Introduction: Itch, an uncomfortable sensation leading to the urge to scratch, is often inadequately managed by conventional antihistamine drugs, which can be ineffective in certain pruritic conditions and cause undesirable side effects. Therefore, there is a need to identify new pharmacologically potent antipruritic compounds with fewer side effects. A synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)-cyclohexanone (BHMC), a derivative of curcumin - a bioactive compound found in turmeric - has demonstrated various pharmacological ac-tivities. Previous studies have shown that BHMC possesses antinociceptive and anti-inflammatory properties. This study aimed to investigate the antipruritic effects of BHMC in mice models of induced pruritus. Materials and Meth-ods: The pruritus in mice was induced using compound 48/80, substance P, histamine, and serotonin to establish an itch-induced mouse model. BHMC was administered intraperitoneally (i.p.) at doses of 0.1, 0.3, and 1.0 mg/kg. Results: BHMC significantly reduced pruriceptive responses in all models tested and notably inhibited compound 48/80 and substance P-induced mast cell degranulation in skin tissues. Conclusions: These findings suggest that BHMC inhibits pruriceptive responses in mice, likely through the inhibition of mast cell degranulation and/or direct antagonism of peripheral histamine and serotonin receptors. This may warrant further exploration of the antipruritic effect of BHMC in clinical trials for the betterment of animal and human health.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective·To investigate the clinicopathologic features,gene mutation profile,and real-world survival prognosis of diffuse large B-cell lymphoma(DLBCL)with pulmonary involvement.Methods·The clinical data of 110 patients with newly diagnosed,pathologically confirmed DLBCL and pulmonary involvement at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,between August 2003 and December 2022 were retrospectively collected and analyzed.Evaluation of the efficacy of treatment,survival analyses,and univariate and multivariate analyses were performed in 88 patients who received a first-line regimen based on rituximab in combination with cyclophosphamide,doxorubicin/epirubicine,vincristine,and prednisone(R-CHOP).A total of 74 patients underwent targeted DNA sequencing of 55 lymphoma-related genes and were evaluated for mutations.Results·Among the 110 patients,72(65.5%)were>60 years old,52(47.3%)were female,92(83.6%)presented with Ann Arbor stage Ⅲ?Ⅳ,20(18.2%)had ECOG scores≥2,75(68.2%)had elevated lactate dehydrogenase(LDH)levels,79(71.8%)had≥2 extranodal involvements,32(31.4%)were classified as germinal center B-cell subtype,22(26.8%)were diagnosed with double expressor lymphoma,and 4(4.6%)with double-hit lymphoma.Among the patients treated with R-CHOP-based first-line regimens,the objective response rate(ORR)was 68.2%,the 5-year progression-free survival(PFS)rate was 43.7%,and the 5-year overall survival(OS)rate was 65.4%.Univariate analysis showed that elevated LDH and ECOG score≥2 were poor prognostic factors for PFS and OS,and mutations in PIM1 and CD79B were poor prognostic factors for PFS among high-frequency mutations.Multivariate analysis showed that elevated LDH was an independent adverse prognostic factor for PFS(HR=2.47,95%CI 1.28?4.77)and OS(HR=2.71,95%CI 1.21 ? 6.07).Targeted sequencing results showed that PIM1(25.7%),MYD88(24.3%),TP53(18.9%),CD79B(17.6%),KMT2D(17.6%),and TNFAIP3(16.2%)were the high-frequency mutations with mutation rates over 15%.Conclusion·Elevated LDH is an independent adverse prognostic factor for PFS and OS in DLBCL with pulmonary involvement.Mutations in PIM1,MYD88,TP53,CD79B,KMT2D,and TNFAIP3 are frequently observed in this population.

Aim To construct and analyze the genotype of G protein-coupled receptor kinase 2(GRK2)conditional knockout mice in synoviocytes,and to provide an animal model for stud-ying the function of GRK2 in synoviocytes.Methods Grk2flox/+mice were bred to generate Grk2flox/flox mice,Grk2flox/flox mice were bred to Col1a1-iCre+mice,Grk2flox/+Col1a1-iCre+mice were bred to Grk2flox/flox mice.Grk2flox/flox Col1a1-iCre+mice were ob-tained as target mice.DNA was extracted and amplified by PCR to identify the genotype.Western blot was used to verify the effect of Grk2 knockout in synovium,liver and kidney tissues.HE staining was used to detect the effects of Grk2 conditional knockout in synovial cells on ankle synovium,liver and kidney tissues.Multiple immunofluorescence was used to detect GRK2 expression in synovial cells.Results The results of gene iden-tification showed that Grk2flox/flox Col1a1-iCre+mice had both Flox and Col1a1-iCre genotypes.Western blot results showed that GRK2 expression decreased in synovial tissues of Grk2flox/flox Col1a1-iCre+mice,but there was no significant change in the expression of GRK2 in liver and kidney tissues.HE staining showed that Grk2flox/flox Col1a1-iCre+mice had no significant pathological changes in the ankle synovium,liver and kidney.The results of multiple immunofluorescence showed that GRK2 expression in synovial cells of Grk2flox/flox Col1a1-iCre+mice de-creased.Conclusion Grk2 conditional knockout mice in syno-viocytes are successfully constructed and identified,which pro-vides an animal model for further study of the role of GRK2 in synovial-related diseases.

