Effects of Mild Moxibustion on Proteins Expression of BDNF/TrkB Signaling Pathway in Hypothalamus of Primary Dysmenorrhea Rats with Cold and Dampness Stagnation Syndrome / 中国中医药信息杂志

Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.

The relationship between blood cell-related inflammatory markers and diabetic retinopathy: a study from Beichen Eye Study / 中华眼底病杂志

Objective:To observe the correlation between blood cell-related inflammatory markers and diabetic retinopathy (DR).Methods:A cross-sectional study. From June 2020 to February 2022, the phase Ⅰ data of Beichen Eye Study in Tianjin Medical University Eye Hospital were included in the study. The research contents included questionnaires, routine systemic and ocular examinations, and laboratory blood cell-related indicators including mean platelet volume (MPV), platelet distribution width (PDW), neutrophils, and lymphocytes were performed. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were calculated. The diagnosis and classification of DR referred to the international clinical classification standard of DR. Monocular or binocular DR was defined as DR patients. Participants were categorized into different groups based on whether they had diabetes and whether they had DR. The groups included the no-diabetes group, the diabetes without DR group, and the DR group. The Kruskal-Wallis H test was used for the comparison of quantitative data among multiple groups. Wilcoxon test was used for comparison between the two groups. The χ2 test was used to compare the categorical variables between groups. The variables was adjusted step by step, an unadjusted univariate model was built and the different parameters of the model Ⅰ, Ⅱ, Ⅲ were adjusted. The correlation between MPV, PDW, NLR, PLR, and DR in different models was analyzed by logistic regression. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different NLR models for DR. Results:A total of 3 328 subjects were recruited. Among them, 1 121 (33.68 %, 1 121/3 328) were males and 2 207 (66.32 %, 2 207/3 328) were females. The median age of the included participants was 61.84 (6.05) years. The no-diabetes group, the diabetes without DR group, and the DR group were 2 679, 476, and 173, respectively. There was no significant difference in MPV and PLR among the three groups ( H=5.98, 1.94; P=0.051, 0.379). However, compared with no-diabetes group and the diabetes without DR group, PDW and NLR in the DR group showed an upward trend. In model Ⅲ with completely adjusted related factors, NLR was an independent risk factor for DR in no-diabetes group and DR group [odds ratio ( OR)=1.440, 95% confidence interval ( CI) 1.087-1.920, P=0.041], diabetes without DR group and DR group [ OR=1.990, 95% CI 1.440-2.749, P<0.001]. The results of ROC curve analysis showed that the diagnostic efficiency of NLR model Ⅲ was the highest, the area under the curve was 0.751 (95% CI 0.706-0.796, P<0.001), the optimal cutoff value was 0.390, and the sensitivity and specificity were 74.3% and 64.8%, respectively. Conclusions:The NLR of the DR group is significantly higher than that of the no-diabetes group and diabetes without DR group. NLR is an independent risk factor for DR.

Implication of Qidi Tangshen Prescription （QDTS） on Podocyte Pyroptosis in Diabetes Nephropathy by Regulating MAPK14/RELA/Caspase-8 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg-1）， valsartan capsule group （10.29 mg·kg-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L-1 glucose）， high glucose group （35 mmol·L-1 glucose）， DMSO group （35 mmol·L-1 glucose+200 mg·L-1 DMSO）， and QDTS group （35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.

Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum （ER） stress and reducing urinary protein in the rat model of diabetic nephropathy （DN）. MethodSeventy-five SD rats were randomized into normal， model， low-， medium-， and high-dose （4.37， 8.73， 17.46 g·kg-1， respectively） modified Shengjiangsan， and irbesartan （0.014 g·kg-1） groups， with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage， once a day， for 8 consecutive weeks. After the last administration， the levels of glucose （GLU） in the blood， 24-hour urinary protein （24 h-UTP）， and superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in the renal tissue were measured. Hematoxylin-eosin staining， periodic acid-Schiff staining， and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin， podocin， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， and activating transcription factor 4 （ATF4） in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 （Sirt1）， phosphorylated （p）-protein kinase RNA-like endoplasmic reticulum kinase （PERK）， and p-eukaryotic translation initiation factor 2 alpha （eIF2α） in rat kidneys. ResultCompared with the normal group， the modeling caused pathological damage to the kidneys， elevated the levels of GLU and 24 h-UTP （P<0.05）， up-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and down-regulated the protein level of Sirt1 （P<0.05） in rat kidneys. Compared with the model group， modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels （P<0.05）， alleviated the pathological damage in the renal tissue， down-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and up-regulated the protein level of Sirt1 （P<0.05）. ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue， thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.

