The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

Objective To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T(UBE2T)on radiosensitivity of hepatocellular carcinoma(HCC).Methods Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector,and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay.The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice,and tumor growth following irradiation were recorded.The xenografts were collected for analyzing infiltration of CD4+T cells and regulatory T cells(Tregs)using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting.The correlations of UBE2T expression with immune cell infiltration,glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database,and the results were verified in a co-culture system of Hepa1-6 cells and Tregs.Results UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models(especially in C57BL/6 mice).CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells,T follicular helper cells,M2 macrophages,monocytes,lymphocytes and Tregs in HCC.The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA,and irradiation increased infiltration of CD4+T cells and Tregs in the tumor microenvironment.Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration.GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC.In the cell co-culture system,UBE2T overexpression significantly enhanced lactate production,proliferation and immunosuppressive functions of Tregs.Conclusion A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

Objective:To compare clinical efficacy and safety of peripheral to central pruning of apocrine sweat glands versus along small incision of apocrine sweat glands in the treatment of axillary bromhidrosis.Methods:A prospective randomized controlled study method was used to recruit patients with armpit odor admitted to the Department of Aesthetic and Plastic Surgery, Affiliated Hospital of Zunyi Medical University from June to October 2022. The patients were divided into the experimental group (underwent peripheral to central pruning of apocrine sweat glands with small incision of axillary fold under direct view) and the control group (apocrine sweat glands were cut off along the direction of small incisions) by randomization. The occurrence of postoperative complications such as hematoma, infection, skin necrosis, delayed incision healing, scar and skin contracture were observed in both groups, and the incidence rate was calculated. The surgical effect was evaluated 6 months after the operation, and the number of cured, markedly effective, and ineffective sides was counted, and the cure rate and effective rate were calculated; the satisfaction was investigated and divided into two options: satisfactory and dissatisfied, and the satisfaction rate was calculated. Count data were analyzed using the chi-square test. P<0.05 indicated that the difference was statistically significant. Results:A total of 52 patients were recruited. Experimental group, 26 patients (52 side), 6 male, 20 women, aged 18-31 years, mean of 22 years; control group, 26 patients (52 side), 6 male, 20 women, aged 18-47 years, mean of 21 years. The incidence of postoperative complications in the experimental group was 3.85% (2 / 52), which was lower than 19.23% (10/52) of the control group, with statistically significant difference ( χ2=3.98, P=0.046), in which the flap necrosis, local contracture, scarring and delayed incision healing were better than the control group. The postoperative response rate in both groups was 100%(52/52), but the cure rate in the experimental group was higher than the control group [96.15% (50/52) vs. 80.77% (42/52)], with a significant difference ( χ2=6.03, P=0.014). The satisfaction rate of the experimental group was 96.15% (50/52), higher than the 82.69% (43/52) of the control group, and the difference was statistically significant ( χ2=4.92, P=0.026). Conclusion:Compared with the traditional small incision of peripheral to central pruning method and the traditional small incision of apocrine sweat glands method, the cure rate of the former is higher, which can effectively protect the skin flap dermis and subdermal vascular network around the incision, reduce postoperative skin necrosis and scar, and improve patient satisfaction.

Objective To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T(UBE2T)on radiosensitivity of hepatocellular carcinoma(HCC).Methods Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector,and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay.The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice,and tumor growth following irradiation were recorded.The xenografts were collected for analyzing infiltration of CD4+T cells and regulatory T cells(Tregs)using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting.The correlations of UBE2T expression with immune cell infiltration,glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database,and the results were verified in a co-culture system of Hepa1-6 cells and Tregs.Results UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models(especially in C57BL/6 mice).CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells,T follicular helper cells,M2 macrophages,monocytes,lymphocytes and Tregs in HCC.The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA,and irradiation increased infiltration of CD4+T cells and Tregs in the tumor microenvironment.Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration.GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC.In the cell co-culture system,UBE2T overexpression significantly enhanced lactate production,proliferation and immunosuppressive functions of Tregs.Conclusion A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

Objective:To compare clinical efficacy and safety of peripheral to central pruning of apocrine sweat glands versus along small incision of apocrine sweat glands in the treatment of axillary bromhidrosis.Methods:A prospective randomized controlled study method was used to recruit patients with armpit odor admitted to the Department of Aesthetic and Plastic Surgery, Affiliated Hospital of Zunyi Medical University from June to October 2022. The patients were divided into the experimental group (underwent peripheral to central pruning of apocrine sweat glands with small incision of axillary fold under direct view) and the control group (apocrine sweat glands were cut off along the direction of small incisions) by randomization. The occurrence of postoperative complications such as hematoma, infection, skin necrosis, delayed incision healing, scar and skin contracture were observed in both groups, and the incidence rate was calculated. The surgical effect was evaluated 6 months after the operation, and the number of cured, markedly effective, and ineffective sides was counted, and the cure rate and effective rate were calculated; the satisfaction was investigated and divided into two options: satisfactory and dissatisfied, and the satisfaction rate was calculated. Count data were analyzed using the chi-square test. P<0.05 indicated that the difference was statistically significant. Results:A total of 52 patients were recruited. Experimental group, 26 patients (52 side), 6 male, 20 women, aged 18-31 years, mean of 22 years; control group, 26 patients (52 side), 6 male, 20 women, aged 18-47 years, mean of 21 years. The incidence of postoperative complications in the experimental group was 3.85% (2 / 52), which was lower than 19.23% (10/52) of the control group, with statistically significant difference ( χ2=3.98, P=0.046), in which the flap necrosis, local contracture, scarring and delayed incision healing were better than the control group. The postoperative response rate in both groups was 100%(52/52), but the cure rate in the experimental group was higher than the control group [96.15% (50/52) vs. 80.77% (42/52)], with a significant difference ( χ2=6.03, P=0.014). The satisfaction rate of the experimental group was 96.15% (50/52), higher than the 82.69% (43/52) of the control group, and the difference was statistically significant ( χ2=4.92, P=0.026). Conclusion:Compared with the traditional small incision of peripheral to central pruning method and the traditional small incision of apocrine sweat glands method, the cure rate of the former is higher, which can effectively protect the skin flap dermis and subdermal vascular network around the incision, reduce postoperative skin necrosis and scar, and improve patient satisfaction.

