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.

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.

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.

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.

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.

Pricking and cupping at Jianbo area combined with conventional acupuncture for scapulohumeral periarthritis of frozen stage: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of conventional acupuncture combined with pricking and cupping at Jianbo area and conventional acupuncture in the treatment of scapulohumeral periarthritis of frozen stage.@*METHODS@#A total of 66 patients with scapulohumeral periarthritis of frozen stage were randomly divided into a combination group (31 cases) and an acupuncture group (35 cases, 1 case dropped off). Both groups were given functional exercise. Patients in the acupuncture group were treated with acupuncture at Jianyu (LI 15), Jianliao (TE 14), Binao (LI 14) and ashi point on the affected side, once every other day, three times a week, for a total of 4 weeks. On the basis of treatment in the acupuncture group, the patients in the combination group were treated with pricking and cupping at Jianbo area (the area surrounded by the 3 acupoints of Tianzong [SI 11], Naoshu [SI 10] and Jianzhen [SI 9]), once a week for 4 weeks. The University of California-Los Angeles (UCLA) shoulder joint score, visual analogue scale (VAS) score before treatment, after treatment and after 6 months of treatment completion (follow-up) and tenderness threshold before and after treatment, and the clinical effects of the two groups after treatment and in follow-up were evaluated.@*RESULTS@#In the two groups, after treatment and in follow-up, the UCLA shoulder joint scores were higher than those before treatment (P<0.05), and the VAS scores were lower than those before treatment (P<0.05). In the combination group, after treatment and in follow-up, the UCLA shoulder joint score was higher than that of the acupuncture group (P<0.05), and the VAS score was lower than that of the acupuncture group (P<0.05). After treatment, the tenderness thresholds of the two groups were higher than those before treatment (P<0.05), and the tenderness threshold in the combination group was higher than that in the acupuncture group (P<0.05). After treatment and in follow-up, the cured and markedly effective rate of the combination group was 48.4% (15/31) and 51.6% (16/31) respectively, which was higher than 23.5% (8/34) and 23.5% (8/34) of the acupuncture group (P<0.05).@*CONCLUSION@#Pricking and cupping in Jianbo area combined with conventional acupuncture can improve shoulder joint function and relieve shoulder joint pain in patients with scapulohumeral periarthritis of frozen stage, and the curative effect is better than that of single conventional acupuncture.

The curative effect and mechanism of magnetic hyperthermia in the treatment of knee osteoarthritis / 西安交通大学学报(医学版)

【Objective】 We combined the concept of traditional medicine with magnetic induction technology, originally brought up the research concept of magnetic hyperthermia to cure KOA, explored the mechanism and constructed a new treatment of KOA with modern medical features. 【Methods】 Through establishing a primary KOA model in rats and constructing ferrimagnetic vortex domain iron oxide nanorings (FVIOs) as a platform for highly efficient magnetic hyperthermia agent, the lesions of KOA were heated accurately under the low-intensity magnetic field. We confirmed the curative effect through the results of pain perception, histopathology, knee joint morphology and microscopic bone structure and the content of serum inflammatory factor, to study the therapeutic mechanism of magnetic hyperthermia for KOA. 【Results】 Compared with the model group, the recovery of mechanical pain threshold after magnetic hyperthermia improved by approximately 48.9%; the degree of hyperemia and edema of joint capsule and synovial tissue and the wear degree of joint cartilage surface, were significantly reduced; the Mankin and OARSI scores decreased by about 33% and 20%, respectively; the MicroCT results indicated that the degree of hardening of the subchondral bone also improved; the expression of inflammatory factors in the serum was reduced. 【Conclusion】 In this study, we utilized the FVIOs as a high-efficiency magnetic hyperthermia platform for the treatment of KOA. The efficacy of magnetic hyperthermia on KOA is clarified, and the mechanism is related to the inhibition of inflammatory factors.

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.

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.