Qidi Tangshen Prescription （QDTS） Regulate Akt1/HIF-1α/Bcl-xl Signaling Pathway to Improve Podocyte Autophagy in Diabetic Nephropathy / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg-1）， and losartan capsules （10.29 mg·kg-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L-1）， high glucose （35 mmol·L-1）， DMSO （35 mmol·L-1 glucose+200 mg·L-1 DMSO）， and QDTS （35 mmol·L-1 glucose+200 mg·L-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.

Application of DSI Studio Software Combined with DTI in Motor Function Evaluation of Postoperative Brain Functional Area Tumor / 医学研究杂志

Objective To study the value of DSI Studio combined with diffusion tensor imaging(DTI)in evaluating the prognosis of postoperative motor function in patients with brain functional area tumors.Methods From January 2018 to August 2022,41 patients with brain functional area tumors who underwent surgical treatment and were pathologically diagnosed in our hospital were included in the study.All patients completed 3.0 T MRI routine sequence and DTI examination.DTI parameters of the corticospinal tract(CST)projection area of posterior limb of the internal capsule on the affected side and the healthy side were measured respectively,and the correlation with MRC muscle strength score and the CST grade was analyzed.Results The FA value of the affected side was significantly lower than that of the healthy side(P＜0.001),and the ADC value of the affected side was significantly higher than that of the healthy side(P＜0.001).The FA value of the affected side and the lateral rFA value were negatively correlated with the CST grade(P＜0.01).ADC value and rADC value were positively correlated with CST grade(P＜0.01).The FA value of the affected side and the partial rFA value were positively correlated with the degree of muscle strength score before and after surgery(P＜0.01).ADC value and rADC value were negatively corre-lated with CST grade(P＜0.01).Preoperative CST grading was negatively correlated with contralateral muscle strength.The area under the ROC curve of FA value,rFA value,ADC value,rADC value,and CST grade were 0.820(P＜0.01),0.796(P＜0.01),0.698(P＜0.05),0.638(P＞0.05)and 0.708(P＜0.05),respectively.Conclusion DTI parameters,muscle strength score and CST grade have certain value in the evaluation of postoperative motor function prognosis in patients with brain functional tumors.

Physicochemical Processes of Biofilm Formation on The Surface of Structures in Water / 生物化学与生物物理进展

Microorganisms can form biofilms, complex, heterogeneous, multicellular communities that adhere to surfaces. Biofilm formation on the surface of structures in water will accelerate structures’ corrosion, seriously affect their service efficiency and life, and significantly impact the growth of animals, plants, and human life. Hence, clarifying the mechanism of biofilm formation contributes to developing new strategies to control biofilm formation on surface and then reduce infections, biofouling, and contaminations. Biofilm-targeting strategies include the regulation of established biofilms or the modulation of single-cell attachment. In most studies, physicochemical mechanism is frequently applied to explain the initial bacterial adhesion phenomena but rarely to explain other stages of biofilm formation. This review presents a five-step comprehensive description of the physicochemical process from film formation to biofilm maturation: (1) period of film formation; (2) period of bacterial adhesion; (3) period of extracellular-polymeric-substances (EPSs) membrane formation; (4) period of regulating biofilm by quorum sensing (QS); (5) period of biofilm maturation. We first clarify how the film formed by compound molecules affects the surface’s physicochemical properties and initial adhesion, summarizing many factors that affect bacterial adhesion. We then review the types of EPSs and signal molecules secreted by bacteria after irreversible adhesion, as well as their role and QS mechanism in biofilm maturation. Finally, we discuss how bacteria or microcolonies separate from the mature biofilm by physicochemical action and summarize the morphology and adhesion characterization methods after the biofilm matures. This review redefines the role of physicochemical in the whole process of biofilm formation and provides a theoretical basis for the prevention, removal, and utilization of biofilm and other related research fields.

