ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

ObjectiveTo investigate whether Danggui Shaoyaosan （DSS） inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK）/nuclear factor kappa-B （NF-κB） signaling pathway， thereby delaying the progression of diabetic kidney disease （DKD） and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group， and forty 8-week-old db/db mice were randomly divided into the model group， DSS low-dose group （8.39 g·kg^-1）， DSS medium-dose group （16.77 g·kg^-1）， DSS high-dose group （33.54 g·kg^-1）， and irbesartan group （0.025 g·kg^-1）， with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration， changes in body weight， fasting blood glucose （FBG）， and 24 hour urinary protein （24 h UTP） were observed. After 12 consecutive weeks of administration， hematoxylin-eosin （HE） staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species （ROS） in renal tissue were detected using the dihydroethidium （DHE） method. The expression levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissue were determined. Serum interleukin-1β （IL-1β） and interleukin-6 （IL-6） levels were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of RhoA， ROCK1， and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of fibronectin （FN）， Collagen Ⅳ（Col Ⅳ）， transforming growth factor-β₁ （TGF-β₁）， RhoA， ROCK， and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed significantly increased body weight， FBG， and 24 h UTP levels （P<0.01）， elevated serum IL-1β and IL-6 levels， enlarged glomerular volume， diffuse mesangial expansion， increased mesangial matrix， and marked collagen fiber proliferation in renal tissues. SOD activity was decreased， while MDA， ROS， RhoA， ROCK1， and NF-κB p65 mRNA expression levels were increased （P<0.01）， and the protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 were also elevated （P<0.01）. Compared with the model group， the DSS low-， medium-， and high-dose groups and the irbesartan group showed reductions in body weight， FBG， and 24 h UTP， decreased serum IL-1β and IL-6 levels， varying degrees of improvement in renal histopathology， increased SOD activity， decreased MDA levels， reduced ROS expression， and significantly downregulated RhoA， ROCK1， and NF-κB p65 mRNA expression （P<0.05， P<0.01）， as well as reduced protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 （P<0.05， P<0.01）. ConclusionDSS can alleviate oxidative stress and inflammation， reduce extracellular matrix deposition， and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway， thereby exerting a therapeutic effect on DKD.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To evaluate the effect of endoscopic laryngeal mask on perioperative airway management and postoperative recovery in patients undergoing gastric endoscopic submucosal dissection(ESD).Methods Ninety patients,aged 18-64 years,BMI 18-25 kg/m2,ASA physical statusⅠorⅡ,who underwent elective gastric ESD were randomly divided into two groups:the endoscopic laryngeal mask group(group E)and the endotracheal tube group(group C),45 patients in each group.After induction of general anesthesia,group E received endoscopic laryngeal mask airway ventilation,and the endoscope was inserted through the endoscopic channel of the laryngeal mask,group C received tracheal intubation,and the endoscopy was inserted through the mouth.The successful time and one-time success rate of intubation,and the insertion time and withdrawal rate of endoscopy were recorded.The operative time,extubation time and PACU residence time were recorded.HR,MAP were recorded when the patient entered the room(T0),at the time of intubating(T1),inserting gastroscopy(T2),exiting gastroscopy(T3),extubation(T4),and leaving PACU(T5).The average airway pressure and peak airway pressure at T1-T3 were recorded.The airway sealing pressure and endoscopic view grading system(EVGS)grading of group E were recorded before and after changing the position,and at the end of surgery.The adverse reactions and the satisfaction of anesthesiologists and gastroenterologists were recorded.Results Compared with T0,HR and MAP were significantly increased at T1 and T4 between the two groups(P＜0.05).Compared with group C,the suc-cessful time of intubation,the extubation time,and PACU residence time were significantly shortened,HR and MAP were significantly decreased at T1 and T4,the incidence of choking cough during extubation,post-operative pharyngeal pain,and hoarseness were significantly decreased(P＜0.05).There were no signifi-cant differences in the one-time success rate of intubation,the insertion time and withdrawal rate of endosco-py between the two groups.Endoscopic laryngeal mask showed good sealing and alignment in group E.Conclusion Endoscopic laryngeal mask could shorten the success time of establishment of artificial airway in patients with gastric ESD,without interfering with digestive endoscopy operations,shorten extubation time and PACU retention time,maintain intraoperative hemodynamic stability,and reduce adverse reactions.