An MRI study of lateral vascular safety zones in oblique lumbar interbody fusion surgery / 中国修复重建外科杂志

OBJECTIVE@#To study the anatomical characteristics of blood vessels in the lateral segment of the vertebral body through the surgical approach of oblique lumbar interbody fusion (OLIF) using MRI imaging, and evaluate its potential vascular safety zone.@*METHODS@#The lumbar MRI data of 107 patients with low back and leg pain who met the selection criteria between October 2019 and November 2022 were retrospectively analyzed. The vascular emanation angles, vascular travel angles, and the length of vessels in the lateral segments of the left vertebral body of L 1-L 5, as well as the distance between the segmental vessels in different Moro junctions of the vertebral body and their distances from the edges of the vertebrae in the same sequence (bottom marked as I, top as S) were measured. The gap between the large abdominal vessels and the lateral vessels of the vertebral body was set as the lateral vascular safe zones of the lumbar spine, and the extent of the safe zones (namely the area between the vessels) was measured. The anterior 1/3 of the lumbar intervertebral disc was taken as the simulated puncture center, and the area with a diameter of 22 mm around it as the simulated channel area. The proportion of vessels in the channel was further counted. In addition, the proportions of segmental vessels at L 5 without a clear travel and with an emanation angel less than 90° were calculated.@*RESULTS@#Except for the differences in the vascular emanation angles between L 4 and L 5, the vascular travel angles between L 1, L 2 and L 4, L 5, and the length of vessels in the lateral segments of the vertebral body among L 1-L 4 were not significant ( P>0.05), the differences in the vascular emanation angles, vascular travel angles, and the length of vessels between the rest segments were all significant ( P<0.05). There was no significant difference in the distance between vessels of L 1, L 2 and L 2, L 3 at Moro Ⅰ-Ⅳ junctions ( P>0.05), in L 3, L 4 and L 4, L 5 at Ⅱ and Ⅲ junction ( P>0.05). There was no significant difference in the vascular distance of L 2, L 3 between Ⅱ, Ⅲ junction and Ⅲ, Ⅳ junction, and the vascular distance of L 3, L 4 between Ⅰ, Ⅱ junction and Ⅲ, Ⅳ junction ( P>0.05). The vascular distance of the other adjacent vertebral bodies was significant different between different Moro junctions ( P<0.05). Except that there was no significant difference in the distance between L 2I and L 3S at Ⅰ, Ⅱ junction, L 3I and L 4S at Ⅱ, Ⅲ junction, and L 2I and L 3S at Ⅲ, Ⅳ junction ( P>0.05), there was significant difference of the vascular distance between the bottom of one segment and the top of the next in the other segments ( P<0.05). Comparison between junctions: Except for the L 3S between Ⅰ, Ⅱ junction and Ⅱ, Ⅲ junction, and L 5S between Ⅰ, Ⅱ junction and Ⅱ, Ⅲ and Ⅲ, Ⅳ junctions had no significant difference ( P>0.05), there were significant differences in the distance between the other segmental vessels and the vertebral edge of the same sequence in different Moro junctions ( P<0.05). The overall proportion of vessels in the simulated channels was 40.19% (43/107), and the proportion of vessels in L 1 (41.12%, 44/107) and L 5 (18.69%, 20/107) was higher than that in the other segments. The proportion of vessels in the channel of Moro zone Ⅰ (46.73%, 50/107) and zone Ⅱ (32.71%, 35/107) was higher than that in the zone Ⅲ, while no segmental vessels in L 1 and L 2 were found in the channel of zone Ⅲ ( χ 2=74.950, P<0.001). Moreover, 26.17% (28/107) of the segmental vessels of lateral L 5 showed no movement, and 27.10% (29/107) vascular emanation angles of lateral L 5 were less than 90°.@*CONCLUSION@#L 1 and L 5 segmental vessels are most likely to be injured in Moro zones Ⅰ and Ⅱ, and the placement of OLIF channels in L 4, 5 at Ⅲ, Ⅳ junction should be avoided. It is usually safe to place fixation pins at the vertebral body edge on the cephalic side of the intervertebral space, but it is safer to place them on the caudal side in L 1, 2 (Ⅰ, Ⅱ junction), L 3, 4 (Ⅲ, Ⅳ junction), and L 4, 5 (Ⅱ, Ⅲ, Ⅳ junctions).