Effect of Dahuang Xiezhuo Prescription on Inflammation and SOCS3/TLR4 Pathway in Rats with Chronic Renal Failure / 中国实验方剂学杂志

ObjectiveTo observe the intervention effect of Dahuang Xiezhuo prescription （DHXZ） on inflammation and suppressor of cytokine signaling 3 （SOCS3）/Toll-like receptor 4 （TLR4） pathway in rats with chronic renal failure （CRF）， and to explore its molecular mechanism in alleviating renal inflammatory response. MethodThe 90 male SD rats， 15 were randomly selected as sham group， and the remaining 75 were used as modeling group to replicate CRF rat model by 5/6 nephrectomy. After successful modeling， the rats were randomly divided into model group， DHXZ low-， medium-， high-dose groups （6.825， 13.65， 27.3 g·kg-1） and Niaoduqing Granules group （2.6 g·kg-1）. The drug intervention groups received corresponding drugs by gavage for 8 consecutive weeks. After administration， hematoxylin-eosin （HE） staining and Masson staining were used to observe the morphological changes of rat renal tissue， and blood creatinine （SCr）， blood urea nitrogen （BUN） and blood uric acid （UA） were tested. Enzyme-linked immunosorbent assay （ELISA） was performed to detect the serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and C-reactive protein （CRP）. The mRNA expressions of SOCS3 and TLR4 in renal tissue were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of SOCS3， TLR4， nuclear transcription factor （NF-κB） and myeloid differentiation factor （MyD88） were detected by Western blot. Immunohistochemistry was used to determine the protein expressions of NF-κB， MyD88， NOD-like receptor protein 3 （NLRP3） and melanoma deficiency factor 2 （AIM2）. ResultCompared with the sham group， the model group had a significant inflammatory response in renal tissue， and an increase in blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. The protein and mRNA expressions of SOCS3 in renal tissue of rats in the model group were lower while the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 were higher than those in the sham group （P<0.05）. Compared with the model group， DHXZ and Niaoduqing granules groups presented markedly reduced inflammatory response in renal tissue and decreased blood SCr， BUN， UTP， IL-6， TNF-α and CRP （P<0.05）. Additionally， DHXZ and Niaoduqing granules up-regulated the protein and mRNA expressions of SOCS3 in renal tissue while down-regulated the protein expressions of TLR4， NF-κB， MyD88， NLRP3 and AIM2 and the mRNA expression of TLR4 （P<0.05）. ConclusionDHXZ can reduce the release and expression of inflammatory factors， inhibit the inflammatory response and improve renal function， and the mechanism may be related to the regulation of SOCS3/TLR4 signaling pathway.

Mechanism of Salvianolate in Inducing Autophagy in Podocytes of Rats with Membranous Nephropathy via AMPK/SIRT1/PGC-1α Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of salvianolate on the protein expressions of adenosine monophosphate （AMP）-activated protein kinase （AMPK）， silent information regulator 1 （SIRT1） and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α）， autophagy and apoptosis in kidney tissue of rats with membranous nephropathy （MN）， and to explore its possible molecular mechanism against MN. MethodEighty male SD rats were randomly divided into normal group， model group， benazepril hydrochloride group （10 mg·kg-1）， and salvianolate low-， medium-， and high-dose groups （16.7， 33.3 and 66.7 mg·kg-1）. The rats were modeled by injection of cationized bovine serum albumin （C-BSA） into the tail vein. After successful modeling， rats in the administration groups were given corresponding doses of drugs for 4 consecutive weeks， and then 24-hour urine， serum and kidney tissue were collected for the detection of 24-hour urinary protein （UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， C reactive protein （CRP）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， and malondialdehyde （MDA）. The pathological changes of kidneys were observed by light microscope， electron microscope and immunofluorescence. Western blot was used to detect the protein expressions of phospho-AMPK （p-AMPK）， AMPK， phospho-SIRT1 （p-SIRT1）， SIRT1 and PGC-1α in rat kidney tissue. The protein expressions of autophagy-specific gene （Beclin-1）， microtubule-associated protein 1 light chain 3 （LC3） Ⅱ， ubiquitin-binding protein （p62）， B cell lymphoma （Bcl-2）， Bcl-2-associated X （Bax）， and cysteine aspartic protease-7 （Caspase-7） in rat kidney tissue were determined by immunohistochemistry （IHC）. ResultCompared with the conditions in the normal group， the levels of UTP， IL-6， TNF-α， CRP and MDA in the model group were increased （P<0.05） while the levels of SOD and GSH-Px were decreased （P<0.05）， and there was no difference in BUN and SCr. Compared with the model group， the administration groups had lowered UTP， IL-6， TNF-α， CRP and MDA （P<0.05） while elevated SOD and GSH-Px （P<0.05）. It could be seen from hematoxylin and eosin （HE） staining， Masson staining， immunofluorescence and electron microscopy that the pathological damage of rat kidney tissue in the model group was significant， but after treatment with benazepril hydrochloride and salvianolate， the pathological damage of kidney cells was gradually improved. The expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in rat kidney in the model group were lower than those in the normal group （P<0.05） while the expressions of Bax， Caspase-7 and p62 were higher （P<0.05）. Compared with the model group， benazepril hydrochloride group and salvianolate groups had an up-regulation in the expressions of p-AMPK/AMPK， p-SIRT1/SIRT1， PGC-1α， Bcl-2， Beclin-1 and LC3Ⅱ in the kidney （P<0.05） while a down-regulation in the expressions of Bax， Caspase-7 and p62 （P<0.05）. ConclusionThe protective effect of salvianolate on the kidneys of MN rats may be related to the activation of AMPK/SIRT1/PGC-1α signaling pathway， the up-regulation of autophagy and the reduction of apoptosis.

