ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

OBJECTIVE To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample. METHODS The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode. RESULTS There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids. CONCLUSION The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.

Objective: To investigate the hygienic status of the central air conditioner ventilation system in public places in urban areas of Ma'anshan City, Anhui Province, so as to provide insights into formulation of supervision and management interventions. Methods: A total of 15 public places with the central air conditioner ventilation system were randomly sampled from main urban areas in Ma'anshan City in 2022. Sampling and detection were performed following the standard GB/T 18204.5—2013 Examination methods for public places Part 5: Central air conditioning ventilation system, including total number of bacteria and total number of fungus on the inner surface of wind pipes, total number of bacteria and fungus, particulate matter (PM10) and β-hemolytic streptococci in the air supply system, and Legionella pneumophila in the cooling water, and the detection indicators were assessed following the WS 394—2012 Guideline for hygiene of the central air conditioner ventilation system in public places. The eligible rate of samples, the detection rate of L. pneumophila were analyzed. Results: A total of 368 samples were collected from 15 public places, and the qualified rate was 50.54%, no places had all eligible measurement indicators. The qualified rates of total bacteria and fungus numbers on the inner surface of wind pipes were 52.67% and 59.33%. The qualified rates of total bacterium number, total fungus number, PM10 and β-hemolytic streptococci were 12.00%, 28.00%, 90.00% and 96.00% in the air supply system. The qualified rates of samples in administrative workplaces, hotels, bathing places and malls (supermarkets) were 32.50%, 59.24%, 61.09% and 68.92%, the qualified rates of total bacteria on the inner surface of air ducts were 8.33%, 72.46%, 66.67% and 61.90%, and the qualified rates of total fungus numbers in air supply were 0, 21.70%, 33.30% and 71.40%, respectively, with statistical significance (P<0.05). A total of 18 cooling water samples were collected, and L. pneumophila was detected in three samples (16.67%). Conclusions Poor hygiene is seen in the central air conditioning ventilation systems in public places in main urban areas of Ma'anshan City. High attention needs to be paid to contamination of bacterium, fungus and L. pneumophila, and expansion of supervision coverage and improved supervision intensity are recommended.

Pulmonary sarcomatoid carcinoma(PSC)is a rare and highly malignant tumor,which includes the follow-ing five pathologic types:pleomorphic carcinoma,spindle cell carcinoma,giant cell carcinoma,carcinosarcoma and pulmonary blastoma.The onset of PSC is occult with non-specific clinical symptoms and signs.The clinical manifestations include irritat-ing cough,bloody sputum,dyspnea,chest pain and so on,which are closely related to the growth and invasion site of the tumor.PSC tends to metastasize early,so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit.A patient with primary PSC which led to 90%stenosis in central airway was treated by com-bined method of vascular and tracheoscopic intervention in our respiratory center.This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery.Herein we report the case for clinical reference.

Background and objective As a new technique developed in recent years,bronchoscopic interven-tion therapy has the advantages of minimal invasion,high safety and repeatability.The aim of this study is to investigate the clinical characteristics of bronchopleural fistula(BPF)induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF,so as to provide support for prevention and treatment of BPF.Methods Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Cen-ter of Dongzhimen Hospital,Beijing University of Chinese Medicine from June 2020 to September 2023 were collected.Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol,combined with blocking therapy with N-butyl cyanoacrylate,medical bioprotein glue or silicone prosthesis.Patients with fistula diameter＞5 mm were im-planted with different stents and cardiac occluders.Locations and characteristics of fistulas were summarized,meanwhile,data including Karnofsky performance status(KPS),shortbreath scale(SS),body temperature,pleural drainage volume and white blood cell count before and after operation were observed.Results For all 64 patients,96 anatomic lung resections in-cluding pneumonectomy,lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations.The proportion of fistula in the right lung(63.5％)was significantly higher than that in the left(36.5％).Besides,the right inferior lobar bronchial fistula was the most common(40.5％).After operation,KPS was significantly increased,while SS,body tem-perature,pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values(P＜0.05).By telephone follow-up or readmission during 1 month to 38 months after treament,median survival time was 21 months.33 patients(51.6％)showed complete response,7 patients(10.9％)showed complete clinical response,18 patients(28.1％)showed partial response,and 6 patients(9.4％)showed no response.As a whole,the total effective rate of broncho-scopic intervention for BPF was 90.6％.Conclusion BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating.Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

Pulmonary mixed squamous cell and glandular papilloma(MSCGP)is a subtype of pulmonary papil-loma,which can be classified as central type and peripheral type based on its site of development.The central type is the most common.The clinical manifestations of pulmonary MSCGP are mainly related to the location of the tumor.Surgery is the main treatment for this disease.Bronchoscopic interventional treatment for the MSCGP in the central trachea could receive satis-factory effect.We reported a patient suffered from diffuse tracheal MSCGP who was treated by bronchoscopic interventional treatment in Respiratory Disease Center,Dongzhimen Hospital of Beijing University of Chinese Medicine,aiming to enhance the recognition of the clinical features and provide clinical references for the diagnosis and treatment of such disease.

ObjectiveBased on non-targeted metabolomics， to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus（T2DM） rats by Fuling Yunhua granules， and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats， half male and half female， were randomly divided into the control group， model group， and high， medium， low dose groups of Fuling Yunhua granules（20.70， 10.35， 5.18 g·kg^-1 in raw drug amount） and the positive drug group（pioglitazone hydrochloride tablets， 8.1 mg·kg^-1）. Except for the control group， other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin（STZ） to establish a T2DM rat model. After successful modeling， the treatment groups were administered the corresponding drugs by gavage， and the control group and model group were treated with an equal volume of saline by gavage， once/d， for 28 d. Fasting blood glucose（FBG） and glycosylated hemoglobin A1c（GHbA1c） levels were measured in all groups of rats during the administration period， and hematoxylin-eosin（HE） staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-LTQ-Orbitrap MS）， and the data were processed using principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential metabolites were identified by the Human Metabolome Database（HMDB） and the Kyoto Encyclopedia of Genes and Genomes（KEGG）， and screened for differential metabolites with variable importance in the projection（VIP） value>1， P<0.05， and fold change（FC）<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0， then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic（ROC） curves. ResultCompared with the control group， the FBG level of rats in the model group increased significantly（P<0.01）， the GHbA1c content tended to increase， but the difference was not statistically significant， and the pancreatic tissue of rats was obviously damaged， the number of pancreatic islets decreased， and the pancreatic β-cells were obviously reduced， atrophied and enlarged. Compared with the model group， the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration（P<0.05， P<0.01）， the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced（P<0.05）， and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid， D-amino acid metabolism， steroid hormone biosynthesis， and glycerophospholipid metabolism in rats. Compared with the model group， the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted， and the pathway enrichment analysis found that D-amino acid metabolism， retinol metabolism， glycine， serine and threonine metabolism， tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol， D-piperidinic acid， D-serine， and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.