OBJECTIVE To establish a method for simultaneous determination of venetoclax， busulfan and voriconazole in plasma of patients with acute myeloid leukemia （AML）， and apply it clinically. METHODS Plasma samples were subjected to protein precipitation using acetonitrile and subsequently analyzed by liquid chromatography-tandem mass spectrometry （LC-MS/MS） using venetoclax-D 8 ， busulfan-D 8 and posaconazole as internal standards. The separation was performed on a Phenomenex Kinetex ® C 18 column with a mobile phase composed of 0.1% formic acid solution （2 mmol/L ammonium acetate）-0.1% formic acid in acetonitrile （gradient elution） at a flow rate of 0.8 mL/min. The column temperature was set at 40 ℃， the sample size was 5 μL， and the total run time was 3.10 min. An electrospray ionization source was employed， and positive ion scanning was conducted using multiple reaction monitoring mode. The ion pairs used for quantitative analysis included m/z 868.4→636.3 （venetoclax）， m/z 264.1→151.1 （busulfan）， and m/z 350.1→224.0 （voriconazole）. The above LC-MS/MS method was adopted to determine plasma concentrations of venetoclax and voriconazole in 10 AML patients， as well as plasma concentration of busulfan in 5 patients undergoing conditioning treatment for allogeneic hematopoietic stem cell transplantation. RESULTS The linear ranges of venetoclax， busulfan and voriconazole were 50-10 000， 15-3 000 and 50-10 000 ng/mL， respectively （ R 2 ≥0.999 0）， with lower limits of quantification of 50， 15 and 50 ng/mL， respectively. The RSDs of intra-day and inter-day precision tests for all three analytes were all less than 10%， with accuracy （relative errors） ranging from －10.00% to 12.96%. The average extraction recovery ranged from 92.54% to 100.95%， and the average matrix effect was 89.98%-101.49%. Dilution reliability covered all dilution factors used in the test samples， and the absolute values of relative errors in stability tests were all≤16.25%. The plasma concentrations of venetoclax， busulfan and voriconazole in enrolled patients were 496.20-4 250.45， 233.48-2 002.28 and 475.51-5 710.18 ng/mL， respectively. CONCLUSIONS The LC-MS/MS method established in this study is rapid， sensitive and easy to operate， and can be used for the therapeutic drug monitoring of venetoclax， busulfan and voriconazole.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a significant threat to public health. Advances in medical science and increased screening awareness have improved early-stage diagnosis rates, allowing more patients to undergo radical treatment at initial diagnosis. Concurrently, ongoing developments in treatment modalities have expanded the options available for both patients and clinicians. The challenge now lies in making informed decisions to achieve individualized precision medicine, which merits thorough exploration. This article aims to review the latest research on personalized treatment strategies for early-stage HCC, providing a reasonable reference and valuable insights for clinicians.

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer. Hepatic resection is the preferred treatment for colorectal cancer liver metastasis (CRLM). However, a disappointingly small proportion of patients are deemed suitable for surgical resection upon initial consultation. Failure to adequately address these metastatic tumors results in a dire 5-year survival rate of less than 5%. In recent times, thermal ablation, a minimally invasive procedure aimed at controlling local tumor progression, has undergone rigorous validation and garnered recognition for its effectiveness and safety in managing CRLM. This article endeavors to review the advancements in research concerning thermal ablation in the treatment of CRLM, exploring its efficacy, safety profile, and the promising avenues for its clinical application.

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a significant threat to public health. Advances in medical science and increased screening awareness have improved early-stage diagnosis rates, allowing more patients to undergo radical treatment at initial diagnosis. Concurrently, ongoing developments in treatment modalities have expanded the options available for both patients and clinicians. The challenge now lies in making informed decisions to achieve individualized precision medicine, which merits thorough exploration. This article aims to review the latest research on personalized treatment strategies for early-stage HCC, providing a reasonable reference and valuable insights for clinicians.

The liver is the most common anatomical site for hematogenous metastases of colorectal cancer. Hepatic resection is the preferred treatment for colorectal cancer liver metastasis (CRLM). However, a disappointingly small proportion of patients are deemed suitable for surgical resection upon initial consultation. Failure to adequately address these metastatic tumors results in a dire 5-year survival rate of less than 5%. In recent times, thermal ablation, a minimally invasive procedure aimed at controlling local tumor progression, has undergone rigorous validation and garnered recognition for its effectiveness and safety in managing CRLM. This article endeavors to review the advancements in research concerning thermal ablation in the treatment of CRLM, exploring its efficacy, safety profile, and the promising avenues for its clinical application.