Percutaneous ablation of liver metastases from colorectal cancer: a comparison between the outcomes of ultrasound guidance and CT guidance using propensity score matching

Purpose@#The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). @*Methods@#This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients’ initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)–free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. @*Results@#PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). @*Conclusion@#For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.

Clinical evaluation of platelet-rich plasma in the treatment of early and middle stage knee osteoarthritis under 3.0T MRI T2 mapping sequence / 中华外科杂志

Objective: To quantitatively evaluate the clinical effect of platelet-rich plasma(PRP) intra-articular injection for early and middle stage knee osteoarthritis(KOA) treatment by 3.0T MRI T2 mapping sequence. Methods: Clinical data of 26 patients with early or middle stage KOA who received treatment from April to December 2021 at Department of Orthopaedic Surgery,the Second Affiliated Hospital,Zhengzhou University were retrospectively analyzed. In total, 8 patients were male and 18 were female,with age of (66.4±12.0)years(range:51 to 94 years). Four patients were bilateral KOA and 22 patients were unilateral KOA.All patients received PRP intra-articular injection. Patients underwent 3.0T MRI T2 mapping sequence scanning pre-treatment,3-month-after and 6-month-after treatment respectively. Those were used to measure and compare T2 values of medial and lateral femoral articular surface and patellofemoral articular surface. Visual analogue scale(VAS) and Western Ontario and McMaster Osteoarthritis Index (WOMAC) score were recorded and evaluated. The results were analyzed using repeated measure ANOVA followed by Bonferroni multiple comparison test.The correlation between WOMAC scores and T2 values at pre-treatment and 6 months post-treatment was analyzed using Pearson correlation test. Results: After treatment, the patients' International Cartilage Regeneration＆Joint Preservation Society(ICRS) classification were partly improved(one case improved from grade Ⅲ to grade Ⅱ, one case improved from grade Ⅱ to grade Ⅰ),and all patients generally improved after treatment in clinical symptoms. Compared with pre-treatment,VAS and WOMAC scores of grade Ⅰ,Ⅱ,and Ⅲ of 6-month after treatment were declined significantly(all P<0.05).The T2 values of articular cartilage declined to varying degrees(the decrease in T2 values was about 2.06 ms in grade Ⅰ, 2.66 ms in grade Ⅱ, and 3.72 ms in grade Ⅲ).Three-month (VAS:4.8±1.3,WOMAC:21.5±4.0) and 6-month (VAS:4.2±1.4,WOMAC:17.2±2.9) after treatment, the VAS and WOMAC score were significantly higher than those before treatment (VAS:6.0±1.2, WOMAC:29.0±2.3) (F=48.846, F=346.746;both P<0.01). Multiple comparisons showed a statistically significant difference between pre-treatment and post-treatment VAS (P<0.01) and it also was significantly different between 3-month and 6-month post-treatment (P<0.01).At 3- and 6-month after treatment,WOMAC scores were significantly different from before treatment.And it also was significantly different between 3-month and 6-month post-treatment (P<0.01).There was a statistically significant improvement in T2 values of patellofemoral articular surface, medial and lateral femoral articular surface at pre-treatment((44.64±4.02)ms,(44.17±3.64)ms and(43.53±3.91)ms) and 3-month ((43.19±3.91)ms,(43.24±3.34)ms and (42.47±3.80)ms), 6-month ((41.49±3.64)ms,(41.83±3.15)ms and (41.10±3.42)ms) after treatment(F=148.845,F=73.657,F=86.268;all P<0.01).The results of the multiple comparisons showed a statistically significant difference in the T2 values of medial and lateral femoral articular surface and patellofemoral articular surface at each time point(all P<0.01).The Pearson correlation analysis suggested that the WOMAC score at pre-treatment was positively correlated with the medial condyle (r=0.856,P<0.01) and the patellofemoral joint surface T2 values (r=0.840,P<0.01);The WOMAC score at 6-month post-treatment was positively correlated with the medial condyle (r=0.731,P<0.01) and the patellofemoral joint surface T2 values (r=0.691,P<0.01). Conclusions: In the treatment of early and mid-stage KOA,MRI T2 mapping sequences are able to indicate the integrity of cartilage morphology and quantitatively evaluate cartilage repair. PRP has a good therapeutic effect on cartilage repair and reconstruction.

