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.

Objective To investigate the mechanism by which long non-coding RNA(lncRNA)AI662270 regulates insulin resistance in adipocytes in aging mice.Methods(1)Twenty male C57BL/6 mice were randomly divided into youth(4-month-old)group and aged(18-month-old)group(n=10).Mice in youth group were raised to 4 months of age and euthanized by orbital exsanguination under urethane anesthesia,while aged mice were euthanized at 18 months using the same sacrifice method.Epididymal white adipose tissue(eWAT)and liver tissue were rapidly dissected.Western blotting was employed to detect the protein expression levels of tumor suppressor gene 1(p16ink4a)and cyclin-dependent kinase inhibitor p21(p21kip1),RT-qPCR was used to measure the expression of 4 differentially expressed lncRNAs(C4a,AI662270,BATE1 and Gm29719).Mouse embryonic fibroblasts(3T3-L1)were cultured and divided into a normal control group(no treatment after induced differentiation into mature adipocytes)and a senescence model group[doxorubicin(ADR)-treated group;0.2 μmol/L ADR was used to induce senescent adipocytes].β-galactosidase staining was performed to assess adipocyte senescence.RT-qPCR was applied to evaluate the expression of AI662270 and senescence markers(p16ink4a,p21kip1,p53),while Western blotting was utilized to detect the expression levels of phosphorylated H2A histone family member X(γ-H2AX),p16ink4a,and p21kip1 proteins.(2)Hexokinase method was adopted to measure glucose content in mouse serum and 3T3-L1 adipocyte culture medium.RT-qPCR was performed to analyze mRNA expression levels of insulin sensitivity-related gene protein kinase B(Akt),insulin receptor substrate 1(IRS1),phosphatidylinositol 3 kinase(PI3K)and glucose transporter 4(GLUT4)in mouse eWAT and adipocytes.Western blotting was conducted to determine the protein expression levels of IRS 1,PI3K,Akt,and p-Akt.(3)Spearman correlation analysis was applied to examine the correlation between AI662270 expression levels and IRS1/PI3K mRNA expression levels.A low-expression model of AI662270 in senescent adipocytes was constructed,and RT-qPCR was used to verify the knockdown efficiency.Hexokinase method was employed to assess glucose content in the cell culture medium of senescent adipocytes after AI662270 knockdown.RT-qPCR was performed to measure the mRNA expressions of Akt,IRS1,IRS2,and PI3K,while Western blotting was utilized to detect the expressions levels of Akt and p-Akt proteins.(4)Bioinformatics analysis was performed to predict downstream target genes of AI662270 and their binding sites.RT-qPCR and Western blotting were subsequently applied to validate the expression of these downstream target genes following AI662270 knockdown.Results(1)Compared with youth group,the protein expression levels of p16ink4a and p21kip1 in eWAT of aged mice were significantly increased(P＜0.05).Additionally,the expression levels of C4a,AI662270,BATE1,and Gm29719 in both eWAT and liver tissues were significantly increased in aged group(P＜0.05).β-galactosidase staining revealed enhanced blue-green coloration and enlarged,flattened cellular morphology in ADR-treated senescent adipocytes compared with normal control group.Compared with normal control group,ADR-treated senescent adipocytes significantly increased the mRNA expression levels of AI662270,p16ink4a,and p21kip1,and significantly elevated protein expression levels of γ-H2AX,p16ink4a,and p21kip1(P＜0.05).(2)Serum glucose content was significantly higher in aged group mice compared with youth group(P＜0.01),and glucose content in the adipocyte culture medium in ADR group was significantly increased(P＜0.05).The expression levels of IRS1 and PI3K in eWAT in aged group were significantly reduced compared with youth group(P＜0.01).Compared with normal control group,the expression levels of IRS 1 and PI3K in adipocytes in ADR-treated group were also significantly reduced(P＜0.05).(3)Spearman correlation analysis demonstrated that the expression level of AI662270 was negatively correlated with the mRNA expression levels of IRS1 and PI3K(P＜0.05).RT-qPCR showed that AI662270 expression level was significantly reduced in the siAI662270-transfected senescent adipocytes compared with siNC group(P＜0.05),indicating the low expression model of aged adipocytes AI662270 was successfully constructed.Hexokinase assay results showed that glucose content in the cell culture medium was significantly reduced after the AI662270 was knocked down by senescent adipocytes(P＜0.05).Furthermore,the mRNA expression levels of IRS1,IRS2 and PI3K(P＜0.05)and the p-Akt/Akt ratio in senescent adipocytes was significantly increased after knockdown of AI662270(P＜0.01).(4)Bioinformatics analysis predicted miR-3073b-3p as a downstream target gene of AI662270,and heme oxygenase 1(Hmox1)was identified as a target molecule of miR-3073b-3p.The expression level of miR-3073b-3p in senescent adipocytes in siAI662270 group was significantly increased,while the mRNA and protein expression level of Hmox1 were significantly decreased compared with siNC group(P＜0.01).Conclusions Aging significantly increases the expression of AI662270 in eWAT of mice,and the expression of AI662270 was negatively correlated with insulin sensitivity.AI662270 knockdown can reduce glucose content in senescent adipocyte culture medium,upregulate the expression of IRS1 and PI3K,and increase insulin sensitivity in senescent adipocytes,which may be mediated through the AI662270/miR-3073b-3p/Hmox1 pathway.