Objective:To explore the effect of preoperative intensive functional training on the balance and functional recovery of patients with knee osteoarthritis (KOA) receiving total knee arthroplasty (TKA).Methods:Sixty KOA patients were randomly divided into an outpatient group, a home-based group and a control group, each of 20. Before their TKAs, both the outpatient and home-based groups underwent intensive functional training for 4 weeks, while the control group did nothing special. After the TKA, all received 4 weeks of standardized postoperative rehabilitation training. Before any training, after the 4 weeks of preoperative training and 4 weeks after the TKAs, all of the subjects performed the timed up and go test (TUGT), and their joint range of motion (ROM) was recorded. They also completed the 30-second chair stand strength test (30sCST), and the 6-minute walk exercise endurance test (6MWT). KOA osteoarthritis indices (WOMACs) were also recorded.Results:After the 4 weeks of preoperative training, significant differences were observed in the trajectory length, elliptical area and TUGT times of both the outpatient and home-based groups. Four weeks after the TKAs, significant differences were observed in all of the measurements in all three groups, but the results of the outpatient and home-based groups were significantly better than those of the control group, on average. After the 4 weeks of postoperative training, there were significant differences between the outpatient and home-based groups in terms of the average knee flexion angle, knee extension angle, 30sCST and 6MWT results. There were significant differences among the 3 groups in all of the measurements 4 weeks after the TKAs, with those of the two training groups showing significantly better results than the control group. The pain scores, stiffness scores, function scores and total WOMAC scores had improved significantly compared with the control group, but the average function and total WOMAC scores of the outpatient group (24.25±2.38) and (35.41±3.02) were then significantly superior to the home-based group′s averages.Conclusions:Intensive preoperative functional training conducted in an outpatient clinic or at home can significantly improve the balance, lower limb strength, exercise endurance and symptoms of KOA patients after TKA.

Objective:To investigate the therapeutic efficacy of programmed death-1(PD-1)inhibitors in combination with drug-eluting beads transcatheter arterial chemoembolization(DEB-TACE)and radiofrequency ablation(RFA), as well as their impact on the prognosis of older patients with primary hepatocellular carcinoma(HCC).Methods:In this prospective cohort study, 120 patients aged 65 years and older with HCC at stage Ⅱb-Ⅲb were randomly assigned to an observation group (n=60)and a control group (n=60)between January 2021 and January 2024.The control group received DEB-TACE followed by RFA, while the observation group received a PD-1 inhibitor in combination with DEB-TACE followed by RFA, with both interventions lasting for 12 weeks.The clinical efficacy of the treatments in both groups was assessed, and changes in serum tumor markers before and after treatment were compared between the two groups.Safety was evaluated, survival data were recorded during follow-up, and the effects of different therapeutic regimens on patient prognosis were analyzed.Results:The disease control rate(DCR)and objective response rate(ORR)in the observation group were 88.33% and 78.33%, respectively, which were higher than those in the control group (71.67% and 28.33%, χ2=5.208, 30.134, P=0.022, <0.001). After treatment, levels of serum tumor markers (alpha fetoprotein, carbohydrate antigen 125, vascular endothelial growth factor)decreased in both groups (all P<0.05), with levels in the observation group being lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (all P>0.05). By the end of follow-up, which ranged from 2 to 33 months, there were 15 death cases in the observation group, resulting in a cumulative survival rate of 75.00%(45/60) and a mean survival of 25.95 months.In the control group, there were 25 death cases, with a cumulative survival rate of 58.33%(35/60)and a mean survival of 20.33 months.The results of the Kaplan-Meier function analysis were as follows: Log-rank χ2=5.747, P=0.017; Breslow χ2=3.124, P=0.077.The results of the multivariate Cox regression analysis indicated that PD-1 inhibitor combined with DEB-TACE sequential RFA was a protective factor against death in older patients with primary HCC( HR=0.680, 95% CI: 0.463-0.998, P=0.014). Conclusions:The curative effect and safety of PD-1 inhibitor combined with DEB-TACE and RFA are favorable in older patients with advanced HCC.