Clinical characteristics and rehabilitation of dysphagia after brainstem stroke / 中国康复理论与实践

ObjectiveTo investigate the clinical characteristics of dysphagia after brainstem stroke, and rehabilitation effect and influencial factors for it. MethodsA retrospectively analysis was conducted in patients who were diagnosed as dysphagia after brainstem stroke in the Beijing Bo'ai Hospital from April, 2018 to December, 2021. The following data were collected: the general information (gender, age, course of disease, and time of treatment), the result of videofluoroscopic swallowing study (VFSS), the Dysphagia Severity Scale (DSS) score before and after treatment, the scores of Fugl-Meyer Assessment (FMA), FMA-Balance (FMA-B), National Institutes of Health Stroke Scale (NIHSS) and Barthel index (BI), Mini-Mental State Examination (MMSE), and whether oral feeding. Based on the result of VFSS, all patients were divided into non-cricopharyngeal achalasia group (control group) and cricopharyngeal achalasia group (observation group). ResultsA total of 60 patients were collected, with 29 in the control group and 31 in the observation group. The scores of FMA, FMA-B, BI and MMSE were higher (|t| > 3.281, P < 0.01), and the NIHSS score was lower (t = 4.390, P < 0.001) in the observation group than in the control group. Before treatment, the score of DSS was significantly lower in the observation group than in the control group (t = 5.785, P < 0.001); after treatment, the scores improved in both groups (|t| > 5.387, P < 0.001), and no significant difference was found between two groups (t = 1.675, P = 0.099); however, the d-value was more in the observation group than in the control group (t = -2.729, P = 0.008). There was no significant difference in the rate of oral feeding (χ² = 2.742, P = 0.098). In the control group, there were differences in the scores of NIHSS, FMA-B, BI and DSS between patients with oral feeding and those with nasal feeding (|t| > 2.429, P < 0.05); however, no significant difference was found in all factors in the observation group (P > 0.05). The DSS score was the influence factor of oral feeding in the control group (OR = 3.947, 95%CI 1.361 to 11.450, P = 0.012), and no influencing factor was found in the observation group. ConclusionAmong the patients with dysphagia after brainstem stroke, less accompanying disorders and more severe dysphagia were found in those with cricopharyngeal achalasia. All patients improved in dysphagia after treatment, and the rehabilitation effect of cricopharyngeal achalasia was better. The score of DSS relates with oral feeding in non-cricopharyngeal achalasia patients, and there was no specific influencing factor in cricopharyngeal achalasia patients.

Medication guidelines for glucagon-like peptide-1 receptor agonist （2023 edition） / 中国药房

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.

