ObjectiveTo investigate the association and translational mechanism between the hepatotoxicity of Xianling Gubao （XLGB） and its treatment of osteoporosis based on a zebrafish model. MethodsZebrafish were randomly selected four days after fertilization （4 dpf） and exposed to different concentrations of XLGB （0.7，0.35 mg·L^-1） for 96 h. At the endpoint of the exposure， the mortality rates of zebrafish in the treatment groups of different concentrations were counted， and the "dose-toxicity" curves were plotted. The 10% sublethal concentration （LC₁₀） was calculated. The liver area， acridine orange staining， and pathological tissue sections of transgenic zebrafish ［CZ16 （gz15Tg.Tg （fabp 10a： ds Red； ela31： EGFP）］ were used as indicators to confirm the hepatic damage caused by the sublethal concentration of XLGB. By using the prednisolone （PNSL）-induced osteoporosis model of zebrafish， the anti-osteoporosis activity of XLGB was evaluated by using the area of skull stained by alizarin red and the cumulative optical density value as indicators. Then， the toxicity difference of XLGB on the liver of zebrafish in healthy and osteoporotic states was compared， and the mechanism of the translational action of the toxicity of XLGB was predicted based on network pharmacology and real-time polymerase chain reaction（Real-time PCR）. ResultsThe LC₁₀ of XLGB on zebrafish （8 dpf） was 0.7 mg·L^-1. Compared with the blank group， the sublethal concentration （LC₁₀=0.7 mg·L^-1， 1/2 LC₁₀=0.35 mg·L^-1） of XLGB induced an increase in the number of apoptosis of hepatocytes in a dose-dependent manner， and the tissue arrangement of the liver was disordered and loose. The vacuoles were obvious， and the fluorescence area of the liver was significantly reduced （P<0.01）. Compared with the blank group， the mineralized area and cumulative optical density value of zebrafish skull in the PNSL model group were significantly reduced （P<0.01）， and those in the 0.7，0.35 mg·L^-1 XLGB treatment group were significantly increased compared with the model group （P<0.01）. Most importantly， 0.7 mg·L^-1 XLGB had no significant effect on the liver of zebrafish in the osteoporosis disease model compared with the blank group. The results of network pharmacology and real-time PCR experiments showed that the toxic transformation of XLGB might be related to the differences in the expression levels of key targets， such as tumor protein 53 （TP53）， cysteine aspartic acid specific protease-3（Caspase-3）， interleukin（IL）-6， and alkaline phosphatase（ALP） in different organismal states. ConclusionUnder certain conditions， XLGB has hepatotoxicity in normal zebrafish， but under osteoporotic conditions， XLGB not only exerts significant anti-osteoporosis activity but also alleviates hepatotoxicity significantly， which provides a reference for the safe clinical use of XLGB and real evidence for the theories of traditional Chinese medicine of attacking poison with poison and of treating disease with corresponding drugs without damage to the body.

The diseases and pathological manifestations associated with chongmai (thoroughfare vessel) are the representative in the practical applications of chongmai theory. Elucidating this theory serves as a prerequisite of acupuncture and moxibustion therapy. Based on literature analysis, the diseases and clinical manifestations of chongmai recorded in the time of Huangdi Neijing (The Yellow Emperor's Inner Classic) were analyzed so as to reinterpret the diagnostic process, pathological characteristics, and clinical manifestations of disorders, and evaluate the value of chongmai theory. Chongmai diseases were identified from the palpation initially, known as the "palpation on abdominal pulse". The "qi reversion" of chongmai represents a typical clinical manifestation of chongmai diseases, such as ji (abdominal mass), jia (abdominal hematoma), and shan (hernia), occurring in different sites of the abdomen and in different pathological stages. A part of distribution of chongmai is considered in clinical manifestation, diagnosis and treatment of acupuncture and moxibustion. To emphasize the significance of chongmai in modern acupuncture-moxibustion theory and practice, the diagnostic and therapeutic patterns of the related disorders should be considered in clinical practice. The characteristics of chongmai are reflected in three aspects: qi, blood and abdomen, which are determined by both its inherent properties and the clinical manifestations of related diseases.
Humans ; Acupuncture Therapy ; Moxibustion ; History, Ancient ; Meridians ; Medicine, Chinese Traditional

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

By analyzing the understandings of water points (acupoints connected with the kidney) and its association with water (kidney), zangfu organs and meridian-collateral recorded in Suwen: Shuire Xue Lun (Discussion on Water and Heat Diseases in Plain Question), it is found that the recognition on the water points is different from that on water diseases in Huangdi Neijing (the Yellow Emperor 's Inner Classic). The recognition on the water points focuses on the core theory, "rooted at the kidney", to explain the water diseases. Besides, in association with the study on the connotation of "luo" in Huangdi Neijing, it is discovered that "yinluo" discussed in water points is actually the misunderstanding of "zang zhi yinluo" that means "the connection by the kidney". It is shown that the discussion of water points refer to the elaboration of zangfu organs and 57 acupoints connected with water (the kidney), rather than the theory of collaterals. The characteristics of these 57 acupoints involved and the related needling techniques provide a new approach to the treatment of zangfu diseases.
Acupuncture Points ; Humans ; Meridians ; China ; History, Ancient ; Medicine in Literature ; Medicine, Chinese Traditional/history* ; Acupuncture Therapy/history*