Comparison of big data before and after the establishment of one-stop intravitreal injection mode in the real-world research / 中华眼底病杂志

Objective:To compare and analyze the application of anti-vascular endothelial growth factor (VEGF) drugs for intravitreal injection in the real world before and after the establishment of one-stop intravitreal injection center, as well as the advantages and disadvantages of different management modes.Methods:A retrospective clinical study. A total of 4 015 patients (4 659 eyes) who received anti-VEGF drugs for ocular fundus diseases at the Tianjin Medical University Eye Hospital from July, 2018 to June, 2022 were included in the study. There were 2 146 males and 1 869 females. The ocular fundus diseases in this study were as follows: 1 090 eyes of 968 patients with wet age-related macular degeneration (wAMD); 855 eyes of 654 patients with diabetic macular edema (DME); 1 158 eyes of 980 patients with diabetic retinopathy (DR); 930 eyes of 916 patients with macular edema secondary to retinal vein occlusion (RVO-ME). A total of 294 eyes of 275 patients with choroidal neovascularization secondary to pathological myopia (PM-CNV); 332 eyes of 222 patients with other fundus diseases. A total of 13 796 anti-VEGF needles were injected. A total of 1 252 patients (1 403 eyes) from July 2018 to June 2020 were regarded as the control group. From July 2020 to June 2022, 2 763 patients (3 256 eyes) who received anti-VEGF treatment in the intravitreal injection center were regarded as the observation group. The total number of intravitreal injection needles, the distribution of anti-VEGF therapy in each disease according to disease classification, the proportion of patients who chose the 3+ on-demand treatment (PRN) regimen and the distribution of clinical application of different anti-VEGF drugs were compared between the control group and the observation group. The waiting time and medical experience of patients were investigated by questionnaire. χ2 test was used to compare the count data between the two groups, and t test was used to compare the measurement data. Results:Among the 13 796 anti-VEGF injections in 4 659 eyes, the total number of anti-VEGF drugs used in the control and observation groups were 4 762 and 9 034, respectively, with an average of (3.39±3.78) and (2.78±2.27) injections per eye ( t=6.900, P<0.001), respectively. In the control and observation groups, a total of 1 728 and 2 705 injections of anti-VEGF drugs were used for wAMD with an average of (5.14±4.56) and (3.59±2.45) injections per eye, respectively; a total of 982 and 2 038 injections of anti-VEGF drugs were used for DME with an average of (4.36±4.91) and (3.24±2.77) needles per eye, respectively. Additionally, a total of 942 and 2 179 injections of anti-VEGF drugs were injected for RVO-ME with an average of (3.98±3.71) and (3.14±2.15) injections per eye, respectively; a total of 291 and 615 injections of anti-VEGF drugs were injected for PM-CNV with an average of (3.31±2.63) and (2.99±1.69) injections per eye, respectively. A total of 683 and 1 029 injections of anti-VEGF drugs were injected for DR with an average of (1.60±1.26) and (1.41±1.05) injections per eye, respectively. The clinical application and implementation of "3+PRN" treatment were as follows: 223 (66.4%, 223/336) and 431 eyes (57.2%, 431/754) in the wAMD ( χ2=8.210, P=0.004), 75 (33.3%, 75/225) and 236 (37.5%, 236/630) eyes in the DME ( χ2=1.220, P>0.05), and 97 (40.9%, 97/237) and 355 eyes (51.2%, 355/693) in the RVO-ME ( χ2=7.498, P=0.006), 39 (44.3%, 39/88) and 111 eyes (53.9%, 111/206) in the PM-CNV ( χ2=2.258, P>0.05), respectively. In addition, the results of the questionnaire survey showed that there were significant differences between the control and observation groups regarding the time of appointment waiting for surgery ( t=1.340), time from admission to entering the operating room on the day of injection ( t=2.780), time from completing preoperative treatment preparation to waiting for entering the operating room ( t=8.390), and time from admission to discharge ( t=6.060) ( P<0.05). Conclusions:The establishment of a one-stop intravitreal injection mode greatly improved work efficiency and increased the number of injections. At the same time, the compliance, waiting time, and overall medical experience of patients significantly improved under centralized management.

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.

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 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.

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.

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.

