This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province, and to analyze the genotypes and hematological phenotypes. METHODS: Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province, whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations. The mutations of β-globin gene clusters were confirmed by polymerase chain reaction (PCR) and Sanger DNA sequencing technology. RESULTS: The 3.5 kb deletion in β-globin gene cluster (NC_000011.10: g. 5224302-5227791del3490bp) was detected in 4 patients' samples, of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation. These 2 patients displayed moderate anemia phenotype, while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype. CONCLUSION Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia, compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia. In areas with a high incidence of thalassemia, suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.
Humans ; beta-Globins/genetics* ; Multigene Family ; beta-Thalassemia/genetics* ; Mutation ; Genotype ; Sequence Deletion ; Phenotype ; Male ; Female

OBJECTIVE: To explore the efficacy and safety of Juan Bi Pill (JBP) in treatment of active rheumatoid arthritis (RA). METHODS: From February 2017 to May 2018, 115 participants from 4 centers were randomly divided into JBP group (57 cases) and placebo group (58 cases) in a 1:1 ratio using a random number table method. Participants received a dose of JBP (4 g, twice a day, orally) combined with methotrexate (MTX, 10 mg per week) or placebo (4 g, twice a day, orally) combined with MTX for 12 weeks. Participants were required with follow-up visits at 24 and 48 weeks, attending 7 assessment visits. Participants were undergo disease activity assessment 7 times (at baseline and 2, 4, 8, 12, 24, 48 weeks) and safety assessments 6 times (at baseline and 4, 8, 12, 24, 48 weeks). The primary endpoint was 28-joint Disease Activity Score (DAS28-ESR and DAS28-CRP). The secondary endpoints included American College of Rheumatology (ACR) criteria for 20% and 50% improvement (ACR20/50), Health Assessment Questionnaire Disability Index (HAQ-DI), clinical disease activity index (CDAI), visual analog scale (VAS), Short Form-36 (SF-36) score, Medial Outcomes Study (MOS) sleep scale score, serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count, swollen joint count, and morning stiffness. The adverse reactions were observed during the treatment. RESULTS: After 12 weeks of treatment, DAS28-ESR and DAS28-CRP scores in both groups were lower than before treatment (both P<0.01), while the remission rate of DAS28-ESR and DAS28-CRP and low disease activity of JBP group were higher than those in the placebo group (both P<0.01). JBP demonstrated better efficacy on ACR20 and ACR50 compliance rate at 12 and 48 weeks comparing to placebo (all P<0.05). The CDAI and HAQ-DI score, pain VAS and global VAS change of RA patients and physicians, the serum ESR and CRP levels, and the number of tenderness and swelling joints were lower than before treatment at 4, 8, 12, 24, 48 weeks in both groups (P<0.05 or P<0.01), while the reduction of above indices in the JBP group was more obvious than those in the placebo group at 12 weeks (ESR and CRP, both P<0.05) or at 12 and 48 weeks (all P<0.01). There was no difference in adverse reactions between the 2 groups during treatment (P=0.75). CONCLUSION JBP combined with MTX could effectively reduce disease activity in patients with RA in active stage, reduce the symptoms of arthritis, and improve the quality of life, while ensuring safety, reliability, and fewer adverse effects. (Trial Registration: ClinicalTrials.gov, No. NCT02885597).
Humans ; Arthritis, Rheumatoid/drug therapy* ; Methotrexate/adverse effects* ; Female ; Double-Blind Method ; Male ; Middle Aged ; Treatment Outcome ; Drugs, Chinese Herbal/adverse effects* ; Drug Therapy, Combination ; Adult ; Antirheumatic Agents/adverse effects* ; Aged

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Sulfur dioxide(SO2)is involved in regulating various physiological processes of blood vessels,such as maintaining normal vascular structure,regulating vascular tension,controlling blood pressure,inhibiting vascular cell proliferation,regulating apoptosis and autophagy.In pathophysiological conditions such as hypertension,pulmonary hypertension and atherosclerosis,SO2 plays a protective role in pathological changes through different molecular mechanisms.In this paper,we will review the endogenous SO2 production and metabolism,vascular biological effects and its regulation on blood vessels.

Hydrogen sulfide(H2S)is an emerging endogenous neuromodulator that holds significant potential in the realm of neurological diseases.Its role encompasses reducing neuronal damage,inhibiting excessive activation of striatal astrocytes,and regulating cerebrovascular function,among other physiopathological pathways.Conversely,microRNAs(miRNAs)are widely recognized as pivotal regulators of neurological diseases.They primarily target the 3'untranslated region of the target gene mRNA,impeding mRNA translation and hindering its expression to impart neuroprotective effects.Recent findings have underscored the crucial involvement of H2S and miRNAs in the pathogenesis of various neurological disorders such as Parkinson's disease,stroke,and spinal cord diseases,thereby garnering significant attention.This paper comprehensively summarizes the protective effects arising from the interplay between H2S and miRNAs in neurological diseases,while also delving into the potential therapeutic efficacy they hold for such conditions.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

