Diabetic nephropathy is the most serious complication of diabetes and a major cause of end-stage renal disease worldwide.Although hyperglycaemia is widely considered to be the main driving force for the progression of diabetic nephropathy to end-stage renal disease,inflammatory signaling pathways and inflammatory cells also play important roles in the pathogenesis and progression of the disease.Therefore,treatment strategies targeting the inflammation-related intracellular signaling pathways may become a new direction for the treatment of diabetic nephropathy.Currently,the development of anti-inflammatory drugs for diabetic nephropathy is also underway,and they have shown promising results in experimental models.This article focuses on the connection between inflammatory cells and inflammatory signaling pathways and diabetic nephropathy,as well as the current research progress on targeted anti-inflammatory treatment.

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective:To investigate the correlation between pulmonary arteriovenous fistula (PAVF) and ischemic stroke, and to improve the diagnosis and treatment of embolic strokes of undetermined source.Methods:Five patients with ischemic stroke caused by PAVF admitted to Xiangya Hospital of Central South University from January 2017 to December 2020 were collected. The diagnosis, treatment and prognosis of stroke caused by PAVF were summarized based on literature review.Results:Among the 5 patients, 1 is male and 4 are females, with age of (34.4±9.3) years. Weakness of unilateral limb, slurred speech, vision changes, drooping eyelids, etc., were the first manifestations of stroke. The location of cerebral infarction was indefinite. In this study, 5 patients were all isolated PAVF, including 3 cases of left lower lung, 1 case of left upper lung and 1 case of right lower lung. All 5 patients underwent interventional therapy, were followed-up for 6 months and 12 months after surgery, and none of them had a new stroke attack, and only 1 case had recanalization of PAVF.Conclusions:PAVF is a rare vascular lesion, stroke caused by which is even rarer, with a lack of specificity in clinical manifestations. For young patients with unexplained embolic stroke, if the stroke has a sudden onset, the anterior and posterior circulation can be involved, and multiple vascular distribution regions are often involved, and it is difficult to find a clear emboli basis, with manifestations such as hypoxemia, PAVF should be considered. Percutaneous catheter intervention for PAVF is safe and effective, and is the preferred method for the treatment of PAVF.

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

Baylisascaris schroederi,a roundworm(ascaridoid)parasite specific to the bamboo-feeding giant panda(Ailuropoda melanoleuca),represents a leading cause of mortality in wild giant panda populations.Here,we present a 293-megabase chromosome-level genome assembly of B.schroederi to infer its biology,including host adaptations.Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations,suggesting their potential for transmission and rapid adaptation to new hosts.Genomic and anatomical lines of evidence,including expansion and positive selection of genes related to the cuticle and basal metabolisms,indicate that B.schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism.Additionally,we characterized the secretome of B.schroederi and predicted potential drug and vaccine targets for new control strategies.Overall,this genome resource provides new insights into the host adaptation of B.schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages.Our findings on the unique biology of B.schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism.

Enzalutamide (ENZ) is a second-generation androgen receptor (AR) antagonist used for the treatment of castration-resistant prostate cancer (CRPC) and reportedly prolongs survival time within a year of starting therapy. However, CRPC patients can develop ENZ resistance (ENZR), mainly driven by abnormal reactivation of AR signaling, involving increased expression of the full-length AR (ARfl) or dominantly active androgen receptor splice variant 7 (ARv7) and ARfl/ARv7 heterodimers. There is currently no efficient treatment for ENZR in CRPC. Herein, a small molecule LLU-206 was rationally designed based on the ENZ structure and exhibited potent inhibition of both ARfl and constitutively active ARv7 to inhibit PCa proliferation and suppress ENZR in CRPC. Mechanically, LLU-206 promoted ARfl/ARv7 protein degradation and decreased ARfl/ARv7 heterodimers through mouse double minute 2-mediated ubiquitination. Finally, LLU-206 exhibited favorable pharmacokinetic properties with poor permeability across the blood-brain barrier, leading to a lower prevalence of adverse effects, including seizure and neurotoxicity, than ENZ-based therapies. In a nutshell, our findings demonstrated that LLU-206 could effectively inhibit ARfl/ARv7-driven CRPC by dual-targeting of ARfl/ARv7 heterodimers and protein degradation, providing new insights for the design of new-generation AR inhibitors to overcome ARfl/ARv7-driven CRPC.

