ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveTo investigate the processing technology of calcined Haematitum based on the concept of quality by design（QbD） and to assess its health risk. MethodsTaking whole iron content， Fe²⁺ dissolution content and looseness as critical quality attributes（CQAs）， and calcination temperature， calcination time， spreading thickness and particle size as critical process parameters（CPPs） determined by the failure mode and effect analysis（FMEA）， the processing technology of calcined Haematitum was optimized by orthogonal test combined with analytic hierarchy process-criteria importance through intercriteria correlation（AHP-CRITIC） hybrid weighting method. The contents of heavy metals and harmful elements were determined by inductively coupled plasma mass spectrometry， and the health risk assessment was carried out by daily exposure（EXP）， target hazard quotient（THQ） and lifetime cancer risk（LCR）， and the theoretical value of the maximum limit was deduced. ResultsThe optimal processing technology for calcined Haematitum was calcination at 650 ℃， calcination time of 1 h， particle size of 0.2-0.5 cm， spreading thickness of 1 cm， and vinegar quenching for 1 time［Haematitum-vinegar（10：3）］. The contents of 5 heavy metals and harmful elements in 13 batches of calcined Haematitum were all decreased with reductions of up to 5-fold. The cumulative THQ of 2 batches of samples was>1， while the cumulative THQ of all batches of Haematitum was>1. The LCR of As in 1 batches of Haematitum was 1×10^-6-1×10^-4， and the LCR of the rest was<1×10^-6， and the LCRs of calcined Haematitum were all<1×10^-6， indicating that the carcinogenic risk of calcined Haematitum was low， but special attention should still be paid to Haematitum medicinal materials. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg were formulated as 1 014， 25， 17， 27， 7 mg·kg^-1. ConclusionThe optimized processing technology of calcined Haematitum is stable and feasible， and the contents of heavy metals and harmful elements are reduced after processing. Preliminary theoretical values of the maximum limits of Cu， As， Cd， Pb and Hg are formulated to provide a scientific basis for the formulation of standards for the limits of harmful elements in Haematitum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

Objective To summarize the potential risk factors that may arise in the national drug sampling and testing inspection process in recent years,to focuse on the operation of the quality management system,and to put forward proposals on how to do a good job under the new drug regulatory model of sampling and testing work.Methods Focusing on the investigation of data integrity and authenticity,the analysis focuses on the analysis of risk points such as reagent management,standard substance management,instrument,and facility management,electronic data management and other issues,and carries out a comprehensive verification of the effectiveness of the operation of the quality management system and so on.Results National drug sampling and testing institutes should strengthen the overall quality management,according to the operation of the laboratory,combined with their respective risk characteristics,reagent management,standard substance management,instrument and facility management,electronic data management and other aspects of the risk of systematic sorting and the establishment of the risk alert function,the development of risk warning lists,and the implementation of the corresponding risk control strategy.Conclusion National drug sampling and testing institutes must strengthen the operation of the process of influencing factors in the effective control of the emphasis on the testing of the work of the key control points and continue to standardize and improve the inspection process of the quality system to ensure that the quality of the various activities in a controlled state.

Objective To investigate the protective effect of cerebrospinal fluid(CSF)on the spinal cord in patients with scoliosis and evaluate its buffering effect during gravitational traction surgery and in daily life,so as to provide a theoretical guidance for surgical planning and postoperative rehabilitation of scoliosis.Methods A three-dimensional coupled spinal cord-CSF finite element model was established to simulate the biomechanical responses of the spine under two scenarios:gravitational traction surgery and daily life.Comparative analyses were conducted for conditions with and without CSF,and the buffering effect of CSF was quantitatively assessed.Results During simulated gravitational traction surgery,CSF significantly reduced the stress and deformation of the spinal cord,with the stress in spinal cord white and gray matter decreasing by 65％-90％and deformation decreasing by 70％-95％.In the daily life scenario,CSF provided greater protective effects in lateral flexion and anterior-posterior flexion directions,with stress reductions of 60％-85％.However,in torsion,the buffering effect of CSF was relatively weaker,with stress reductions of only 10％-25％.Conclusions CSF significantly reduces spinal cord stress and deformation during gravitational traction surgery and in daily life,reducing the risk of injury.

