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*

OBJECTIVES: To investigate the current status and influencing factors of quality of life in children and adolescents with type 1 diabetes (T1DM) in Xinjiang. METHODS: A convenience sampling method was used to select 259 children with T1DM and their primary caregivers who attended three tertiary hospitals in Xinjiang from January 2023 to February 2024. The Pediatric Quality of Life Inventory^TM Version 4.0 Generic Core Scales (PedsQL^TM4.0) and Pediatric Quality of Life Inventory^TM Version 3.2 Diabetes Module (PedsQL^TM3.2-DM) were used to assess the quality of life of the children. Information on family demographics, caregiver burden, and caregiving ability was also collected. Multiple linear regression analysis was employed to identify factors associated with the quality of life of the children. RESULTS: The scores for PedsQL^TM4.0 and PedsQL^TM3.2-DM were 77±16 and 71±16, respectively. Both were negatively correlated with caregiver burden (P<0.05) and positively correlated with caregiving ability (P<0.05). Multiple linear regression analysis indicated that caregiver burden, caregiving ability, family income, and parent-child relationship were significantly associated with generic quality of life (P<0.05), whereas caregiver burden, caregiving ability, disease duration, place of residence, and glycated hemoglobin level were significantly associated with diabetes-specific quality of life (P<0.05). CONCLUSIONS The overall quality of life of children and adolescents with T1DM in Xinjiang is relatively low. The quality of life is influenced by a combination of factors including family caregiver burden, caregiving ability, family income, parent-child relationship, disease duration, place of residence, and glycated hemoglobin level. Strategies to improve quality of life should consider the combined impact of individual disease characteristics and family factors.
Humans ; Quality of Life ; Diabetes Mellitus, Type 1/psychology* ; Adolescent ; Child ; Male ; Female ; Caregivers/psychology* ; Child, Preschool ; Linear Models

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Oligodendrocyte lineage cells, including oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs), are essential in establishing and maintaining brain circuits. Autophagy is a conserved process that keeps the quality of organelles and proteostasis. The role of autophagy in oligodendrocyte lineage cells remains unclear. The present study shows that autophagy is required to maintain the number of OPCs/OLs and myelin integrity during brain aging. Inactivation of autophagy in oligodendrocyte lineage cells increases the number of OPCs/OLs in the developing brain while exaggerating the loss of OPCs/OLs with brain aging. Inactivation of autophagy in oligodendrocyte lineage cells impairs the turnover of myelin basic protein (MBP). It causes MBP to accumulate in the cytoplasm as multimeric aggregates and fails to be incorporated into integral myelin, which is associated with attenuated endocytic recycling. Inactivation of autophagy in oligodendrocyte lineage cells impairs myelin integrity and causes demyelination. Thus, this study shows autophagy is required to maintain myelin quality during aging by controlling the turnover of myelin components.
Animals ; Autophagy/physiology* ; Oligodendroglia/metabolism* ; Myelin Sheath/physiology* ; Aging/pathology* ; Myelin Basic Protein/metabolism* ; Cell Lineage/physiology* ; Mice ; Oligodendrocyte Precursor Cells ; Mice, Inbred C57BL ; Brain/cytology* ; Cells, Cultured ; Cell Count

Objective:To explore the efficacy and adverse reactions of nimotuzumab combined with induction chemotherapy (IC) based on albumin-bound paclitaxel plus cisplatin (TP regimen) for patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC).Methods:Clinical data were collected from 65 patients with LA-HNSCC (stages Ⅲ/Ⅳ A/Ⅳ B; excluding nasopharyngeal carcinoma) who received 2-3 cycles of IC followed by concurrent chemoradiotherapy (CRT) in the Second Hospital of Dalian Medical University from January 2018 to June 2022. Based on the IC regimen, these patients were categorized into a nimotuzumab combined with TP (Nimo-TP) group ( n = 34) and a TP group ( n = 31), and their short-term efficacy [i.e., the objective response rate (ORR)], survival outcomes [e.g., overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS)], and adverse reactions were compared. Additionally, factors affecting their survival outcomes were analyzed. Results:There were statistically significant differences in 1- and 2-year DMFS between both groups (90.4% vs. 69.5%, 90.4% vs. 66.0%, χ2=1.81, P < 0.05), so did the ORRs after IC and CRT of both groups (after IC: 67.6% vs. 41.9%, χ2=4.34, P = 0.037; after CRT: 88.2% vs. 67.7%, χ2=4.03, P = 0.045). However, there was no statistically significant difference in the 2-year OS, PFS, and LRFS between both groups ( P > 0.05). Multivariate analysis revealed that nimotuzumab combined with TP-based IC served as an independent prognostic factor for DMFS ( HR = 0.27, 95% CI: 0.07-0.97, P = 0.045), while complete/partial response after IC acted as an independent prognostic factor for both PFS and local relapse-free survival ( HR = 0.36, 95% CI: 0.17-0.76, P = 0.008; HR = 0.28, 95% CI: 0.11-0.69, P = 0.006). Notably, adding nimotuzumab did not aggravate the adverse reactions in the patients during IC and CRT( P > 0.05). Conclusions:Nimotuzumab combined with TP-based induction chemotherapy followed by CRT significantly improved the DMFS of LA-HNSCC patients, exhibiting high safety. However, such therapy failed to significantly improve their OS, PFS, and LRRFS, and, thus, further research is required.