Objective:To evaluate the efficacy of Janus kinase (JAK) inhibitors in the treatment of 5 children with severe alopecia areata, especially those with complicated nail damage.Methods:A total of 5 children with severe alopecia areata were enrolled and treated with oral JAK inhibitors (tofacitinib or baricitinib). The improvement of hair loss was assessed by using the severity of alopecia tool (SALT) at 12, 24, 36, and 48 weeks after the start of treatment. For 3 children with complicated nail damage, the improvement of diseased nails and toenails was evaluated by using the modified nail psoriasis severity index after treatment. During the treatment, adverse reactions were monitored.Results:The 5 children with severe alopecia areata were aged 2 - 11 years, with the disease duration ranging from 5 to 120 months, and the treatment with JAK inhibitors lasted 24 - 48 weeks. After 12-week treatment, 2 children achieved a 50% improvement in SALT (SALT50) ; after 24-week treatment, 3 achieved SALT95, and 1 achieved SALT75 and then withdrew baricitinib for personal reasons; after 36-week treatment, 3 achieved SALT99, and then received half-dose treatment; after 48-week treatment, 1, 1, 1 and 1 patient achieved SALT99, SALT83, SALT31, and SALT0, respectively, and 2 of them experienced gradually aggravated hair loss 1 - 2 months after the start of half-dose treatment. Among the 3 children with complicated nail damage, the improvement rates of nail severity index scores were 67.5%, 45.4%, and 25% respectively, and the improvement rates of toenail severity index scores were 42.5%, 71.4%, and 5% respectively after 12-week treatment; after 48-week treatment, the improvement rate of nail severity index scores were 100%, 100%, and 50% respectively, and the improvement rate of toenail severity index scores were 96.2%, 100%, 50% respectively. During the treatment, the uric acid level increased in 2 children, and one of them was accompanied by increased serum levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol; 1 suffered from respiratory tract infections twice during the treatment, and was recovered after symptomatic treatment; there were no adverse reactions leading to drug withdrawal.Conclusion:JAK inhibitors can be used as a treatment option for severe alopecia areata in children.

Objective:To optimize the strategy of Nuss procedure with open approach via median sternotomy for pectus excavatum(PE) with congenital heart disease(CHD).Methods:25 PE patients with CHD treated in our center from January 2017 to November 2021 were reviewed and divided into two groups. The CHD surgery and open Nuss procedure with median sternotomy were performed concomitantly in 9 cases(group A), whose height of(121.7±28.0)cm, weight of(22.2±14.0)kg, age of(7.65±4.08) years old, and Haller index of 3.99±1.37. 16 cases underwent open Nuss procedure via median re-sternotomy after congenital heart surgery(group B), whose height of(130.9±27.2)cm, weight of(26.5±14.3)kg, age of(8.82±4.09) years old, and Haller index of 4.18 ± 0.97. The cardiac anatomy, cardiac function and the severity of PE of all patients were evaluated by echocardiography and computed tomography preoperatively. The preoperative gender, appearance of PE, types of associated CHD, retrosternal adhesion and the interval between open Nuss procedure and CHD surgery were collected. The details of operation, hospital stay, intraoperative adverse events, postoperative complications and follow-up were collected.Results:All the operations were accomplished successfully in 25 children. No intraoperative complications occurred. One had a postoperative wound infection in group A. The operation time of group A was significantly longer than that of group B[(3.78±1.54) h vs.(2.19±0.94) h, P<0.05]. There was no significant difference in the mechanical ventilation time between the two groups[(22.50±45.64) h vs.(4.18±1.41) h, P=0.263]. The ICU stay of group A was significantly longer than that of group B[(4.00±6.42) days vs.(1.13±0.34) days, P<0.05]. There was no significant difference in the length of hospital stay between the two groups[(16.00±15.18) days vs.(9.19±2.31) days, P=0.419]. The Nuss bar was removed in 14 cases of the two groups, with a interval of(27.9±11.25) months after open Nuss procedure, the postoperative Haller Index was 2.48±0.49. There was no difference of LVEF in postoperative and preoperative echocardiography(0.663±0.028 vs. 0.659±0.038, P=0.533). The FVC and FEV1 were significantly improved compared with before operation[(87.2±3.9)% vs.(84.1±8.2)%]. The outcome was good. Conclusion:For PE patients with CHD, one-stage or staged individualized Nuss procedure with open approach via median sternotomy can be performed after careful preoperative evaluation. A skillful median re-sternotomy and widely dissecting retrosternal adhesion between sternum and anterior wall of heart are necessary to avoid serious intraoperative complications such as massive heart bleeding and ensure good sternal elevation.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.