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.

To explore the value of portable oto-endoscopy system in clinical teaching of otolaryngology residents.

To explore the value of portable oto-endoscopy system in clinical teaching of otolaryngology residents.

Objective:To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV).Methods:A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA).Results:Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29(34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance.Conclusion:NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.

Objectives:To evaluate the association between estimated pulse wave velocity(ePWV)and risk of new-onset diabetes. Methods:A total of 82 440 employees without prior diabetes who participated in the health examination from July 2006 to October 2007 were selected as the observation cohort,participants were followed-up for a mean of(13.19±3.73)years.The study population was divided into four groups according to the ePWV quartiles:group Q1(ePWV<12.35 m/s,n=20 610),group Q2(12.35 m/s≤ePWV<13.74 m/s,n=20 610),group Q3(13.74 m/s≤ePWV<15.16 m/s,n=20 611),and group Q4(ePWV≥15.16 m/s,n=20 609).ROC curve was used to analyze the predictive value of ePWV for new-onset diabetes.The incidence density of diabetes in each group was calculated.After adjustment for the traditional cardiovascular risk factors(including sex,smoking,drinking,exercise,education level,family history of cardiovascular disease,history of myocardial infarction,history of stroke,body mass index,total cholesterol,fasting blood glucose,uric acid and high-sensitivity C-reactive protein),multivariate Cox regression models were used to evaluate the association between ePWV and risk of new-onset diabetes. Results:The area under the ROC curve of ePWV was 0.60 in the prediction of new-onset diabetes,and the optimal cut-offvalue was 12.78 m/s.With the increase of ePWV quartile,the incidence density of diabetes showed an increasing trend,which was 5.84/1 000 person years,12.04/1 000 person years,15.70/1 000 person years and 16.87/1 000 person years,respectively.After adjusting for the traditional cardiovascular risk factors,the risk of new onset diabetes increased by 9%(HR=1.09,95%CI:1.08-1.11,P<0.01)for each 1 m/s increase in ePWV.Subgroup analysis showed that higher ePWV was significantly associated with increased risk of new-onset diabetes regardless of presence or absence of cardiovascular risk factors,male or female,and age<51 years or age≥51 years,with the HR(95%CI)values of 1.07(1.05-1.08)and 1.21(1.08-1.36),1.07(1.06-1.09)and 1.17(1.15-1.20),1.22(1.19-1.24)and 1.06(1.04-1.07). Conclusions:ePWV has a certain predictive value for new-onset diabetes and is an independent risk factor for new-onset diabetes.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Venlafaxine (VEN) is a new antidepressant drug that can effectively antagonize the reuptake of serotonin (5-HT) and norepinephrine (NE), compared with other antidepressants, venlafaxine pharmacokinetics / pharmacodynamics (PK-PD) is more regular and has the characteristics of less toxic side effects, fast oral absorption, and high bio-availability. This article reviews the PK-PD model-ling of venlafaxine and its quantitative relationship, as well as the factors affecting the process in vivo of venlafaxine, including sex, body weight, individual genotype, liver and kidney function impairment, drug-drug interaction and other related factors.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.