The assessment value of endothelial glycocalyx degradation products in pulmonary edema patients with acute respiratory distress syndrome / 中华急诊医学杂志

Objective:To investigate the application of endothelial glycocalyx degradation products in assessing the severity of pulmonary edema in patients with acute respiratory distress syndrome (ARDS).Methods:A prospective study was conducted to select patients diagnosed with ARDS at Wuxi People's Hospital from July 1, 2018 to December 31, 2019. The extravascular lung water index (EVLWI) was recorded within 2 h after admission by continuous cardiac output with pulse indicator. The indexes of glycocalyx degradation products syndecan-1 (SDC-1), heparan sulfate (HS), hyaluronic acid (HA) and the concentrations of inflammatory factors [blood tumor necrosis factor α (TNF-α), interleukin (IL)-6 and IL-10] were measured by enzyme-linked immunosorbent assay. Pearson correlation method was adopted to analyze the correlation of glycocalyx degradation products with EVLWI and inflammatory factors in ARDS patients. The patients were divided into the mild pulmonary edema group and severe pulmonary edema group according to EVLWI at the cut-off value of 10 mL/kg, and the differences of glycocalyx degradation products and inflammatory factors between the two groups were compared. Receiver operating characteristic (ROC) curve of the subjects were plotted to analyze the value of glycocalyx degradation products in determining the severity of pulmonary edema.Results:A total of 85 ARDS patients were enrolled. Pearson correlation analysis showed that SDC-1, HS, and HA were all positively correlated with IL-6, TNF-α, EVLWI (all P<0.05), but did not correlate with IL-10 (all P>0.05). Comparison of indicators between the mild pulmonary edema group (39 cases) and the severe pulmonary edema group (46 cases) showed that: IL-6[(33.63±3.43) ng/L vs. (39.99±4.64) ng/L], TNF-α[(43.38±6.05) ng/L vs. (50.79±7.35) ng/L], SDC-1[(494.13±47.23) ng/L vs. (563.50±56.36) ng/L], HS[(114.02±18.39) ng/mL vs. (138.93±17.02) ng/mL], and HA[(441.44±62.52) ng/mL vs. (546.23±85.24) ng/mL] were statistically different between the two groups(all P<0.05). Whereas, IL-10 [(24.37±10.11) ng/L vs. (28.75±11.98) ng/L] was not statistically different between the two groups ( P>0.05). ROC curve analysis showed that the combined prediction of SDC-1, HA and HS indicators was superior to the single indicator. The area under the ROC curve combining the three indicators was 0.928 (95% CI: 0.872-1.000), with a sensitivity and specificity of 87.5% and 86.7%, respectively. Conclusions:There is a positive correlation between glycocalyx degradation products SDC-1, HS, HA and EVLWI in ARDS patients. The application of these three glycocalyx degradation products can be used as a reliable indicators for judging the severity of pulmonary edema in ARDS patients.

Effects of rhGLP-1 (7-36) on Akt/GSK3 signaling pathway in hepatocytes / 中华内分泌外科杂志

Objective:To observe the effect of rhGLP-1 (7-36) on Akt/GSK3 signaling pathway in hepatocytes.Methods:Human HL7702 cell line was cultured to the logarithmic growth stage and divided into experimental group and blank control group. The cultures were incubated with 100nM medium containing rhglp-1 (7-36) and without rhglp-1 (7-36) for 90min. The levels of Akt, Glycogen synthase Kinase 3 (GSK3) and Glycogen synthase (GS) in the two groups were detected by Western Blot.Results:Compared with blank control group, the protein expression of p-Akt (Thr308) in experimental group (1.81±0.28) was significantly increased ( P=0.01), but the protein expression of Akt and p-Akt (Ser473) was not significantly changed. The protein expression levels of p-GSK3α (Ser21) (1.27±0.09) and p-GSK3β (Ser9) (1.24±0.09) in the experimental group were significantly increased ( P=0.003, 0.002), while the protein expression levels of GSK3α and GSK3β were not significantly changed. The protein expression level of p-GS (Ser641) (0.70±0.16) was decreased in the experimental group ( P=0.03), but the protein expression level of GS did not change significantly. Conclusion:Glp-1 can inhibit GSK3/GS signaling pathway, activate GS activity and promote glycogen synthesis.