Aim To observe the mechanism of salvian-olic acid B(SalB)against oxygen glucose deprivation/re-oxygenation(OGD/R)injury in H9c2 cardiomyo-cytes.Methods The protective concentration of SalB against OGD/R-injured H9c2 cardiomyocytes was screened by CCK-8 assay.The levels of lactate dehy-drogenase(LDH),aspartate transaminase(AST)and creatine kinase(CK)were detected by ELISA kit.The mechanism of action of SalB on OGD/R-injured H9c2 cardiomyocytes was explored using high-through-put sequencing of the transcriptome.The binding of SalB to differential proteins was assessed using molecu-lar docking assays.Fatty acid content was determined using free fatty acid kits.The relative expressions of mRNA and protein of differential genes were verified by RT-qPCR and Western blot.The causal relationship between the target of action of SalB and heart failure was examined by Mendelian randomization experiment.Results SalB protected OGD/R-injured H9c2 cardio-myocytes and significantly reduced the levels of CK,LDH and AST compared with the blank control group.One hundred differential genes were screened by tran-scriptome sequencing,which were mainly involved in fatty acid elongation,central carbon metabolism of cancer,tryptophan metabolism pathways.Molecular docking showed that SalB had good binding energy to differential proteins.The mRNA and protein expression of core differential genes Elovl6,Echs1 and Acot1 were consistent with the transcriptome sequencing results.SalB reduced fatty acidsafter OGD/R injury.Mende-lian randomization experiments suggested that SalB might reduce the risk of heart failure through fatty acid metabolism,thereby reducing the risk of heart failure.Conclusion SalB can protect H9c2 cardiomyocytes after OGD/R injury by down-regulating Elovl6,Echs1 and Acot1 expression through the fatty acid metabolism pathway.

Objective To investigate the impact of different application methods of tissue compensators(bolus)on the skin dose delivered to the chest wall following radical mastectomy for breast cancer.Methods A retrospective analysis was conducted on 60 female patients who underwent radical mastectomy and required chest wall radiotherapy at the hospital between January 2023 and March 2025.The Pinnacle3 9.10 radiotherapy planning system(TPS)was utilized to design two VMAT dual semi-arc radiotherapy plans for each patient,with a prescribed target dose of 50 Gy delivered in 2 Gy fractions over 25 sessions.In Plan 1,a Bolus was applied and optimized during the first 15 fractions,and subsequently removed for the remaining 10 fractions without re-optimization.The sub-field configuration and dose weighting from the initial optimization were retained,and only dose recalculations were performed.The final treatment plan combined both the Bolus-included and Bolus-excluded phases.In contrast,Plan 2 involved the application and optimization of Bolus during the first 15 fractions,followed by its removal and re-optimization of the plan for the last 10 fractions.The two optimized plans were then combined for the overall treatment delivery.Data from the two plan groups were analyzed using a paired sample t-test with SPSS 29.0 software.Results There was a statistically significant difference(P＜0.05)in skin Dmean,V52.5,and V55;heart Dmean,V5,V30,and V40;affected lung Dmean,V5,and V20;PRVcord Dmean and Dmax;healthy breast Dmean,V5,and V10;affected humeral head Dmean and V30;as well as PTV Dmean,V50,V55,D2％,D98％,CI,and MU.Moreover,the dose distribution on the target layer and the DVH curves showed marked differences.However,no statistically significant difference was observed in PTV HI(P=0.125).Conclusion The combination of the two optimized plans,consisting of 15 fractions with bolus and 10 fractions without bolus,more accurately reflects the dose distri-bution within the planned target area and organs at risk,thereby providing enhanced protection for the patient's chest wall skin.