OBJECTIVES: Pyroptosis plays a critical role in tubulointerstitial lesions of diabetic kidney disease (DKD). Annexin A2 (ANXA2) is involved in cell proliferation, apoptosis, and adhesion and may be closely related to DKD, but its specific mechanism remains unclear. This study aims to investigate the role and molecular mechanism of ANXA2 in high glucose-induced pyroptosis of renal tubular epithelial cells, providing new targets for DKD prevention and treatment. METHODS: Human renal tubular epithelial HK-2 cells were divided into a normal glucose group (5.5 mmol/L), a high glucose group (30.0 mmol/L), and a osmotic control group (24.5 mmol/L mannitol+5.5 mmol/L glucose). ANXA2 expression was modulated by overexpression of plasmids and small interfering RNA (siRNA). Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, apoptosis by flow cytometry, and ANXA2, p50, and p65 subcellular localization by immunofluorescence. Western blotting was employed to detect α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type IV (Col-IV). Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting were used to analyze nuclear factor-κB (NF-κB) subunits p50/p65 and the pyroptosis pathway factors NLR family Pyrin domain containing 3 (NLRP3), caspase-1, inferleukin (IL)-1β, and IL-18. Protein interactions between ANXA2 and p50/p65 were examined by co-immunoprecipitation, while chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to examine NF-κB binding to the ANXA2 promoter. RESULTS: High glucose upregulated ANXA2 expression and promoted its nuclear translocation (P<0.01). High glucose reduced cell proliferation, increased apoptosis, and elevated α-SMA, FN, and Col-IV expression (all P<0.05); ANXA2 overexpression aggravated these effects (all P<0.05), while ANXA2 knockdown reversed them (all P<0.05). High glucose activated NF-κB and increased NLRP3, caspase-1, L-1β, and IL-18 mRNA and protein expression (all P<0.05); ANXA2 overexpression further enhanced this, whereas knockdown suppressed NF-κB activation and downstream factors (all P<0.05). Co-immunoprecipitation confirmed ANXA2 directly binds the NF-κB subunit p65. ChIP assays revealed p65 binds specifically to ANXA2 promoter regions (ChIP-2, ChIP-4, and ChIP-6), and luciferase activity in corresponding mutant constructs (M2, M4, and M6) was significantly increased versus controls (all P<0.05), confirming positive transcriptional regulation of ANXA2 by p65. CONCLUSIONS ANXA2 and NF-κB form a positive feedback loop that sustains NLRP3 inflammasome activation, promotes pyroptosis pathway activation, and aggravates high glucose-induced renal tubular epithelial cell injury. Targeting ANXA2 or blocking its interaction with p65 may be a novel strategy to slow DKD progression.
Humans ; Pyroptosis/drug effects* ; Annexin A2/physiology* ; Epithelial Cells/cytology* ; Kidney Tubules/cytology* ; Glucose/pharmacology* ; Diabetic Nephropathies/metabolism* ; NF-kappa B/metabolism* ; Cell Line ; Cell Proliferation ; Transcription Factor RelA/metabolism* ; Feedback, Physiological

Under the background of high-intensity fattening,probiotics have gradually become wide-ly used feed additives.It can inhibit the proliferation of pathogenic bacteria,maintain the microeco-logical balance in the digestive tract,and improve the host immune function.In order to screen lac-tic acid bacteria strains with potential probiotic effects,23 acid-producing strains were isolated from rumen fluid of healthy Duolang sheep by CaCO3-MRS solid medium.Safe strains were re-screened through primary screening and hemolysis tests.Acid tolerance tests and bile salt tests were used to screen the strains that were relatively adapted to the rumen environment.The survival rate of the strain M2 was 93.80％under pH3.0 and 59.72％under bile salt concentration of 0.30％and the survival rate is higher than other strains under high temperature conditions.Subsequently,morphological observation,molecular biological identification,testing of pathogen antagonism,antibiotic tolerance analysis,growth characteristics detection and other methods were used to fur-ther explore the characteristics of the strain.The results showed that the strain to be tested was Gram-positive bacillus.After 16S rRNA gene sequence comparison,the strain was identified as Lactobac illus salivus,which could be used as a candidate strain to develop probiotics.The research results laid a foundation for its application in Duolang sheep breeding.

Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.

