Quality marker (Q-Marker) is an innovative concept and model for quality control of Traditional Chinese medicines (TCMs), which will navigate the new direction of quality development of TCMs. Yet, how to characterize the overall quality attributes of TCMs and their biological effects is still debating. In view of this key scientific issue, this paper proposes a research method based on mass spectrometry imaging (MSI) technology for the discovery and confirmation of TCMs Q-Marker. MSI is powerful in investigating the spatial distribution of molecules in a variety of samples, and visualizing the information obtained from MS. On this basis, combine with the five principles of TCMs Q-Marker validation, i.e., specificity, transmission and traceability, testability, prescription compatibility, and validity, were applied to confirm the finalized Q-Marker. It will lead the new direction of quality development of TCMs.

Objective To investigate the factors influencing the development of extra-pulmonary tuberculosis(EPTB)in patients with viral hepatitis complicated by pulmonary tuberculosis(PTB).Methods A retrospective analysis was conducted on 427 patients with Hepatitis B Virus(HBV)and Hepatitis C Virus(HCV)infections complicated by PTB admitted to the tuberculosis department of Kunming Third People's Hospital from January 2015 to December 2020.Patients were divided into the EPTB complication group(n=72)and the non-EPTB complication group(n=355)based on the presence of EPTB.Clinical treatment data of patients were collected.Univariate and multivariate Logistic regression analyse were used to screen independent risk factors for EPTB as predictive factors.A nomogram prediction model was established for Extrapulmonary Tuberculosis(EPTB)complications in patients with viral hepatitis and Pulmonary Tuberculosis(PTB),evaluated using the Hosmer-Lemeshow test and ROC curve analysis.Results Among the 427 patients,292(68.3%)were male and 135(31.7%)were female,with 72 cases of EPTB,resulting in an incidence rate of 16.86%.In the EPTB group,there were 34 males(47.2%)and 38 females(52.8%).The types of EPTB included tuberculous pleuritis(21 cases,29%),tuberculous peritonitis(16 cases,22%),lymph node tuberculosis(13 cases,18%),tuberculous encephalitis(5 cases,6%),intestinal tuberculosis(6 cases,8%),bone tuberculosis(5 cases,6%),pelvic tuberculosis(3 cases,4%),and genitourinary tuberculosis(3 cases,4%).Multivariate logistic regression analysis showed that gender(OR=0.425,95%CI:0.250-0.722,P=0.02),low triglyceride(TG)levels(OR=0.837,95%CI:0.717-0.978,P=0.025),the tuberculosis-specific antigen A(ESAT-6)(OR=1.007,95%CI:1.003～1.011 were independent influencing factors for EPTB in patients with PTB complicated by HBV and HCV infections.The optimal cutoff value for the nomogram model is 0.192,with a sensitivity of 0.611,specificity of 0.710,Youden index of 0.741,positive likelihood ratio of 2.103,and negative likelihood ratio of 0.548.The Hosmer-Lemeshow test yielded χ2=2.631,P=0.955.ROC curve analysis showed an AUC of 0.693,95%CI:0.629 1～0.7574.Conclusion The prediction model based on gender,low TG levels and ESAT-6 can well predict the occurrence of EPTB to some extent,providing a reference for clinical treatment.

Objective To evaluate the relationship between nutritional parameters and the risk of venous thromboembolicism(VTE)in patients with tuberculosis so as to identify the risk factors and predictors of thrombosis and assist in the early identification of high-risk factors for VTE in patients with the pulmonary tuberculosis.Methods A total of 323 patients diagnosed with the pulmonary tuberculosis and hospitalized in Kunming Third People's Hospital from August 2021 to August 2023 were collected.According to the VTE risk assessment of non-operative patients,they were divided into the high-risk group and the low-risk group respectively with 116 and 207 in each group.The nutritional indicators with statistically significant differences between the two groups were screened by Lasso regression.Multivariate Logistic regression was used to screen the independent risk factors for high VTE risk in pulmonary tuberculosis patients,and a nomogram prediction model was constructed.The prediction model was evaluated by receiver operating characteristic curve(ROC),calibration curve,decision curve,and influence curve.Results Patients in the high-risk group were significantly older than those in the low-risk group(59 vs.41,P<0.001),hypertension,gender,and Type 2 diabetes did not differ significantly(P values were 0.084,0.724 and 0.488,respectively).9 variables were selected from the inter-group comparison and Lasso regression,including ALB,HCT,NRS2002 scores,HBDH,RDW-SD,RDW-CV,TG,CONUT scores,and NEFA.Multivariate Logistic regression analysis showed that ALB,NRS2002 scores,RDW-SD,and CONUT scores were independent influencing factors for the high risk of VTE scores in patients with tuberculosis(P<0.005).Area under the ROC curve showed that the AUC(0.892)for high-risk VTE scores in patients with the pulmonary tuberculosis was greater than that of ALB(0.803),NRS2002 score(0.735),RDW-SD(0.685),and CONUT score(0.774).Fitting prediction model:Logit(P):Y=0.433×NRS-0.136×ALB+0.411×CONUT score+0.072×RDW-SD-1.770,P=1/(1+e-Y)(Y:prediction index,P:prediction probability).Calibration curve showed that the model prediction tended to be consistent with the actual results(U:>0.05),and the decision curve and influence curve showed that the model can bring clinical benefits.Conclusion ALB,NRS2002 scores,RDW-SD,and CONUT scores are independent influencing factors for the high risk of VTE scores in patients with tuberculosis.They can guide the clinical practice,improve these indicators as soon as possible,reduce VTE scores,and reduce the thrombosis risk.At the same time,the prediction model performs well in the verification cohort,with its discrimination ability,calibration accuracy and clinical utility(decision curve analysis)all reaching a satisfactory level.

Objective Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and network pharmacology technology combined with pharmacodynamic experiments were used to analyze the quality markers(Q-markers)in Saorilao Qingfei Zhike Capsules.Methods Using UPLC-Q-TOF-MS technology,the chemical components in different polar extracts of Saorilao Qingfei Zhike Capsules was analyzed.Potential pharmacological components were screened by using antitussive and expectorant models.The"components-targets-diseases"network was constructed and potential Q-markers were screened by network pharmacology technology.Then we conducted pharmacodynamic validation to confirm the Q-markers,which have antitussive and expectorant effects in Saorilao Qingfei Zhike Capsules.Results A total of 120 compounds were obtained from the Saorilao Qingfei Zhike Capsules through qualitative analysis.Among the extracts of different polarity,44 compounds were derived from petroleum ether extract,85 compounds were derived from ethyl acetate extract,79 compounds were derived from n-butanol extract,and 71 compounds were derived from water extract.The results of pharmacological experiments showed that among extracts of different polarity,petroleum ether extract had the best antitussive effect,while n-butanol extract had the best expectorant effect.Three core components for eliminating phlegm and relieving cough were screened through network pharmacology techniques:farcalinol,farcalinediol,and rubimaillin.Pharmacodynamic studies verified that all core components mentioned above have certain antitussive and expectorant effects.Conclusion Based on the above research,farcalinol,farcalindiol,and rubimaillin can be used as Q-markers for the antitussive and expectorant effects of Saorilao Qingfei Zhike Capsules.This paper provides reference for the quality standard of Saorilao Qingfei Zhike Capsules.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory responses.Orthodontic tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor cells.However,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains unknown.In this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process.Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively.Using Caspase-1-/-mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1.Moreover,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced osteoclastogenesis.Mechanistically,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells.Overall,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.