Objective:To investigate the effect of progressive resistance training on inflammatory markers, motor function and quality of life in the elderly after total knee arthroplasty (TKA).Methods:This study was a randomized controlled trial. A total of 46 elderly patients aged≥60 years who underwent total knee arthroplasty in the Affiliated Hospital 6 of Nantong University from January 2023 to June 2024 were selected and divided into experimental group and control group by computer random number method (23 cases in each group). The control group received routine rehabilitation management intervention, progressive resistance training was added to the experimental group on the basis of the control group, and all patients were intervened for 4 weeks. Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), 30-Second Chair Stand Test (30sCST), Knee Society Score (KSS), and World Health Organization Quality of Life Scale-Brief Form Questionnaire (WHOQOL-BREF) scores were measured at 1 day before operation, 2 weeks and 4 weeks after operation, and were compared respectively.Results:At 2 and 4 weeks after operation, the levels of IL-6 [(22.44±2.17) and (9.91±1.41) pg/ml], CRP[(19.61±2.20) and (3.17±0.40) mg/L] and ESR[(44.85±3.78) and (28.28±3.31) mm/1 h] in the experimental group were significantly lower than those in control group [IL-6: (24.65±1.77) and (11.35±1.67) pg/ml, CRP: (23.24±2.69) and (4.15±0.45) mg/L and ESR: (48.54±3.66) and (34.60±2.98) mm/1 h](all P<0.05). At 2 and 4 weeks after operation, the 30sCST[(9.87±0.92) and (11.83±1.03) times], clinical scores of KSS[(48.44±3.13) and (71.09±3.30) points], functional scores of KSS[(40.44±3.96) and (69.35±4.07) points] in the experimental group were significantly higher than those in control group [30sCST: (9.30±0.70) and (10.52±0.79) times, clinical scores of KSS: (46.17±2.86) and (67.00±2.89) points, functional scores of KSS: (38.91±3.68) and (66.30±5.05) points](all P<0.05). At 2 weeks after operation, the scores of physical health, mental health and social relations in the WHOQOL-BREF of the experimental group [(16.96±1.02), (17.96±1.46) and (6.74±0.62) points], which were significantly higher than those in the control group [(16.09±1.08), (17.14±1.12), (6.44±0.51) points](all P<0.05). There was no significant difference in the environmental condition score between the two groups. At 4 weeks after operation, the scores of physical health, mental health, social relations and environmental conditions in WHOQOL-BREF of the experimental group [(22.09±1.81), (22.17±2.19), (12.09±1.28) and (33.91±2.26) points] were significantly higher than those in the control group [(19.65±1.80), (20.39±1.95), (10.17±1.30), (31.96±2.51) points] (all P<0.05). Conclusion:Progressive resistance training can effectively reduce the inflammatory response in the elderly after total knee arthroplasty, enhance lower limb muscle strength and knee joint function, and improve the quality of life.

Objective:To analyze the short-term efficacy and safety of robot-assisted laparoscopic partial nephrectomy（RAPN）for non-metastatic pathological stage T 3a renal cell carcinoma. Methods:The clinical and pathological data of 45 patients with pathologically confirmed non-metastatic T 3a renal cell carcinoma who underwent RAPN at Sun Yat-sen University Cancer Center between January 2016 and December 2023 were retrospectively reviewed. There were 30 males and 15 females. The average age of the cohort was（54.3±10.7）years，and the average clinical tumor diameter was（4.9±1.8）cm. Of all the patients，35（77.8%）were asymptomatic，7（15.6%）presented with hematuria，and 3（6.7%）presented with lumbar pain. Preoperative imaging assessed 34 patients（75.6%）as having clinical stage T 3a，all suspected of involving the collecting system or perirenal fat invasion；the remaining 11 patients（24.4%）were assessed as having stage T 1-2 disease. The median R.E.N.A.L. nephrectomy score was 8.0（7.0，10.0）. A history of hypertension，diabetes，or chronic kidney disease was present in 18 patients（40.0%）. The primary endpoint was progression-free survival，and the secondary endpoints included postoperative complications and short-term renal function outcomes. Survival curve was estimated using the Kaplan-Meier method，and renal function comparisons were made using the paired t-test. Results:The RAPN was performed through a transabdominal approach in 32 patients（71.1%），with a median estimated blood loss of 150.0（50.0，300.0）ml. Seven（15.6%）patients required intraoperative blood transfusion. The median length of postoperative hospital stay was 4.0（4.0，6.0）days. Postoperative complications occurred in 6 patients（13.3%），including 5（11.1%）with mild complications and 1（2.2%）with a severe complication. Renal function returned to baseline in 24 of 39 evaluable patients（61.5%），while 3 patients（7.7%）developed surgery-related chronic kidney disease 3 to 12 months postoperatively，but none required dialysis. The median follow-up time was 31.8（22.7，50.9）months，12（26.7%）patients received programmed cell death protein 1 inhibitor adjuvant therapy postoperatively. During follow-up，3 patients experienced tumor recurrence，the 3-year progression-free survival rate of the entire cohort was 95.4%.Conclusions:For some carefully selected patients with T 3a renal cell carcinoma，RAPN performed by experienced surgeons is a feasible and safe option，providing excellent short-term oncological outcomes，complication control，and renal function recovery. The long-term efficacy remains to be seen.