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.

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 investigate the safety and effectiveness of the clinical application of minimally invasive transcatheter patent foramen ovale occlusion.Methods:A total of 123 patients who underwent transcatheter patent foramen ovale (PFO) occlusion at the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 1, 2023, to December 31, 2023, were retrospectively analyzed. According to the surgical protocol, this study divided the patients into the conventional occlusion group (Group A, 53 cases) and the minimal invasive occlusion group (Group B, 70 cases). The patients were followed up for at least six months after surgery to evaluate the safety and effectiveness of the new method.Results:The surgical success rate was 100% in both groups. Intraoperative fluoroscopy time decreased by over 50% (7 min in group A and 3 min in group B, P<0.001). At the six-month postoperative follow-up, contrast-enhanced transcranial Doppler ultrasound sonography revealed seven positive results, two of which indicated large shunts. It was further reviewed for combined pulmonary arteriovenous fistula. One patient experienced a recurrence of stroke after the surgery. The patients' overall migraine and transient ischemia attack (TIA) were significantly relieved, and their overall VAS scores decreased significantly compared to the previous ones. Conclusion:The minimally invasive transcatheter PFO occlusion procedure is safe, reliable, and cost-effective. It warrants further follow-up and promotion. Meanwhile, transcatheter PFO occlusion is an effective treatment for preventing recurrent stroke and relieving symptoms like migraine and TIA in patients.

Objective:To study the risk factors for acute kidney injury (AKI) following one-stage revision surgery combined with intra-articular antibiotics infusion for periprosthetic joint infection (PJI) of the hip joint.Methods:A retrospective analysis was conducted on the data of 168 patients with hip PJI who underwent one-stage revision surgery combined with intra-articular antibiotics infusion in the Department of Joint Surgery, the First Affiliated Hospital of Xinjiang Medical University, from May 1, 2010 to April 30, 2024. There were 87 males and 81 females with an average age of 60.1±14.6 years (range: 21-89 years). The body mass index (BMI) was 24.9±4.6 kg/m 2 (range: 17-41 kg/m 2). PJI was diagnosed according to the criteria of Musculoskeletal Infection Society (MSIS) in 2011. AKI was diagnosed and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. For AKI group and non-AKI group, risk factors were screened by univariate analysis on their age, gender, BMI, BMI≥30 kg/m 2 (yes/no), American Society of Anesthesiologists (ASA) score (II/III), hypertension, diabetes, chronic kidney disease (CKD), surgical side (left/right), duration of intravenous antibiotic use, duration of intra-articular antibiotic use, preoperative blood transfusion, postoperative blood transfusion, baseline hemoglobin value, anemia grade (none/mild/moderate), baseline serum creatinine value, baseline serum creatinine grade (normal/below normal range/above normal range). Variables with P<0.10 were included in the multivariate logistic regression model to identify independent risk factors. Results:The overall incidence of AKI was 9.52%(16/168), among which 50%(8 cases) were stage I AKI, transient and requiring no special treatment. 12.5% (2 cases) were stage II AKI and did not undergo dialysis. 37.5%(6 cases) were stage III AKI. One case needed temporary hemodialysis, and there was no patient requiring long-term dialysis. There were significant differences in age, diabetes, chronic kidney disease and ASA score between AKI group and non-AKI group ( P<0.05). The univariate logistic regression analysis revealed that there were significant differences in age ( P=0.005), BMI ( P=0.078), ASA score level Ⅲ ( P=0.037), diabetes ( P=0.025), CKD ( P=0.003), and low baseline serum creatinine level ( P=0.056). Multivariate logistic regression analysis showed that age, CKD and low baseline serum creatinine level were independent risk factors for AKI ( P<0.05). Conclusions:The incidence of AKI after one-stage revision surgery combined with local antibiotic use in the joint cavity was relatively low in the treatment of PJI after total hip arthroplasty. Hower elderly patients with a history of CKD, or a low baseline serum creatinine level before surgery were at higher risk of developing AKI.