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 electroacupuncture with different frequencies on hippocampal neuronal apoptosis and JNK signaling pathway in rats with vascular dementia / 针灸推拿医学（英文版）

Objective: To observe the effects of electroacupuncture (EA) with three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) on the apoptosis of neurons and c-Jun N-terminal kinase (JNK) signaling pathway in the hippocampus of rats with vascular dementia (VD), and explore the mechanism of EA intervention for VD. Methods: Fifty male Sprague-Dawley rats were randomly divided into a model group, a sham operation group, a 100 Hz EA group, a 2 Hz EA group, and a 2 Hz/100 Hz EA group, with ten rats in each group. The VD model rats were established by repeated ischemia-reperfusion of bilateral common carotid arteries. The rats in the EA groups received EA intervention at Baihui (GV20), Dazhui (GV14), Geshu (BL17) and Zusanli (ST36), once a day for 14 d. Afterward, Morris water maze was used to examine the learning and memory performances of the rats in each group, hematoxylin-eosin staining to observe the histomorphological changes in the hippocampal CA1 region, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling to test the apoptosis of neurons in the hippocampal CA1 region, and Western blot to detect the protein expression levels of JNK, phosphorylated JNK (p-JNK), Caspase-8, and Caspase-3 in the hippocampus tissue. Results: Compared with the sham operation group, the escape latency of the model group in water maze test was prolonged; the number of crossing the original platform was decreased (P<0.01); the hippocampal neurons were severely damaged and the number of surviving neurons was decreased (P<0.01), whereas the number of apoptotic neurons was increased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were significantly increased (P<0.01). Compared with the model group, the escape latency of each EA group was significantly shortened; the number of crossing the original platform was significantly increased (P<0.01); the damage of hippocampal neurons was alleviated, the number of surviving neurons was increased (P<0.01), and the number of apoptotic neurons was decreased (P<0.01); the protein expression levels of JNK, p-JNK, Caspase-8, and Caspase-3 in the hippocampus were decreased (P<0.01). The results in the 2 Hz EA group and the 2 Hz/100 Hz EA group were superior to those in the 100 Hz EA group. Conclusion: EA with the three frequencies (100 Hz, 2 Hz, and 2 Hz/100 Hz) can improve the learning and memory performances in VD rats subjected to ischemia-reperfusion, its mechanism may be related to the inhibition of neuronal apoptosis and the regulation of the related protein expression of JNK signaling pathway, and the intervention effects of EA with 2 Hz and 2 Hz/100 Hz are more significant.

Efficacy of second session of endoscopic ultrasound-guided lauromacrogol ablation for pancreatic cystic neoplasms / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of the second session of endoscopic ultrasound-guided lauromacrogol ablation (EUS-LA) for pancreatic cystic neoplasms (PCNs).Methods:A total of 74 patients with suspected of PCNs who underwent EUS-LA in the First Medical Center of Chinese PLA General Hospital from April 2015 to December 2020 were enrolled in the study. Fifteen of them underwent the second ablation. The efficiency of EUS-LA was determined based on the change of lesion volume during the imaging follow-up, categorized into complete resolution (CR), partial resolution (PR) and stable disease (SD). The safety was determined by the complication incidence.Results:Among the 15 patients undergoing the second EUS-LA, there were 9 males and 6 females with age of 51.5±17.6 years. Thirteen patients completed imaging follow-up after the second EUS-LA, CR was achieved in 8 patients, PR in 2 patients and 3 in SD. The CR rate increased from 0 after the first ablation to 8/13 after the second ablation ( P=0.002). The median cyst diameter decreased from 22.0 mm before the second ablation to 15.0 mm after the second ablation ( Z=-2.666, P=0.008) and the median cyst volume reduced from 2 419.7 mm 3 to 1 099.5 mm 3 ( Z=-2.134, P=0.033). The complication incidence of the second ablation was 2/15, similar to that of the first ablation. Conclusion:The second ablation is effective and safe without increasing the complication incidence in patients without achieving CR after the first EUS-LA.

Role of dermoscopy in assessing vitiligo activity / 中华皮肤科杂志

With in-depth research and development of dermoscopy, the dermoscopic features including perifollicular pigments, perilesional pigments, pigment network structure, satellite phenomenon and "tapioca sago" appearance, micro-Koebner phenomenon and comet tail-like phenomenon have provided a basis for the evaluation of vitiligo activity. This review summarizes progress in the evaluation of vitiligo activity with dermoscopy in recent years, aiming to promote the application of dermoscopy in the assessment of vitiligo activity.