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.

OBJECTIVES: To characterize fine particulate matter (PM _2.5)-bound polycyclic aromatic hydrocarbons (PAHs) emitted from different cooking fumes and their exposure routes and assess their health-associated impact to provide a reference for health risk prevention from PAH exposure across different age and sex groups. METHODS: Sixteen PM _2.5-bound PAHs emitted from 11 cooking styles were analyzed using GC-MS/MS. The health hazards of these PAHs in the Handan City population (stratified by age and sex) were predicted using the incremental lifetime cancer risk ( ILCR) model. The respiratory deposition doses ( RDDs) of the PAHs in children and adults were calculated using the PM _2.5 deposition rates in the upper airway, tracheobronchial, and alveolar regions. RESULTS: The total concentrations of PM _2.5-bound PAHs ranged from 61.10 to 403.80 ng/m ³. Regardless of cooking styles, the ILCR _total values for adults (1.23 × 10 ^-6 to 3.70 × 10 ^-6) and older adults (1.28 × 10 ^-6 to 3.88 × 10 ^-6) exceeded the acceptable limit of 1.00 × 10 ^-6. With increasing age, the ILCR _total value first declined and then increased, varying substantially among the population groups. Cancer risk exhibited particularly high sensitivity to short exposure to barbecue-derived PAHs under equivalent body weights. Furthermore, barbecue, Sichuan and Hunan cuisine, Chinese cuisine, and Chinese fast food were associated with higher RDDs for both adults and children. CONCLUSION ILCR _total values exceeded the acceptable limit for both females and males of adults, with all cooking styles showing a potentially high cancer risk. Our findings serve as an important reference for refining regulatory strategies related to catering emissions and mitigating health risks associated with cooking styles.
Humans ; Polycyclic Aromatic Hydrocarbons/analysis* ; Cooking/methods* ; Male ; Female ; Particulate Matter/analysis* ; Adult ; Child ; Middle Aged ; Air Pollutants/analysis* ; Adolescent ; Air Pollution, Indoor/analysis* ; Young Adult ; Child, Preschool ; Aged ; China ; Inhalation Exposure ; Age Factors ; Sex Factors ; Cities ; Infant

ObjectiveTo explore the main mechanism of self-precipitation formed during the decoction of Sinitang（SNT）， and to provide a research basis for exploring the differences in the toxic and effective components of this compound. MethodsThe average precipitation yields of SNT， Glycyrrhizae Radix et Rhizoma（GRR）-Aconiti Lateralis Radix Praeparata（ALRP） decoction（GF）， ALRP-Zingiberis Rhizoma（ZR） decoction（FJ）， GRR-ZR decoction（GJD）， ALRP decoction（FZ）， ZR decoction（GJ） and GRR decoction（GC） were determined. The four main self-precipitation samples of SNT， GF， FZ and GC were physically characterized by particle size， scanning electron microscopy（SEM）， pH， total dissolved solids（TDS）， conductivity， and Fourier transform infrared spectroscopy（FT-IR） analysis. The chemical compositions of SNT decoction and its different phases was identified by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS） for SNT， SNT self-precipitation and SNT supernatant， and the contents of its main toxic and effective components were determined by high performance liquid chromatography（HPLC）. ResultsPrecipitation yield results of the 7 samples of SNT decoction and single decoction showed that SNT had the highest self-precipitation yield. The formation of SNT self-precipitation was mainly related to the reaction between ALRP and GRR components to form complexes， and FT-IR showed that GRR had the greatest influence on the formation of self-precipitation. A total of 110 components were identified in the SNT decoction， including 100 components in the SNT self-precipitation and 106 components in the SNT supernatant. And quantitative results of the main toxic and effective components revealed that the reaction between ALRP and GRR components formed complexes， resulting in the following content hierarchy for free components：SNT decoctionsupernatantself-precipitation， these components included free liquiritin， benzoylmesaconine， benzoylaconitine， benzoylhypacoitine， liquiritigenin， aconitine， hypoaconitine， isoliquiritigenin and ammonium glycyrrhizinate. ConclusionSNT exhibits spontaneous precipitation during compound decoction， with GRR exerting the greatest influence on its formation. This suggests GRR plays a significant role in the detoxification of SNT. The differences in the self-precipitated toxic-effective components of SNT compound decoction primarily manifest as changes in component content， reflecting the characteristics of SNT "deposition in vitro and sustained release in vivo" and the importance of "administered at draught" in the clinical application of SNT.