Objective:To compare the quality of Astragali Radix at different harvest time; To revise the content determination indexes of Astragali Radix in Chinese Pharmacopoeia. Methods:An Agilent Eclipse XDB-C18 column (4.6 mm × 150 mm, 5 μm) was used for the determination of saponins with acetonitrile-water solution as mobile phase in a gradient mode. The drift tube temperature of ELSD was 60 ℃; the pressure was 30 psi; the gain was 800 ℃; the flow rate was 1.0 ml/min; the column temperature was 30 ℃; the injection volume was 20 μl; the acetonitrile-0.2% formic acid solution was used as mobile phase for the determination of flavonoids in a gradient mode; the flow rate was 1.0 ml/min; the detection wavelength was 260 nm; the column temperature was 30 ℃; the 10 μl was injected. The limited range as an indicator for determining Astragali Radix content was determined by investigating the extraction method and extraction time of Astragaloside Ⅰ and detecting the content of Astragaloside Ⅰ in 12 batches of Astragali Radix from different origins. The moisture, total ash, and water-soluble extracts in Astragali Radix were determined according to the drying method, total ash determination method, and cold soaking method in the four parts of Chinese Pharmacopoeia (2020 edition), respectively. Results:The content of total saponins in Astragali Radix harvested in spring and autumn in different origins was not significantly different, but the content of total flavonoids was significantly different. Except for H11, the content of Astragaloside Ⅰ in the other batches of Astragali Radix was ≥ 0.05%, so the content limit of Astragaloside Ⅰ was proposed to be≥0.05%. The results of moisture, total ash and water-soluble extracts in the 12 batches of Astragali Radix all meet the requirements in the Chinese Pharmacopoeia. Conclusions:Astragali Radix harvested in autumn is with higher content of active components and better quality. At the same time, this study can provide a reference that the new version of Chinese Pharmacopoeia can revise the Astragaloside Ⅳ in the content determination index of Astragali Radix to Astragaloside Ⅰ .

Objective:To evaluate the effect of continuous positive airway pressure (CPAP) ventilation during induction of anesthesia on perioperative atelectasis and oxygenation in elderly patients.Methods:Forty-six elderly patients of either sex, aged 65-80 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, undergoing elective cerebrovascular intervention surgery under general anesthesia, were divided into 2 groups ( n=23 each) according to the random number table method: control group (group C) and CPAP ventilation group (group CPAP). During induction of anesthesia, CPAP was set at 5 cmH 2O during spontaneous breathing, and PEEP was set at 5 cmH 2O when spontaneous breathing disappeared, and the ventilation mode was changed to pressure-controlled ventilation (PCV) mode in group CPAP. CPAP was not set, and PEEP was set at 0 cmH 2O for PCV when spontaneous breathing disappeared in group C. During anesthesia maintenance, PCV-volume guaranteed mode was used in both groups, and PEEP was set at 5 cmH 2O. Whole lung CT scanning was performed immediately after radial artery catheterization (T 0), at 1 min after endotracheal intubation (T 1), and before tracheal extubation (T 2) at the end of operation to calculate the percentage of atelectasis area at 1 cm above the right diaphragm. At T 0, T 1, T 2 and 30 min after entering postanesthesia care unit (T 3), blood samples from the radial artery were taken to record PaO 2 and PaCO 2 and calculate the oxygenation index (OI). Results:Compared with the baseline at T 0, the percentage of atelectasis area was significantly increased at T 1 and T 2 in two groups ( P<0.05); PaO 2 was significantly increased at T 1 and T 2 and decreased to T 0 level at T 3, OI was decreased at T 1 and T 2 and increased to T 0 level at T 3 in two groups ( P<0.05). Compared with group C, the percentage of atelectasis area was significantly decreased and PaO 2 and OI were increased at T 1 and T 2 in group CPAP ( P<0.05). There was no significant difference in PaCO 2 at each time point between the two groups ( P>0.05). Conclusions:CPAP ventilation during induction of anesthesia can reduce the development of perioperative atelectasis and improve the oxygenation in elderly patients.

Objective:To evaluate the effect of continuous positive airway pressure(CPAP) ventilation strategy during induction of general anesthesia on atelectasis after induction in obese patients.Methods:A total of 86 patients, aged 30-60 yr, with body mass index of 28-35 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱor Ⅲ, scheduled for elective cerebrovascular intervention under general anesthesia, were divided into 2 groups ( n=43 each) using a random number table method: CPAP group (group C) and routine group (group R). Group C received CPAP 5 cmH 2O-assisted ventilation after preoxygenation for spontaneous breathing and disappearance of spontaneous breathing. Chest CT scan and arterial blood gas analysis were performed after entering the operating room (T 1) and 5 min after endotracheal intubation (T 2) to calculate the percentage of atelectasis area and to record PaO 2. Dynamic lung compliance and plateau pressure were recorded at T 2. Mean minute ventilation under controlled breathing, P ETCO 2, and use of vasoactive drugs during induction were recorded. The occurrence of reflux and aspiration during mask ventilation was recorded. The development of pulmonary complications within 3 days after operation was recorded. Results:Compared with group R, the percentage of atelectasis area at T 2 was significantly decreased, PaO 2, dynamic lung compliance and plateau pressure were increased ( P<0.05), and no significant change was found in mean minute ventilation, P ETCO 2, requirement for vasoactive drugs and incidence of pulmonary complications in group C ( P>0.05). No reflux or aspiration was observed during mask ventilation. Conclusions:CPAP (5 cmH 2O) strategy during anesthesia induction can reduce the degree of atelectasis after induction in obese patients.