Objective To investigate the protective effect of cerebrospinal fluid(CSF)on the spinal cord in patients with scoliosis and evaluate its buffering effect during gravitational traction surgery and in daily life,so as to provide a theoretical guidance for surgical planning and postoperative rehabilitation of scoliosis.Methods A three-dimensional coupled spinal cord-CSF finite element model was established to simulate the biomechanical responses of the spine under two scenarios:gravitational traction surgery and daily life.Comparative analyses were conducted for conditions with and without CSF,and the buffering effect of CSF was quantitatively assessed.Results During simulated gravitational traction surgery,CSF significantly reduced the stress and deformation of the spinal cord,with the stress in spinal cord white and gray matter decreasing by 65％-90％and deformation decreasing by 70％-95％.In the daily life scenario,CSF provided greater protective effects in lateral flexion and anterior-posterior flexion directions,with stress reductions of 60％-85％.However,in torsion,the buffering effect of CSF was relatively weaker,with stress reductions of only 10％-25％.Conclusions CSF significantly reduces spinal cord stress and deformation during gravitational traction surgery and in daily life,reducing the risk of injury.

Bladder-preserving treatment has become a research focus due to its potential to balance therapeutic efficacy and quality of life.In recent years,the rapid development of immunotherapy has brought new opportunities for bladder-sparing strategies.In high-risk non-muscle invasive bladder cancer(HR-NMIBC),emerging regimens such as bacillus calmette-guérin-based immunoenhancement,immuno-chemotherapy combinations,targeted therapy,and gene therapy have demonstrated encouraging efficacy and safety in trials like GU-123 and TRUCE-02,with complete remission rate ranging from 42％-100％.In muscle-invasive bladder cancer(MIBC),immunotherapy is being integrated with trimodal therapy,radiotherapy,chemotherapy,and antibody-drug conjugates,as evidenced by studies such as ReBirth and BTCRC-GU15-023,which reported significant improvements in bladder-intact event-free survival,progression-free survival,and complete remission rate.This review summarizes the latest advances in immunotherapy-based bladder-preserving strategies for both HR-NMIBC and MIBC,aiming to provide insights for future individualized treatment approaches.

Objective To determine the related substances in ornidazole active pharmaceutical ingredient(API)and injections using high performance liquid chromatography(HPLC)and to study the impurity profile of ornidazole using liquid chromatography-tandem mass spectrometry(LC-MS/MS)combined with forced degradation tests,aiming to clarify the sources of impurities and their correlation with the prescription and production process and providing technical support for the unified evaluation and quality control of this product.Methods A Phenomenex Luna C18column(4.6 mm×250 mm,5 μm)was used for the separation of ornidazole and its impurities,with 0.000 5%formic acid as mobile phase A and methanol as mobile phase B under gradient elution.The impurity content of 4 batches of APIs,3 batches of reference preparations,and 11 batches of domestic generic preparations were determined.The structure of unknown impurities was predicted using Jet Stream Ion Focusing Electrospray Ionization-Time of Flight Mass Spectrometry(AJS-TOF-MS/MS),and the sources of impurities were identified combined with forced degradation experiments,the prescription and the production process of various manufacturers.Results Ornidazole and its known impurities were well separated under the chromatographic conditions.The structures of five unknown impurities were inferred,and the sources of the impurities were identified.Conclusion This study provides a reference for impurity analysis,quality control,and overall evaluation of ornidazole API and injection.

Objective To identify potential quality risks of Xiaoer Huatan Zhike Granules(Pediatric Phlegm-Resolving and Cough-Relieving Granules)through National Drug Sampling and Inspection,evaluate their overall quality,and propose improvements to the quality standards.Methods Samples from 34 manufacturers were tested using official standards.Exploratory methods were developed to enhance risk analysis,including thin-layer chromatography(TLC)identification,content uniformity testing,quantitative assays,and screening for unauthorized additives(e.g.,colorants).Results All batches met the official standards(100.0%compliance rate).However,deficiencies were observed:most manufacturers lacked controls for ephedrine hydrochloride content uniformity and quantification,omitted key ingredient identifications(e.g.,herbal components),and exhibited insufficient TLC specificity(e.g.,TLC of Ipecac tincture showed only one spot instead of multiple alkaloid-specific spots).Exploratory studies revealed risks in total emetine/cephaeline content,morroniside A/platycodin D content,ephedrine hydrochloride uniformity,and unauthorized colorant addition.Conclusions The overall quality of this variety is good,but the enterprise should improve the quality control measures throughout the entire process and establish stricter internal control standards;The official standards,unchanged for approximately 30 years,fail to address current regulatory requirements.The statutory quality standards need to be revised and improved.Qualitative or quantitative indicators for all drug flavors in the prescription should be added,and the content uniformity inspection of ephedrine hydrochloride should be increased.