Aim To observe the mechanism of salvian-olic acid B(SalB)against oxygen glucose deprivation/re-oxygenation(OGD/R)injury in H9c2 cardiomyo-cytes.Methods The protective concentration of SalB against OGD/R-injured H9c2 cardiomyocytes was screened by CCK-8 assay.The levels of lactate dehy-drogenase(LDH),aspartate transaminase(AST)and creatine kinase(CK)were detected by ELISA kit.The mechanism of action of SalB on OGD/R-injured H9c2 cardiomyocytes was explored using high-through-put sequencing of the transcriptome.The binding of SalB to differential proteins was assessed using molecu-lar docking assays.Fatty acid content was determined using free fatty acid kits.The relative expressions of mRNA and protein of differential genes were verified by RT-qPCR and Western blot.The causal relationship between the target of action of SalB and heart failure was examined by Mendelian randomization experiment.Results SalB protected OGD/R-injured H9c2 cardio-myocytes and significantly reduced the levels of CK,LDH and AST compared with the blank control group.One hundred differential genes were screened by tran-scriptome sequencing,which were mainly involved in fatty acid elongation,central carbon metabolism of cancer,tryptophan metabolism pathways.Molecular docking showed that SalB had good binding energy to differential proteins.The mRNA and protein expression of core differential genes Elovl6,Echs1 and Acot1 were consistent with the transcriptome sequencing results.SalB reduced fatty acidsafter OGD/R injury.Mende-lian randomization experiments suggested that SalB might reduce the risk of heart failure through fatty acid metabolism,thereby reducing the risk of heart failure.Conclusion SalB can protect H9c2 cardiomyocytes after OGD/R injury by down-regulating Elovl6,Echs1 and Acot1 expression through the fatty acid metabolism pathway.

Objective:To compare the effect and complications of immediate and delayed restoration after immediate implantation in the anterior tooth region of elderly patients with periodontal disease.Methods:A total of 86 elderly patients with periodontal disease who underwent anterior dental restoration admitted to the Second People′s Hospital of Huai′an from February 2019 to August 2021 were prospectively selected and divided into observation group ( n=43) and control group ( n=43) according to the order of admission. Both groups received immediate implantation, the observation group received immediate repair after surgery, the control group received delayed repair after surgery. Both groups were followed up for 12 months after implantation. The soft tissue around the implant, White Aesthetic Score (WES), Pink Esthetic Score (PES), bone resorption value, implant success rate and complications were compared between the two groups. Results:One month after repair, periodontal probing depth (PD) in observation group was lower than that in the control group ( P<0.05), and modified sulcus bleeding index (mSBI) was higher than that in the control group ( P<0.05). At 3 months after repair, PD in both groups was lower than that at 1 month after repair (all P<0.05), and PD in the observation group was lower than that in the control group ( P<0.05), while mSBI in the observation group was lower than that at 1 month after repair ( P<0.05), and there was no statistical significance between the two groups ( P>0.05). Six months after repair, WES scores and PES scores in the observation group were higher than those in the control group ( P<0.05). At 6 months after repair, the bone resorption value of the observation group was lower than that of the control group ( P<0.05). At 12 months after repair, the bone resorption values of both groups were higher than those of 6 months after repair (all P<0.05), and there was no statistical significance in the bone resorption values of the two groups at 2 months after repair ( P>0.05). At 12 months after implantation, there was no significant difference in the success rate between the two groups ( P>0.05). The total incidence of complications in the observation group (6.98%, 3/43) was lower than that in the control group (27.91%, 12/43) ( P<0.05). Conclusions:Immediate repair and delayed repair are effective in the restoration of the anterior tooth region in elderly patients with periodontal disease. Compared with delayed repair, immediate repair can reduce the alveolar bone absorption of patients, improve the soft tissue health around the implant, have better aesthetic effects, and reduce the risk of complications.

Objective To investigate the impact of different application methods of tissue compensators(bolus)on the skin dose delivered to the chest wall following radical mastectomy for breast cancer.Methods A retrospective analysis was conducted on 60 female patients who underwent radical mastectomy and required chest wall radiotherapy at the hospital between January 2023 and March 2025.The Pinnacle3 9.10 radiotherapy planning system(TPS)was utilized to design two VMAT dual semi-arc radiotherapy plans for each patient,with a prescribed target dose of 50 Gy delivered in 2 Gy fractions over 25 sessions.In Plan 1,a Bolus was applied and optimized during the first 15 fractions,and subsequently removed for the remaining 10 fractions without re-optimization.The sub-field configuration and dose weighting from the initial optimization were retained,and only dose recalculations were performed.The final treatment plan combined both the Bolus-included and Bolus-excluded phases.In contrast,Plan 2 involved the application and optimization of Bolus during the first 15 fractions,followed by its removal and re-optimization of the plan for the last 10 fractions.The two optimized plans were then combined for the overall treatment delivery.Data from the two plan groups were analyzed using a paired sample t-test with SPSS 29.0 software.Results There was a statistically significant difference(P＜0.05)in skin Dmean,V52.5,and V55;heart Dmean,V5,V30,and V40;affected lung Dmean,V5,and V20;PRVcord Dmean and Dmax;healthy breast Dmean,V5,and V10;affected humeral head Dmean and V30;as well as PTV Dmean,V50,V55,D2％,D98％,CI,and MU.Moreover,the dose distribution on the target layer and the DVH curves showed marked differences.However,no statistically significant difference was observed in PTV HI(P=0.125).Conclusion The combination of the two optimized plans,consisting of 15 fractions with bolus and 10 fractions without bolus,more accurately reflects the dose distri-bution within the planned target area and organs at risk,thereby providing enhanced protection for the patient's chest wall skin.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.