Objective:To explore the application of C-reactive protein(CRP) to prealbumin (PA) ratio(CRP/PA) for diagnosis and prognosis evaluation of sepsis.Methods:By a retrospective study, a total of 95 sepsis patients (sepsis group) and 100 local infection patients(non-sepsis group) treated in Dongying People′s Hospital from September 2021 to September 2022 were enrolled. Sepsis patients were divided into survival group(57 cases) and death group (38 cases) according to the 28-day outcome. The clinical data were collected and CRP/PA was calculated. Multivariate Logistic regression and Cox regression were used to analyze the relationship between various indicators and the occurrence and prognosis of sepsis, and receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic and prognostic value of CRP/PA for sepsis. Kaplan-Meier survival analysis was used to evaluate the prognostic value of different CRP/PA ratios for patients with sepsis.Results:The systolic blood pressure, diastolic blood pressure, prealbumin were lower and heart rate, respiratory rate, CRP, CRP/PA, procalcitonin were higher in the sepsis group compared to the non-sepsis group: (117.27 ± 11.65) mmHg (1 mmHg = 0.133 kPa) vs. (123.26 ± 10.71) mmHg, (69.42 ± 8.58) mmHg vs. (75.44 ± 6.53) mmHg, (174.09 ± 24.77) g/L vs. (207.13 ± 34.31) g/L, (97.87 ± 12.73) bpm vs. (86.90 ± 10.19) bpm, 22.0(20.00, 25.00) times/min vs. 21.00(19.00, 23.00) times/min, (93.96 ± 19.64) mg/L vs. (77.56 ± 22.54) mg/L, 0.54(0.44, 0.65) vs. 0.37(0.28, 0.46), 3.35(2.16, 4.17) μg/L vs. 1.52(0.81, 2.16) μg/L, there were statistical differences ( P<0.05). Multivariate Logistic regression analysis showed that CRP/PA and procalcitonin were risk factors for sepsis ( P<0.05). The results of ROC curve showed that the area under the curve (AUC) of CRP/PA in diagnosis of sepsis was 0.821, the specificity and sensitivity was 76.0% and 93.7%, respectively. The diastolic blood pressure, prealbumin, neutrophil were higher and the heart rate, respiratory rate, CRP, CRP/PA, lymphocytes, procalcitonin were lower in the survival group compared to the death group: (71.76 ± 8.86) mmHg vs. (67.86 ± 8.10) mmHg, (181.46 ± 24.35) g/L vs. (163.05 ± 21.28) g/L, (63.46 ± 9.88) × 10 9/L vs.(57.13 ± 8.64) × 10 9/L, (95.68 ± 13.48) times/min vs. (101.16 ± 10.88) times/min, 22.00(19.50, 24.00) times/min vs. 24.00(20.00, 28.00) times/min, (88.09 ± 19.35) mg/L vs. (102.76 ± 16.75) mg/L, 0.46(0.41, 0.58) vs. 0.63(0.55, 0.72), 21.00(16.00, 30.00) ×10 9/L vs. 29.50(18.00, 37.30) ×10 9/L, 2.94(2.10, 3.97) μg/L vs. 3.82(2.21, 4.77) μg/L, there were statistical differences ( P<0.05). Multivariate Cox regression analysis showed that CRP/PA and procalcitonin were independent risk factors for the prognosis of sepsis ( P<0.05). The AUC of CRP/PA in predicting the prognosis of sepsis was 0.827, the specificity and sensitivity was 92.1% and 63.8%, respectively. Grouped by the cut-off of CRP/PA (0.48), the 28-day mortality rate of patients in the CRP/PA>0.48 was significantly higher than that of patients in the CRP/PA≤0.48, there was statistical difference ( P<0.01). Conclusions:CRP/PA ratio can be used as an index for diagnosis and prognosis evaluation of sepsis.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

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.