Objective:To investigate the effects and mechanism of metformin on the proliferation and expression of fibrotic proteins of human hypertrophic scar (HS) fibroblasts (Fbs).Methods:The study was an experimental study. From June 2021 to June 2022, 5 patients with HS were admitted to the Department of Burns and Cutaneous Surgery of the First Affiliated Hospital of Air Force Medical University, including 3 males and 2 females, aged from 21 to 36 years. HS tissue was collected, Fbs were isolated and cultured, and Fbs of passage 5 to 7 were used for experiment. Fbs were taken and cultured in their respective media supplemented with phosphate buffered solution (PBS) or metformin at final molarities of 5, 10, 20, and 40 mmol/L for 48 hours. The cell proliferation activity was detected using the cell counting kit-8 (CCK-8), and the proliferation inhibition rate of cells was calculated. The content of hydroxyproline in the cell culture supernatant was measured using a hydroxyproline assay kit. The phosphorylation levels of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in the cells were detected by Western blotting, and the ratios of phosphorylated Akt (p-Akt) to Akt and phosphorylated mTOR (p-mTOR) to mTOR were calculated. After 24 hours of culture, the mRNA expressions of type Ⅰ collagen, type Ⅲ collagen, and α-smooth muscle actin (α-SMA) in the cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction. Another batch of Fbs were divided into control group (with conventional culture), LY294002 group, metformin group, and LY294002+metformin group. LY294002, metformin, and LY294002+metformin were added to the culture media of the last three groups, respectively, with the final molarities of LY294002 and metformin being 20 μmol/L and 10 mmol/L, respectively. CCK-8 was used to detect the cell proliferation activity at 0 (immediately), 24, and 48 hours of culture. After 48 hours of culture, Western blotting was used to detect the phosphorylation levels of Akt and mTOR in the cells, and the ratios of p-Akt to Akt and p-mTOR to mTOR were calculated. The sample size for the cell proliferation inhibition rate experiment was 4, and the sample size for the other experiments was 3.Results:After 48 hours of culture, compared with the cells treated with PBS, the proliferation inhibition rates of the cells treated with 5, 10, 20, and 40 mmol/L metformin were significantly increased (with t values of 10.69, 14.20, 19.73, and 52.54, respectively, P<0.05), the content of hydroxyproline in the culture supernatants of the cells treated with 10, 20, and 40 mmol/L metformin was significantly decreased (with t values of 8.06, 7.86, and 10.25, respectively, P<0.05), and the ratios of p-Akt to Akt in the cells treated with 10, 20, and 40 mmol/L metformin and the ratios of p-mTOR to mTOR in the cells treated with 20 and 40 mmol/L metformin were significantly decreased (with t values of 2.82, 4.28, 9.88, 5.66, and 9.08, respectively, P<0.05). After 24 hours of culture, compared with those treated with PBS, the mRNA expressions of type Ⅰ collagen and α-SMA in the cells treated with 5, 10, 20, and 40 mmol/L metformin and the mRNA expressions of type Ⅲ collagen in the cells treated with 10, 20, and 40 mmol/L metformin were significantly decreased (with t values of 4.35, 8.53, 9.57, 14.77, 4.14, 5.58, 7.89, 9.37, 5.18, 6.85, and 9.15, respectively, P<0.05). At 24 and 48 hours of culture, the proliferation activities of the cells in LY294002 group (with t values of 6.30 and 13.60, respectively) and metformin group (with t values of 6.47 and 10.69, respectively) were significantly lower than those in control group ( P<0.05). After 48 hours of culture, the ratios of p-Akt to Akt in the cells of LY294002 group and metformin group were 0.554±0.027 and 0.681±0.029, respectively, which were significantly lower than 1.053±0.193 in control group (with t values of 4.45 and 3.31, respectively, P<0.05). The ratio of p-Akt to Akt in the cells of LY294002+metformin group was 0.387±0.023, which was significantly lower than that in metformin group ( t=5.95, P<0.05). After 48 hours of culture, the ratio of p-mTOR to mTOR in the cells of LY294002 group was significantly lower than that in control group ( t=4.01, P<0.05), and the ratio of p-mTOR to mTOR in the cells of LY294002+metformin group was significantly lower than that in metformin group ( t=6.05, P<0.05). Conclusions:Metformin can inhibit the proliferation and expression of fibrotic proteins type Ⅰ collagen, type Ⅲ collagen, and α-SMA of human HS Fbs through phosphatidylinositol 3-kinase/Akt/mTOR signaling pathway.

