the digital table.The research group was treated with gabapentin,the control group was treated with carbamazepine.After treatment for 4 weeks,the clinical effects,life satisfactory index,pain,drug dosage and adverse reaction between the two group were compared.Results Each group had 32 patients completed the study.The total effective rate of the research group was higher than that of the control group(68.75％ vs.59.37％),the difference was not statistically significant(x2 =0.611,P ＜0.05).The average gabapentin dosage in the research group was higher than the average carbamazepine dosage in the control group,the difference was statistically significant (t =11.278,P ＜ 0.05).Before treatment,the VAS scores between the two groups had no statistically significant difference (t =0.153,P ＞ 0.05).At 7 d after treatment,the VAS scores in the research group was lower than that in the control group [(4.09 ± 0.83) points vs.(4.63 ± 0.79) points],the difference was statistically significant (t =2.666,P ＜ 0.05).At 14 d and 28 d after treatment,the VAS scores between the two groups had no statistically significant difference (t =1.527,0.352,all P ＞ 0.05).Before treatment and 7 d after treatment,the life satisfaction index B (LSI-B) scores between the two groups had no statistically significant difference(t =0.049,0.224,all P ＞ 0.05).At 14 d and 28 d after treatment,LSI-B scores in the two groups were both increased,which in the research group was higher than taht in the control group[14 d:(15.09 ± 3.68) points vs.(12.91 ± 3.45) points,28 d:(16.48 ± 3.43) points vs.(13.35 ± 3.14) points],the differences were statistically different(t =2.445,3.808,all P ＜ 0.05).The incidence rate of adverse reaction of the research group was lower than that of the control group(15.63％ vs.37.50％),the difference was statistically significant (x2 =3.925,P ＜ 0.05).Conclusion Gabapentin has similar treatment effects in recurrent trigeminal neuralgia as carbamazepin,and gabapentin has better improvement in patients'life quality,and with better safety.