Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To analyze the clinical efficacy of arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip.Methods:A total of 30 patients (12 males and 18 females) with bilateral external snapping hip underwent arthroscopic transverse release of the iliotibial band through peritrochanteric space in Department of Sports Medicine, Senior Department of Orthopaedics, the Fourth Medical Center, Chinese PLA General Hospital were retrospectively analyzed from May 2021 and June 2022. The average age was 32.5±8.2 years (range, 17-51 years). At the same time, 30 patients who underwent arthroscopic external release of the iliotibial band through the external surface of the iliotibial band (external iliotibial band group) were selected as control group, including 13 males and 17 females, aged 29.5±6.8 years (range, 11-45 years). The visual analogue scale (VAS), modified Harris hip score (mHHS), and gluteal muscle contracture disability scale (GDS) were compared between the two groups at preoperative, 6 months postoperative, and final follow-up.Results:All patients successfully completed the operation and were followed up for 17.5±3.3 months (range, 12-25 months). The VAS scores of the two groups at the last follow-up were lower than those before operation ( P<0.05). The mHHS scores before operation, 6 months after operation and at the last follow-up in the peritrochanteric space group were 76.5 (67.0, 85.5), 98.5 (94.8, 100.0) and 100.0 (97.0, 100.0), respectively, and those in the external iliotibial band group were 80.5 (70.0, 86.0), 100.0 (96.0, 100.0) and 100.0 (99.5, 100.0). The differences in mHHS scores between the two groups were statistically significant for intragroup comparisons ( P<0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in mHHS scores between groups at different time points ( P>0.05). The GDS before operation, at 6 months after operation and at the last follow-up were 47.0 (35.8, 64.5), 90.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the peritrochanteric space group, and 51.0 (38.0, 64.5), 50.0 (81.0, 94.0) and 93.5 (89.8, 98.0) in the external iliotibial band group, respectively. The differences in GDS between the two groups were statistically significant for intragroup comparisons ( P< 0.05); of these, 6 months postoperatively and at the last follow-up were greater than preoperatively, with statistically significant differences ( P<0.05); the differences at 6 months postoperatively and at the last follow-up were not statistically significant ( P>0.05). There was no significant difference in GDS between groups at different time points ( P>0.05). Conclusion:Arthroscopic transverse release of the iliotibial band through peritrochanteric space for the treatment of external snapping hip can effectively reduce hip pain and improve hip function, with satisfactory clinical results, and can be used as an alternative treatment to transverse release through the external surface of the iliotibial band.

Percutaneous nephrolithotomy(PCNL)is the first-line treatment for complex kidney stones and can be performed in a variety of positions.Semi-supine combined lithotomy position,as a flexible,convenient,safe and effective position for PCNL,can be conducted in a retrograde approach under a single position,so it is suitable for the treatment of complex kidney stones.We will review the development characteristics and advantages of PCNL in semi-supine combined lithotomy position,and its application in the treatment of complex kidney stones.Based on this,we will further propose a minimally invasive treatment strategy for upper urinary tract calculi.

Objective:To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods:This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ 2 test or Fisher′s exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results:According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant( χ 2=4.459, P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant( χ 2=4.410, P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95% CI: 5.8 to 13.2 months) and 7.3 months (95% CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95% CI: 12.5 to 33.9 months) and 15.9 months (95% CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion:Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

Objective:To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods:This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ 2 test or Fisher′s exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results:According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant( χ 2=4.459, P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant( χ 2=4.410, P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95% CI: 5.8 to 13.2 months) and 7.3 months (95% CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95% CI: 12.5 to 33.9 months) and 15.9 months (95% CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion:Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

Objective:To evaluate the feasibility and safety of PT Scope (short for intelligent pressure and temperature controlled flexible ureteroscopy)combined with Thulium laser in the intracavitary treatment of upper urinary tract stones.Methods:A retrospective analysis was conducted on the clinical data of 13 patients with upper urinary tract stones who were treated with PT Scope combined with Thulium laser lithotripsy in Sun Yat-Sen Memorial Hospital from February to April 2024. There were 7 males and 6 females. The patients had a mean age of (46±10) years old, with an accumulated stone diameter of (25.8±13.3) mm. There were 7 cases of lower calyx stones (53.8%), and 3 cases of concomitant ureteral stones (23.1%).Four patients (30.8%) had positive preoperative urine cultures, and six patients (46.2%) had leukocyte counts greater than 100 cells/μl in their urine tests. The Thulium laser power was set at 45 W (1.5 J at 30 Hz, 0.3 J at 150 Hz). The renal pelvic pressure threshold was set at 30 mmHg (1 mmHg=0.133 kPa), and the temperature threshold at 43 ℃. Postoperatively, double J stents were placed for 2 to 4 weeks.Results:All 13 patients successfully completed the surgery. The median operative time was 30 (25, 90) minutes. The intraoperative average renal pelvic pressure in these 13 patients ranged from 8 mmHg to 24 mmHg, and the average renal pelvic temperature ranged from 25 ℃ to 34 ℃. Postoperatively, 1 patient experienced a fever (38.0 ℃) and 2 patients required analgesic treatment due to postoperative pain. There were no other intraoperative or postoperative complications. The median postoperative hospital stay was (1.5±0.8) days. The stone-free rate of 1 month was 84.6%(11/13).Conclusions:PT Scope combined with Thulium laser could effectively control renal pelvic pressure and temperature, achieve a high stone-free rate, and have a low complication rate. It is a safe and effective treatment for upper urinary tract stones.