Value of 125I seed implantation for patients with oligometastatic EGFR-mutant non-small cell lung cancer without progression after first-line EGFR-TKIs treatment / 中华核医学与分子影像杂志

Objective:To explore the clinical efficacy of CT-guided 125I seed implantation in patients with oligometastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) activating mutations (EGFRm+ ) without progression after first-line EGFR-tyrosine kinase inhibitors (TKIs) treatment. Methods:From January 2015 to January 2019, 89 eligible patients (38 males, 51 females; age: (62±11) years) in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. They were divided into 2 groups according to different treatment methods. The 125I seeds were implanted for oligometastatic lesions and/or primary tumors without progression after first-line EGFR-TKIs therapy in local consolidation treatment group (Group A, n=32). The maintenance treatment group (Group B, n=57) only received EGFR-TKIs until disease progression. The progression-free survival (PFS) and overall survival (OS) of the 2 groups were estimated by Kaplan-Meier curves, and were compared by using log-rank test. Complications in Group A were observed. Results:The follow-up time of the group A and group B were 36.5(31.0, 43.3) months and 30.0(24.0, 35.0) months respectively. The median PFS and OS in group A were 15.0(95% CI: 12.8-17.2 ) months and 37.0(95% CI: 33.9-40.1) months, both of which were significantly longer than those in group B (12.0(95% CI: 10.9-13.1) months and 31.0(95% CI: 28.9-33.1) months; χ2 values: 8.80, 7.15, P values: 0.003, 0.007). In Group A, the total incidence of complications in CT-guided 125I seed implantation was 21.9%(7/32), and the common complications and adverse events were pneumothorax and hemoptysis. Only 1 patient underwent chest tube insertion, and the rest were treated with conservative treatment. No operation related death occurred. Conclusion:CT-guided 125I seed implantation is safe and feasible for patients with EGFRm+ oligometastatic NSCLC without progression after first-line EGFR-TKIs treatment, and can prolong the PFS and OS of patients.

A single center survey and analysis on the psychological stress status and influencing factors of medical staff / 中华健康管理学杂志

Objective:To investigate and analyze the psychological stress status and influencing factors of medical staff in comprehensive grade A hospitals.Methods:This was a cross-sectional survey using a convenient sampling method. A questionnaire survey was conducted among 2 048 staff members of the Affiliated Hospital of Qingdao University from February 25 to June 16, 2022. The questionnaires included the Self-rating Stress Questionnaire (SSQ-53), the Self-rating Anxiety Scale, and the Self-rating Depression Scale. A total of 2 048 questionnaires were distributed and 2 048 were collected. Among them, 2 006 (97.95%) were valid questionnaires, and 2 006 medical staff were ultimately included in the analysis. According to the results of the scale, they were divided into the increased psychological stress group and the non increased psychological stress group. Descriptive analysis, independent sample t-test/chi-square test, correlation analysis, and other methods were used to analyze the psychological stress status of medical staff and the distribution of related factors, and multivariate logistic regression was used to analyze their influencing factors. Results:A total of 310 (15.5%) out of 2 006 study subjects showed increased psychological stress. Women had a statistically significant increase in physical (14.7% vs 8.0%, χ2=12.40, P<0.001) and emotional dimensions (18.2% vs 13.5%, χ2=5.04, P=0.025) of stress compared to men. The level of psychological stress was positively correlated with anxiety and depression ( r=0.810, 0.749, respectively, P<0.001). Univariate analysis showed that those who were women ( χ2=6.76, P=0.009), with low education backgrounds ( Z=-2.50, P=0.012), nurses ( χ2=15.72, P<0.001), or working in emergency departments ( χ2=13.64, P=0.009) had a higher rate of increased psychological stress, while the serum calcium level in the increased psychological stress group was lower than that in the non increased psychological stress group ( t=2.82, P=0.005). Multivariate analysis showed that low educational backgrounds ( OR=2.238, 95% CI: 1.090-4.597, P=0.028) and working in emergency department ( OR=1.589, 95% CI: 1.012-2.493, P=0.044) were independent risk factors for increased psychological stress of medical staff. Working in administrative and logistics departments ( OR=0.466, 95% CI: 0.229-0.950, P=0.036) and serum calcium level ( OR=0.213, 95% CI: 0.059-0.760, P=0.017) were negatively correlated with increased psychological stress. Conclusions:In comprehensive grade A hospitals, medical staff working in the emergency department or with lower educational backgrounds face greater psychological stress. Serum calcium level is negatively correlated with increased psychological stress, but the causal relationship needs further study.

