OBJECTIVE To provide valuable insights for the adjustment of anti-infectious regimens， identification of adverse reactions， and individualized pharmaceutical care in patients with critically severe scrub typhus. METHODS Clinical pharmacists actively participated in the pharmaceutical care process for a patient with severe scrub typhus leading to mixed shock undergoing continuous renal replacement therapy and extracorporeal membrane oxygenation. Initially， the patient received meropenem （1 g， q12 h， ivdrip）， in combination with doxycycline （0.1 g， q12 h， po）， which was later switched to meropenem （1 g， q8 h， ivdrip） along with omacycline （100 mg， qd， ivdrip） due to impaired gastrointestinal function. However， as the patient’s condition progressively deteriorated and the infection became uncontrolled， the clinical pharmacists recommended that the clinicians adjust the anti-infective regimen to meropenem （2 g， q8 h， ivdrip） combined with tigecycline （100 mg for first dose； 50 mg， q12 h for maintenance； ivdrip）. The clinicians followed the advice of the clinical pharmacists. After treatment， the patient’s symptoms exhibited significant improvement， accompanied by a notable decrease in inflammatory markers， indicating that the infection had been successfully controlled. However， due to continuously increasing bilirubin levels， in order to reduce the risk of drug-induced liver injury， the clinicians changed tigecycline to azithromycin （0.5 g， qd， ivdrip） following the recommendation of the clinical pharmacists. RESULTS Ultimately， metagenomic next-generation sequencing of the bronchoalveolar lavage fluid and blood specimens indicated that Orientia tsutsugamushi had been completely eradicated in the patient. CONCLUSIONS Tigecycline may be a viable therapeutic choice for patients with severe scrub typhus. In the context of critically ill patients with scrub typhus， combining tigecycline with azithromycin might potentially enhance the efficacy in eliminating Orientia tsutsugamushi.

ObjectiveTo evaluate the application of prostate-specific membrane antigen （PSMA）PET/CT in prostate biopsy screening， and propose effective strategies for prostate biopsy decision making based on PSMA PET/CT detection. MethodsA retrospective analysis was conducted on PSMA PET/CT imaging and clinical pathological data from 155 patients with suspected prostate cancer between January 2020 and December 2023. PRIMARY score was used as the standardized evaluation method for PSMA PET/CT in the diagnosis of prostate cancer. And compared the positive prostate biopsy rates， missed diagnosis rates and biopsy reduction rates were compared regarding different PRIMARY scores. Receiver operating characteristic （ROC） curves were used to analyze prostate-specific antigen （PSA） and its derived parameters and identify the most suitable supplementary screening indicators for combined use with the PRIMARY score. ResultsAmong patients with PRIMARY scores of 1 to 5， the proportions of patients diagnosed with prostate cancer were 15.8% （3/19）， 17.1% （7/41）， 50% （12/24）， 95.2% （20/21） and 98% （49/50）， respectively. Using PRIMARY score of 3-5 as the biopsy screening strategy resulted in a positive prostate biopsy rate of 85.3% and biopsy reduction rate of 38.7%， but a missed diagnosis rate of 11%. PSA density > 0.15 ng/（mL·cm³） was selected as a supplementary screening criterion to detect prostate cancer from patients with PRIMARY scores of 1-2. The combined application of the above two screening criteria reduced the missed diagnosis rate to 2.2%. ConclusionThis study proposes a novel biopsy screening strategy for suspected prostate cancer patients using PSMA PET/CT， that is， a PRIMARY score of 3-5 or a PRIMARY score of 1-2 but PSA density>0.15 ng/（mL·cm³）， which can effectively avoid unnecessary biopsies and significantly reduce the missed diagnosis rate.

Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.

Objective: To explore the application and clinical efficacy of red blood cell therapeutic apheresis in erythropoietic protoporphyria (EPP) and hereditary hemochromatosis (HH). Methods: 1) The EPP patient was hospitalized twice for "abdominal pain, nausea, vomiting, and brown urine". One and two sessions of red blood cell exchange/therapeutic plasma exchange (RCE/TPE) were respectively performed during the two hospitalizations. During each session, one RCE with 6-8 units of leukoreduced RBCs and 3-4 TPE procedures with 1 800-2 000 mL of frozen plasma was conducted. Biochemical parameters were monitored before and after treatment. 2) The HH patient was hospitalized for “repeatedly elevated aminotransferases”. Erythrocytapheresis was performed once, removing 550 mL of red blood cells, and venous phlebotomy was conducted once every 2 months subsequently. Blood routine and ferritin levels were assessed before and after treatment. Results: 1) During the first hospitalization, the EPP patient was relieved of the abdominal pain and brown urine after therapeutic apheresis. The total bilirubin level decreased from 141.8 μmol/L on admission to 68.6 μmol/L at discharge, with a symptom remission duration of 10 months. During the second hospitalization, the EPP patient still had recurrent abdominal pain after therapeutic apheresis. He developed psychiatric symptoms and gastrointestinal bleeding subsequently, accompanied by elevated bilirubin levels. Liver function deteriorated and the patient went into the state of the end-stage liver disease (ESLD). 2) For the HH patient, the hemoglobin level prior to erythrocytapheresis and vein phlebotomy was 150-160 g/L, with the lowest value occurring two days after erythrocytapheresis, decreasing to 107 g/L. The ferritin level before erythrocytapheresis was 2 428.08 ng/mL and it declined gradually after theraphy, with the lowest value occurring two months after erythrocytapheresis, decreasing to 1 094 ng/mL. The ferritin level was 1 114 ng/mL two months following the first vein phlebotomy, however it increased to 1 472 ng/mL two months after the second vein phlebotomy. Conclusion: RCE/TPE may alleviate protoporphyrin liver disease and help patients with bridging liver transplantation before EPP developments to ESLD. For HH patients with significantly elevated ferritin levels, erythrocytapheresis reduces serum ferritin more quickly and maintains its level longer relative to phlebotomy.

During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Objective: The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB). Materials and Methods: This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB. Results: In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%). Conclusion The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.