Craniocerebral injury with seawater immersion is a special kind of compound injury, with low temperature, high permeability, high alkali, high salt content, and bacterial infection being the main causes. The injury is also characterized with complex damage mechanisms, difficulty to treat, and poor prognosis. At present, the damage mechanisms of craniocerebral injury with seawater immersion are mainly studied by establishing the experimental animal models at the levels of tissue, cell, organelle, molecule, etc. However, the craniocerebral injury with seawater immersion is more complex than the simple onshore craniocerebral injury, therefore, a stable disease model is not easy to construct. Most researches on the specific injury mechanisms are relatively single and one-sided, with many different views in existence, and the damage mechanisms of craniocerebral injury with seawater immersion have hitherto not been clear. The authors reviewed the research progress in the damage mechanisms of craniocerebral injury with seawater immersion, in order to promote the in-depth study of the mechanism of craniocerebral injury with seawater immersion and provide reference for its clinical treatment.

Humans ; DNA, Mitochondrial ; Cross-Sectional Studies ; East Asian People ; DNA Methylation ; Hypertension/epidemiology* ; China/epidemiology*

Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ² test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.

Objective:To evaluate the effect of electroacupuncture on the heme oxygenase-1 (HO-1)/PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway during acute kidney injury in endotoxemic rats.Methods:Twenty-four SPF healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 4 groups ( n=6 each) by a random number table method: control group(group C), endotoxemia group(group E), acupoint electroacupuncture+ endotoxemia group(group EE), and non-acupoint electroacupuncture+ endotoxemia group(group NE). The endotoxemia model was developed by intraperitoneal injection of lipopolysaccharide 10 mg/kg. The equal volume of normal salinewas injected in group C. LPS 10 mg/kg was intraperitoneally injected in group E. In group EE, 30-min electroacupuncture was performed at bilateral Zusanli and Shenshu acupoints using disperse-dense waves with a frequency of 2/15 Hz to induce slight muscle tremor once a day starting from 5 days before developing the model, and the needle was retained until 6 h after injection. Electroacupuncture was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenshu in group NE. The rats were anesthetized at 6 h after lipopolysaccharide injection, and blood samples from the femoral vein were obtained for determination of the serum creatinine (Cr) and urea nitrogen (BUN) concentrations(with a biochemical analyzer) and concentrations of neutrophil gelatinase-associated lipid transport protein (NGAL), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and kidney injury molecule-1(KIM-1) in serum (by enzyme-linked immunosorbent assay). Then the rats were sacrificed and kidney tissues were taken for determination of histological score of kidneys (HSK, using HE staining) and expression of HO-1, PINK1, Parkin, mitochondrial fusion protein 2(Mfn2), optic atrophy protein 1(OPA1) and mitochondrial dynamic-related protein 1 (Drp1) (by Western blot). Results:Compared with group C, serum concentrations of Cr, BUN, KIM-1, NGAL, IL-6 and TNF-α and HSK score of renal tissues were significantly increased, the expression of HO-1, PINK1, Parkin and Drp1 was up-regulated, and the expression of Mfn2 and OPA1 was down-regulated in E, EE and NE groups ( P<0.05). Compared with group E, serum concentrations of Cr, BUN, KIM-1, NGAL, IL-6 and TNF-α and HSK score of renal tissues were significantly decreased, and the expression of HO-1, PINK1, Parkin, Mfn2 and OPA1 was up-regulated, and Drp1 expression was down-regulated in group EE( P<0.05), and no significant change was found in the parameters mentioned above in group NE ( P>0.05). Conclusions:The mechanism by which electroacupuncture alleviates acute kidney injury is associated with activation of HO-1/PINK1/Parkin signaling pathway in endotoxemic rats.