Predictive value of serum neutrophil gelatinase-associated lipocalin for acute kidney injury in high-risk elderly patients / 中华老年医学杂志

Objective:To analyze the predictive value of neutrophil gelatinase-associated lipocalin(NGAL)in high-risk elderly patients with acute kidney injury(AKI).Methods:A retrospective study was conducted to collect 183 patients over 65 years old in the Department of Geriatrics, the First Affiliated Hospital of Nanjing Medical University from January 2018 to October 2019.The patients were combined with at least one risk factor.The diagnostic effect of NGAL for AKI prediction in high-risk patients was evaluated.According to the initial serum creatinine(SCr)and basic glomerular filtration rate(eGFR), the patients were divided into chronic kidney disease(CKD)group and non-CKD group.The optimal diagnostic threshold for A-on-C is determined by determining the area under the subject curve(AuROC). Univariate and independent predictors multivariate regression analysis was used to assess the risk of AKI.Results:The serum NGAL(NGAL)level in AKI group was higher than that in non-AKI group[702.5 μg/L(499.2, 813.2) vs.233.9 μg/L(147.2, 315.7), Z=8.002, P<0.001]. In CKD patients, serum NGAL in AKI group was higher than that in non-AKI group[1033 μg/L(845.5, 1447) vs.288.2 μg/L(221.4, 423.3), Z=4.867, P<0.001]. In all patients, model 3 with four variables showed better AKI prediction ability than model 0, 1 and 2( R2=0.743, P<0.001). In the CKD group, the AuROC of serum NGAL for AKI prediction was larger than that of CYS-C group, whereas in the non-CKD group, the AuROC of serum NGAL for AKI prediction was smaller than that of CYS-C group. Conclusions:Serum NGAL may serve as a useful biomarker for AKI prediction in AKI high-risk elderly patients.Especially in patients with CKD, Serum NGAL has a better predictive value for AKI than traditional indicators.

A comparative study on the success rate and safety between computed tomography-guided gastrostomy and endoscopic gastrostomy / 中华消化杂志

Objective:To compare and analyze the technical success rate and safety between computed tomography(CT)-percutaneous radiological gastrostomy (PRG) and percutaneous endoscopic gastrostomy (PEG).Methods:From January 2017 to January 2022, at the First Affiliated Hospital of Zhengzhou University, the data of 76 patients who underwent gastrostomy due to inability to eat orally were collected, including 38 patients in PEG group and 38 patients in CT-PRG group. Surgical outcomes and complications were compared between the PEG and CT-PRG groups. Surgical outcomes included technical success rate, operation time, postoperative body mass index and hospital stay; while complications included minor complications (such as perifistula infection, granulation tissue proliferation, leakage, pneumoperitoneum, fistula tube obstruction, fistula tube detachment and persistent pain) and serious complications (such as bleeding, peritonitis, colonic perforation and death within 30 d). Independent sample t test, chi-square test, and Fisher exact probability test were used for statistical analysis. Results:The technical success rate of CT-PRG group was higher than that of the PEG group (100.0%, 38/38 vs. 78.9%, 30/38), and the operation time was shorter than that of the PEG group ((17.16±8.52) min vs. (29.33±16.22) min), and the differences were statistically significant ( χ2=1.19, t=2.36; P=0.038 and 0.011). There were no significant differences in postoperative body mass index ((16.29±3.56) kg/m 2 vs. (16.12±3.17) kg/m 2) and hospital stay ((4.13±1.26) d vs. (3.52±1.13) d) between PEG group and CT-PRG group (both P>0.05). The incidence of minor complications in the PEG group was 42.1% (16/38), including 6 cases of perifistulal infection, 1 case of leakage, 5 cases of fistula tube obstruction, 1 case of fistula tube detachment, and 3 cases of persistent pain. The incidence of serious complications was 5.3% (2/38), including 1 case of bleeding and 1 case of colonic perforation. The incidence of minor complications in the CT-PRG group was 39.5% (15/38), including 5 cases of perifistula infection, 1 case of granulation tissue proliferation, 3 cases of pneumoperitoneum, 3 cases of fistula tube obstruction, 2 cases of fistula tube detachment, and 1 case of persistent pain. The incidence of serious complications was 0. There was no significant difference in the incidence of minor complications between the PEG group and the CT-PRG group ( P>0.05), while the incidence of serious complications in the CT-PRG group was lower than that of the PEG group, and the difference was statistically significant (Fisher exact probability test, P=0.043). Conclusion:PEG is a safe and effective method of gastrostomy, but for patients with esophageal obstruction, CT-PRG can be an effective supplement to PEG.