The construction of the National Medical Center and the National Regional Medical Center in the Chengdu-Chongqing Economic Circle (referred to as the dual medical center construction) faces the challenges of insufficient integration of industry, academia, research, and medicine, as well as limited joint development and sharing of high-quality resources. It is urgent to promote the integration and coordinated development of regional education and technology talent resources through the integration of higher medical education, and to enhance the "four chains" synergy with the integration of industry and education as the core, thereby promoting the dual medical center construction. This study investigated and summarized the key issues in the dual medical center construction and the integration of higher medical education in the Chengdu-Chongqing Economic Circle. Based on the theoretical framework of four chain coordination (industry chain-talent chain-education chain-city chain), this study clarified the mechanisms by which integrated higher medical education can promote dual medical center construction. The study found that the integration of higher medical education can effectively promote the optimization of resources for dual medical center construction by constructing a collaborative mechanism of "industry education integration-joint talent cultivation-coordinated discipline construction-intercity cooperation". Based on the strengths in higher education resources in Chengdu and Chongqing, a five-dimension collaborative path was proposed: integrated development; technological leadership; talent oriented; government guidance; and market assistance. The research conclusion not only enhances the understanding of the integration of higher medical education, but also provides theoretical basis and practical reference for the dual medical center construction in the Chengdu-Chongqing Economic Circle. The proposed coordinated development also has reference value for the construction of medical centers in urban agglomerations such as the Beijing-Tianjin-Hebei Urban Agglomeration and the Yangtze River Delta.

Objective:To study the risk factors for acute kidney injury (AKI) following one-stage revision surgery combined with intra-articular antibiotics infusion for periprosthetic joint infection (PJI) of the hip joint.Methods:A retrospective analysis was conducted on the data of 168 patients with hip PJI who underwent one-stage revision surgery combined with intra-articular antibiotics infusion in the Department of Joint Surgery, the First Affiliated Hospital of Xinjiang Medical University, from May 1, 2010 to April 30, 2024. There were 87 males and 81 females with an average age of 60.1±14.6 years (range: 21-89 years). The body mass index (BMI) was 24.9±4.6 kg/m 2 (range: 17-41 kg/m 2). PJI was diagnosed according to the criteria of Musculoskeletal Infection Society (MSIS) in 2011. AKI was diagnosed and classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. For AKI group and non-AKI group, risk factors were screened by univariate analysis on their age, gender, BMI, BMI≥30 kg/m 2 (yes/no), American Society of Anesthesiologists (ASA) score (II/III), hypertension, diabetes, chronic kidney disease (CKD), surgical side (left/right), duration of intravenous antibiotic use, duration of intra-articular antibiotic use, preoperative blood transfusion, postoperative blood transfusion, baseline hemoglobin value, anemia grade (none/mild/moderate), baseline serum creatinine value, baseline serum creatinine grade (normal/below normal range/above normal range). Variables with P<0.10 were included in the multivariate logistic regression model to identify independent risk factors. Results:The overall incidence of AKI was 9.52%(16/168), among which 50%(8 cases) were stage I AKI, transient and requiring no special treatment. 12.5% (2 cases) were stage II AKI and did not undergo dialysis. 37.5%(6 cases) were stage III AKI. One case needed temporary hemodialysis, and there was no patient requiring long-term dialysis. There were significant differences in age, diabetes, chronic kidney disease and ASA score between AKI group and non-AKI group ( P<0.05). The univariate logistic regression analysis revealed that there were significant differences in age ( P=0.005), BMI ( P=0.078), ASA score level Ⅲ ( P=0.037), diabetes ( P=0.025), CKD ( P=0.003), and low baseline serum creatinine level ( P=0.056). Multivariate logistic regression analysis showed that age, CKD and low baseline serum creatinine level were independent risk factors for AKI ( P<0.05). Conclusions:The incidence of AKI after one-stage revision surgery combined with local antibiotic use in the joint cavity was relatively low in the treatment of PJI after total hip arthroplasty. Hower elderly patients with a history of CKD, or a low baseline serum creatinine level before surgery were at higher risk of developing AKI.