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.

OBJECTIVE: Tumor-derived exosomes (TDEs) play crucial roles in intercellular communication. Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis. Jiedu recipe (JR), a traditional Chinese medicinal formula, has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown. METHODS: Animal experiments were performed to investigate the metastasis-preventing effects of JR. Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR. TDEs were assessed using nanoparticle tracking analysis (NTA) and Western blotting (WB). Exosomes derived from normoxic or hypoxic HCC cells (H-TDEs) were collected to establish premetastatic mouse models. JR was intragastrically administered to evaluate its metastasis-preventive effects. WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy. Bioinformatics analysis, WB, NTA, and immunofluorescence staining were used to identify the active components and potential targets of JR. RESULTS: JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis. It inhibited the release of exosomes from tumor cells under hypoxic condition. JR treatment promoted both lysosomal acidification and suppressed secretory autophagy, which were dysregulated in hypoxic tumor cells. Quercetin was identified as the active component in JR, and the epidermal growth factor receptor (EGFR) was identified as a potential target. Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB (TFEB). Hypoxia-impaired lysosomal function was restored, and secretory autophagy was alleviated by quercetin treatment. CONCLUSION JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release, restoring lysosomal function, and suppressing secretory autophagy. Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling. Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion. Please cite this article as: Jia WT, Xiang S, Zhang JB, Yuan JY, Wang YQ, Liang SF, Lin WF, Zhai XF, Shang Y, Ling CQ, Cheng BB. Jiedu recipe, a compound Chinese herbal medicine, suppresses hepatocellular carcinoma metastasis by inhibiting the release of tumor-derived exosomes in a hypoxic microenvironment through the EGFR-TFEB signaling pathway. J Integr Med. 2024; 22(6): 697-709.
Exosomes/drug effects* ; Animals ; Carcinoma, Hepatocellular/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Liver Neoplasms/pathology* ; Tumor Microenvironment/drug effects* ; Mice ; Humans ; Cell Line, Tumor ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Male ; Mice, Nude

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Party building and leadership,keeps the right track and acts as a dynamic source of the innovative develop-ment of clinical medical humanities.To give full play to the guidance of Party building and leadership,it is imperative that we implement the"Six Persistences",whose connotation is persisting in putting the people first,maintaining self-confidence and standing on our own feet,upholding fundamental principles and breaking new ground,adopting a problem-oriented approach,ap-plying systems thinking,and maintaining a global vision.A good command of the worldview and methodology of Xi Jinping Thought on Socialism with Chinese Characteristics for a New Era anchors the direction for the construction of clinical medical hu-manities.Trough political,ideological and organizational guidance,institutional guarantee and dual integration and promotion of Party building and discipline deepening,the constructive mechanism can be improved,humanistic sentiments cultivated,profi-cient teams built,a sound system established and new patterns incubated.High-quality Party building and leadership contributes to the progressive development of clinical medical humanities construction.

Cardiac cephalalgia is a rare disease caused by underlying coronary artery disease that presents as headache with or without chest symptoms.Headache symptoms are often caused by referred pain,increased intracranial pressure and release of large amounts of pain-causing neurochemicals due to myocardial ischemia,and cortical hypoperfusion.Due to the low overall prevalence of the disease,the lack of chest pain typical of coronary heart disease,and the fact that it may be difficult to distinguish from headaches caused by neurological diseases,accurate diagnosis and treatment of the disease are often delayed.We report a case of acute coronary syndrome with headache only.Revascularization was achieved through percutaneous coronary intervention therapy,followed by standard secondary prevention pharmacotherapy.Follow-up six months postoperatively showed a significant improvement in exercise tolerance,with no further headache episodes.The purpose is to improve the understanding of patients with cardiac cephalalgia,with a view to early identification and timely intervention,and ultimately improve the symptoms and prognosis.