OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

Objective:To analyze the effects of Mulligan technique combined with isokinetic exercise training (IET) on isokinetic muscle strength and neuromuscular control ability in patients with knee osteoarthritis (KOA).Methods:A retrospective case-control study was conducted. A total of 49 patients with KOA who underwent IET at Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to January 2022 were included in the control group. An additional 49 patients with KOA who received Mulligan technique and IET at the same hospital from June 2022 to June 2023 were included in the observation group. Both groups were treated for 8 successive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lysholm score, proprioception metrics [including average track error (ATE) and test time execution (TTE)], isokinetic muscle strength [peak torque (PT) and average power (AP) for flexors and extensors at 60°/s, 90°/s, and 120°/s)]were compared between the two groups before and after 4 and 8 weeks of intervention. Additionally, Visual Analog Scale score was compared between the two groups at baseline and after 8 weeks of intervention.Results:There was no statistically significant difference in WOMAC score, Lysholm score, or PT and AP levels for flexor and extensor muscles at 60°/s, 120°/s, and 180°/s between the two groups before intervention (all P > 0.05). After 4 and 8 weeks of intervention, the levels of PT and AP for both flexors and extensors at 60°/s, 120°/s, and 180°/s, as well as the Lysholm scores, were significantly higher in the observation group compared with the control group [PT level: t = -0.10, -3.03, -3.85, -0.35, -3.62, -3.95, -0.27, -5.51, -6.52, -1.13, -2.74, -3.68, -0.09, -2.91, -5.79, -0.13, -4.66, -6.05; AP level: t = -0.23, -4.77, -6.15, 0.01, -3.10, -3.75, -0.13, -3.73, -3.44, 0.16, -2.09, -4.05, -0.17, -3.71, -3.51, -0.27, -3.26, -3.69; Lysholm score: t = -7.17, -6.44; all P < 0.05]. After 4 and 8 weeks of intervention, the WOMAC score, ATE, and TTE in the observation group were significantly lower than those in the control group [WOMAC score: t = 3.68, 0.64; ATE level: t = 3.88, 4.13; TTE level: t = 4.86, 4.60; all P < 0.05]. After 8 weeks of intervention, both groups had lower Visual Analog Scale scores compared with their scores before the intervention (U control group = -8.75, U observation group = -8.63), with the observation group showing significantly lower scores than the control group ( U = -5.95, P < 0.001). Conclusions:The Mulligan technique combined with IET can effectively alleviate knee joint pain in patients with KOA, promote the recovery of knee joint function, enhance proprioceptive recovery, and improve neuromuscular control abilities.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,oxypaeoniflorin,catechin,epicatechin,albiflorin,paeoniflorin,rutin,calycosin-7-glucoside,syringaldehyde,ferulic acid,coumarin,ononin,calycosin,cinnamic alcohol,cinnamic acid,benzoylpaeoniflorin,cinnamaldehyde,astragaloside,astragaloside Ⅲ,6-gingerol in Huangqi Guizhi Wuwu Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Thermo Scientific Hypersil GOLD column(150 mmx4.6 mm,3 μm),with the mobile phase comprising of 0.015％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion modes with multiple reaction monitoring.RESULTS Twenty-one constituents showed good linear relationships within their own ranges(r＞0.990 5),whose average recoveries were 93.99％-108.52％with the RSDs of 1.04％-5.97％.CONCLUSION This simple,feasible,stable and reliable method can be used for the quality control of Huangqi Guizhi Wuwu Decoction.

Objective:To analyze the effects of Mulligan technique combined with isokinetic exercise training (IET) on isokinetic muscle strength and neuromuscular control ability in patients with knee osteoarthritis (KOA).Methods:A retrospective case-control study was conducted. A total of 49 patients with KOA who underwent IET at Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to January 2022 were included in the control group. An additional 49 patients with KOA who received Mulligan technique and IET at the same hospital from June 2022 to June 2023 were included in the observation group. Both groups were treated for 8 successive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lysholm score, proprioception metrics [including average track error (ATE) and test time execution (TTE)], isokinetic muscle strength [peak torque (PT) and average power (AP) for flexors and extensors at 60°/s, 90°/s, and 120°/s)]were compared between the two groups before and after 4 and 8 weeks of intervention. Additionally, Visual Analog Scale score was compared between the two groups at baseline and after 8 weeks of intervention.Results:There was no statistically significant difference in WOMAC score, Lysholm score, or PT and AP levels for flexor and extensor muscles at 60°/s, 120°/s, and 180°/s between the two groups before intervention (all P > 0.05). After 4 and 8 weeks of intervention, the levels of PT and AP for both flexors and extensors at 60°/s, 120°/s, and 180°/s, as well as the Lysholm scores, were significantly higher in the observation group compared with the control group [PT level: t = -0.10, -3.03, -3.85, -0.35, -3.62, -3.95, -0.27, -5.51, -6.52, -1.13, -2.74, -3.68, -0.09, -2.91, -5.79, -0.13, -4.66, -6.05; AP level: t = -0.23, -4.77, -6.15, 0.01, -3.10, -3.75, -0.13, -3.73, -3.44, 0.16, -2.09, -4.05, -0.17, -3.71, -3.51, -0.27, -3.26, -3.69; Lysholm score: t = -7.17, -6.44; all P < 0.05]. After 4 and 8 weeks of intervention, the WOMAC score, ATE, and TTE in the observation group were significantly lower than those in the control group [WOMAC score: t = 3.68, 0.64; ATE level: t = 3.88, 4.13; TTE level: t = 4.86, 4.60; all P < 0.05]. After 8 weeks of intervention, both groups had lower Visual Analog Scale scores compared with their scores before the intervention (U control group = -8.75, U observation group = -8.63), with the observation group showing significantly lower scores than the control group ( U = -5.95, P < 0.001). Conclusions:The Mulligan technique combined with IET can effectively alleviate knee joint pain in patients with KOA, promote the recovery of knee joint function, enhance proprioceptive recovery, and improve neuromuscular control abilities.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,oxypaeoniflorin,catechin,epicatechin,albiflorin,paeoniflorin,rutin,calycosin-7-glucoside,syringaldehyde,ferulic acid,coumarin,ononin,calycosin,cinnamic alcohol,cinnamic acid,benzoylpaeoniflorin,cinnamaldehyde,astragaloside,astragaloside Ⅲ,6-gingerol in Huangqi Guizhi Wuwu Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Thermo Scientific Hypersil GOLD column(150 mmx4.6 mm,3 μm),with the mobile phase comprising of 0.015％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion modes with multiple reaction monitoring.RESULTS Twenty-one constituents showed good linear relationships within their own ranges(r＞0.990 5),whose average recoveries were 93.99％-108.52％with the RSDs of 1.04％-5.97％.CONCLUSION This simple,feasible,stable and reliable method can be used for the quality control of Huangqi Guizhi Wuwu Decoction.

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular

Background: and Purpose This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). Methods: We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. Results: In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). Conclusion An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.