The construction of the National Medical Center and the National Regional Medical Center in the Chengdu-Chongqing Economic Circle (referred to as the dual medical center construction) faces the challenges of insufficient integration of industry, academia, research, and medicine, as well as limited joint development and sharing of high-quality resources. It is urgent to promote the integration and coordinated development of regional education and technology talent resources through the integration of higher medical education, and to enhance the "four chains" synergy with the integration of industry and education as the core, thereby promoting the dual medical center construction. This study investigated and summarized the key issues in the dual medical center construction and the integration of higher medical education in the Chengdu-Chongqing Economic Circle. Based on the theoretical framework of four chain coordination (industry chain-talent chain-education chain-city chain), this study clarified the mechanisms by which integrated higher medical education can promote dual medical center construction. The study found that the integration of higher medical education can effectively promote the optimization of resources for dual medical center construction by constructing a collaborative mechanism of "industry education integration-joint talent cultivation-coordinated discipline construction-intercity cooperation". Based on the strengths in higher education resources in Chengdu and Chongqing, a five-dimension collaborative path was proposed: integrated development; technological leadership; talent oriented; government guidance; and market assistance. The research conclusion not only enhances the understanding of the integration of higher medical education, but also provides theoretical basis and practical reference for the dual medical center construction in the Chengdu-Chongqing Economic Circle. The proposed coordinated development also has reference value for the construction of medical centers in urban agglomerations such as the Beijing-Tianjin-Hebei Urban Agglomeration and the Yangtze River Delta.

Objective:To investigate the safety and effectiveness of the clinical application of minimally invasive transcatheter patent foramen ovale occlusion.Methods:A total of 123 patients who underwent transcatheter patent foramen ovale (PFO) occlusion at the Department of Cardiac Surgery of Beijing Anzhen Hospital from January 1, 2023, to December 31, 2023, were retrospectively analyzed. According to the surgical protocol, this study divided the patients into the conventional occlusion group (Group A, 53 cases) and the minimal invasive occlusion group (Group B, 70 cases). The patients were followed up for at least six months after surgery to evaluate the safety and effectiveness of the new method.Results:The surgical success rate was 100% in both groups. Intraoperative fluoroscopy time decreased by over 50% (7 min in group A and 3 min in group B, P<0.001). At the six-month postoperative follow-up, contrast-enhanced transcranial Doppler ultrasound sonography revealed seven positive results, two of which indicated large shunts. It was further reviewed for combined pulmonary arteriovenous fistula. One patient experienced a recurrence of stroke after the surgery. The patients' overall migraine and transient ischemia attack (TIA) were significantly relieved, and their overall VAS scores decreased significantly compared to the previous ones. Conclusion:The minimally invasive transcatheter PFO occlusion procedure is safe, reliable, and cost-effective. It warrants further follow-up and promotion. Meanwhile, transcatheter PFO occlusion is an effective treatment for preventing recurrent stroke and relieving symptoms like migraine and TIA in patients.