Objective To investigate the differential diagnostic value of CT scan minimum attenuation values (minAVsCT) in adrenal adenomas and non-adenomas.Methods CT scan data of 89 cases of clinical and pathologically confirmed adrenal adenomas were subjected to retrospective analysis and compared with data of 46 cases involving 50 non-adenomas (25 metastases,20 pheochromocytomas,3 lymphomas,and 2 cortical carcinomas).The distributions of mean attenuation values (meanAVs) ￥ 10 Hu and minAVs ￥0 Hu and CT histogram analysis with ≥ 10％ negative pixels were observed in adrenal adenomas and non-adenomas,and the diagnostic sensitivity and specificity of these 3 methods for adenomas were calculated.Results The distributions of unenhanced meanAVs ￥ 10 Hu,minAVs ￥0 Hu,and CT histogram analysis with ≥ 10％ negative pixels among cases of adenoma and non-adenoma were 62.9％ (56/89) and 0％ (0/50) (x2=52.687,P=0.000),84.3％ (75/89) and 2％ (1/50) （x2=83.917,P=0.000),and 77.5％ (69/89) and 0％ (0/50) (x2=83.917,P=0.000),respectively.The respective diagnostic sensitivities,specificities,false negative rate (FNR),false positive rate (FPR),positive pre dictive value (PPV),negative predictive value (NPV) and accuracy of these 3 methods for adenomas were 62.9％vs 84.3％ vs 77.5％,100％ vs 98.0％ vs 100％,37.1％ vs 15.7％ vs 22.5％,0 vs 2％ vs 0,100％ vs 98.7％ vs 100％,60.2％ vs 77.8％ vs 71.4％,and 76.3％ vs 89.2％ vs 85.6％.Conclusion Although the specificity and PPV of minAVs≤0Hu is slightly less than meanAVs≤10Hu and CT histogram analysis with ≥ 10％ negative pixels,it exhibits the best sensitivity and accuracy with a simple operation,and is thus suitable for clinical application.

Objective To discuss the predictive value of multiple ultrasonic features combination in diagnosis of thyroid papillary carcinoma (PTC) more than 1.0 cm in diameter. Methods The ultrasonic features of 258 PTC nodules from 251 patients and 207 nodular goiter (NG) nodules from 190 patients in the First People′s Hospital of Hangzhou were retrospectively analyzed. All the nodules were confirmed by pathological examination after surgery. The ultrasonic features included the shape of nodules, internal echo,anteroposterior/transverse diameter ratio (A/T), and microcalcification. The χ2 test was used to analyze the differences of ultrasonic features between PTC and NG. Multi-variate analyses (Logistic regression) was used to analyze the predictive risk ultrasonic features of PTC. The sensitivity and specificity of ultrasonic features were analyzed based on the gold standard of pathological results. Results There were significantly differences between 258 PTC nodules and 207 NG nodules in irregular shape, hypoechogenicity,A/T > 1 and microcalcification (χ2 values were 121.511, 105.411, 41.483, 121.072, all P < 0.01). The results of Logistic regression showed that irregular shape, hypoechogenicity, A/T>1 and microcalcification were risk ultrasonic features of PTC. And their OR values were 5.013 (95%CI 2.919-8.610), 5.811 (95%CI 3.411-9.901), 15.399 (95%CI 7.576-31.301), 4.141 (95%CI 1.687-10.164) respectively. The sensitivity and specificity of single ultrasonic feature were 26.0%-79.5% and 71.5%-96.1%; the sensitivity and specificity of two ultrasonographic features combination were 11.2%-57.0% and 92.3%-99.0%; and the sensitivity and specificity of three or four ultrasonographic features combination were 8.1%-31.8% and 99.0%-99.5%.Conclusions Irregular shape, hypoechogenicity, A/T> 1 and microcalcification of thyroid neoplasm are important ultrasonic features of PTC. Although the sensitivity of single ultrasonic feature in diagnosing PTC is higher than that of multiple features combination, it has a lower specificity. Therefore, combination of multiple ultrasonographic features can improve the specificity in diagnosing PTC and reduce the misdiagnosis of PTC.

OBJECTIVETo investigate the microstructure of dental zirconia ceramics prepared by two-step sintering.

METHODSNanostructured zirconia powder was dry compacted, cold isostatic pressed, and pre-sintered. The pre-sintered discs were cut processed into samples. Conventional sintering, single-step sintering, and two-step sintering were carried out, and density and grain size of the samples were measured. Afterward, T1 and/or T2 of two-step sintering ranges were measured. Effects on microstructure of different routes, which consisted of two-step sintering and conventional sintering were discussed. The influence of T1 and/or T2 on density and grain size were analyzed as well.

RESULTSThe range of T1 was between 1450 degrees C and 1550 degrees C, and the range of T2 was between 1250 degrees C and 1350 degrees C. Compared with conventional sintering, finer microstructure of higher density and smaller grain could be obtained by two-step sintering. Grain growth was dependent on T1, whereas density was not much related with T1. However, density was dependent on T2, and grain size was minimally influenced.

CONCLUSIONTwo-step sintering could ensure a sintering body with high density and small grain, which is good for optimizing the microstructure of dental zirconia ceramics.