ObjectiveThe pyrolysis temperature range of Scutellariae Radix（SR） and wine-processed SR（WSR） was studied by thermal analysis technique， and the quality difference in the contents of main components and fingerprint of WSR from different producing areas was compared， in order to provide a basis for the production process and quality evaluation of WSR. MethodThermal analysis technology was used to analyze the pyrolysis properties of SR， WSR， extract of SR and main components（baicalin， baicalein， wogonoside and wogonin）， so as to determine the optimal processing temperature range of WSR. Then combined analytic hierarchy process（AHP）， criteria importance through intercrieria correlation（CRITIC） and weighting evaluation， the optimal processing time was optimized. Based on the optimal conditions， SR from Shanxi， Hebei and Gansu provinces were processed. Ultra performance liquid chromatography（UPLC） was employed to establish the fingerprint of WSR， and the similarity analysis and common peak identification were carried out. At the same time， the contents of seven representative components（baicalin， chrysin-7-O-glucuronide， oroxylin A-7-O-β-D-glucuronide， wogonoside， baicalein， wogonin and oroxylin） were determined， then the quality differences of SR and WSR from different origins were compared. Based on the contents of seven active components， different batches of WSR were classified by hierarchical cluster analysis（HCA）， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the variable importance in the projection（VIP） value>1 was used to screen the differential components of each group. ResultThe optimum processing temperature of WSR was 190-200 ℃， and 190 ℃ for 8 min was selected as the frying process. The similarities between the fingerprints of SR and their control fingerprint were≥0.97， and the similarities between the fingerprints of WSR and their control fingerprint were≥0.98， suggesting that the processing could make the quality of decoction pieces consistent to a certain extent. The content determination results showed that the content of glycosides in SR from Gansu was lower than that from the other 2 producing areas， but the content of aglycones was higher. After being processed with wine， the content of 7 index components in SR from all producing areas decreased slightly， and the content of sample from Gansu province decreased greatly. The results of multivariate statistical analysis and discriminant analysis showed that wogonoside was the key ingredient for distinguishing WSR from different producing areas. ConclusionThis study determined the best processing technology of WSR and screened out the different component of wogonoside to distinguish between different origins of WSR， which can provide reference for the quality evaluation of WSR.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the digestive tract system, which is induced by multiple factors, involving multiple genes and complicated mechanism. Its incidence and mortality rank fourth and second respectively in China, and accounting for more than 85% of primary liver cancers. Tumor immune microenvironment (TIME), plays a critical role in determining the tumor progression and treatment outcomes, making it become a hotspot in current studies. Summarising the previous studies, it is found that the progression of HCC is significantly influenced by the TIME and its complex interactions. TIME consists of various cellular and non-cellular components, such as myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs), innate lymphoid cells (ILCs), as well as growth factors, proteolytic enzymes, and extracellular matrix proteins. Due to long-term exposure to bacterial components carried by the portal vein, food-derived antigens, and a large amount of foreign antigenic substances, the microenvironment of liver exhibits a certain degree of immune suppression to resist excessive inflammation caused by the non-pathogenic intestinal environment. Besides, the inhibitory immune microenvironment shaped by tumor cells which induces changes in the phenotype and function of immune cells, and attenuates the cytotoxic capabilities of immune system. Meanwhile, the regulation of immune cell metabolism is crucial for anti-tumor immune response. Abnormal metabolites of liver cancer microenvironment and intestinal flora metabolites regulate the remodeling of immune microenvironment and the progression in liver cancer. Normally, the cancer immune cycle functions effectively to remove tumor cells, while the immunosuppressive, exhausted T cells and metabolic disorders of the TIME leads to defects in the cancer immunity cycle and promotes to tumor progression. Furthermore, during the processes of rapid proliferation and differentiation, tumor cells alter their metabolic status through “metabolic reprogramming”, allowing them to compete with anti-tumor immune cells for vital nutrients including glucose, lipids, and nucleotides. At the same time, the abnormal consumption of metabolites leads to local hypoxia, lower pH levels, and the accumulation of metabolic products, which in turn suppress the proliferation and effector functions of immune cells, ultimately facilitating immune evasion and tumor progression. According to the above, local immune imbalance and metabolic disorders in the liver collectively shape the unique microenvironment of HCC, resulting in the accumulation of immunosuppressive cytokines, extracellular matrix and abnormal metabolites. These factors induce abnormal tumor angiogenesis, recruitment of immunosuppressive cells, reduce T-cell infiltration, and diminish anti-tumor function, which accelerates the progression of HCC and immune escape. Currently, there are still remarkable limitations in the clinical treatment methods and outcomes for HCC, while immunotherapy offers a new strategy. The advantages of immunotherapy demonstrate relatively higher specificity and fewer side effects compared to traditional treatment methods such as surgery, radiotherapy, and chemotherapy. Up to now, more and more evidence has been uncovered that liver cancer immunotherapy is closely related to TIME. Targeting the TIME of HCC provides a new perspective into a deeper understanding of the mechanisms of immunotherapy resistance and the development of new immunotherapy approaches. However, single immunotherapy has not shown satisfactory results in improving the prognosis of HCC patients. At present, dual immune checkpoint inhibitors or their combination with existing therapies are being widely explored in clinical studies, hoping to overcome the limitations of HCC therapy. Therefore, this review summarizes the composition of immunosuppressive microenvironment in liver cancer and metabolic regulation, and further discusses clinical therapeutic strategies by targeting microenvironment remodeling for the treatment of liver cancer, which provides new avenues for tumor immunotherapy.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.