Based on the latest results of international researches, combining with the experiences of our team in the simulation of acute dyspnea, Xiangya Hospital Central South University has summarized 7 characteristics, procedures and methods of debriefing, including that immediate feedback happens after simulation; feedback is provided by a trained instructor with clinical experience; feedback time is at least longer than the simulation time; various international methods of feedback can be used; the content of feedback is the learning objective; oral feedback is preferred; video can be used to review the details. The study aims to provide a theoretical basis for debriefing in domestic scenario stimulation teaching, and finally improve the effectiveness of the scenario stimulation teaching.

Objective:To investigate the effects of airway humidification therapy on pertussis in infants.Methods:Sixty children with pertussis who received treatment in Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2020 to September 2021 were included in this study. They were randomly divided into study and control groups, with 30 infants per group. The control group was treated with conventional drugs. The study group was subjected to airway humidification therapy based on conventional drug treatment. Clinical efficacy was evaluated in each group. Time to an improvement in clinical symptoms and length of hospital stay were recorded. Lung function indicators and serum inflammatory factor levels were determined before and after treatment. Pertussis-related complications were recorded.Results:The overall response rate in the study group was significantly higher than that in the control group (100.00% vs. 76.7%, χ2 = 5.82, P = 0.016). Time to disappearance of spastic cough, time to resolution of cyanosis, time to disappearance of pulmonary rales, and length of hospital stay in the study group were (3.10 ± 0.67) days, (1.53 ± 0.68) days, (4.27 ± 0.58) days, and (11.57 ± 0.73) days, respectively, which were significantly shorter than (4.23 ± 1.99) days, (2.67 ± 1.77) days, (5.63 ± 2.38) days, (13.33 ± 2.40) days ( t = 2.93, 3.27, 3.04, 3.86; P = 0.005, 0.002, 0.003, P < 0.001). Respiratory rate in the study group was significantly lower than that in the control group [(21.83 ± 1.15) breaths/minute vs. (24.23 ± 3.12) breaths/minute, t = 3.94, P = 0.002]. Tidal volume/kg body weight, the ratio of time to peak expiratory flow to total expiratory time and the ratio of volume to peak expiratory flow to total expiratory volume in the study group were (10.70 ± 0.81) mL/kg, (41.60 ± 1.57)%, (42.89 ± 1.44)%, respectively, which were significantly higher than (9.78 ± 1.34) mL/kg, (39.18 ± 3.37)%, (40.20 ± 3.05)% in the control group ( t = 3.21, 3.56, 4.36; P < 0.001, P = 0.001, P < 0.001). Serum tumor necrosis alpha (TNF-α), interleukin-6 and interleukin-8 levels in the study group were (62.44 ± 2.96) ng/L, (46.59 ± 1.96) ng/L, (54.63 ± 3.27) ng/L, respectively, which were significantly lower than (79.86 ± 3.30) ng/L, (58.20 ± 2.10) ng/L, (63.31 ± 3.86) ng/L in the control group ( t =21.53, 22.13, 9.38, all P < 0.001). The overall incidence of pertussis in the study group was significantly lower than that in the control group (3.3% vs. 26.7%, χ2 = 4.71, P = 0.030). Conclusion:Airway humidification therapy can shorten the time to reduction of symptoms of spasmodic pertussis, improve clinical efficacy, strengthen pulmonary ventilation function, lower respiratory tract inflammatory responses and reduce the risk of pertussis-related complications.

Objective:To investigate the changes and clinical significance of white blood cell (WBC) count and polymorphonuclear cells (PMN) proportion of synovial fluid after primary total knee arthroplasty (TKA).Methods:A total of 59 patients (92 knees) who underwent TKA from April 2021 to July 2021 were included, including 13 males (20 knees) and 46 females (72 knees). The patients were with average age 65.17±7.49 years old (range 48-79) and with body mass index (BMI) 27.64±3.74 kg/m 2 (range 17-36 kg/m 2). There were 26 cases involved lateral knee and 33 cases bilateral knees. The left knee was involved in 46 knees, while other 46 were involved in right side. There were 54 patients diagnosed as osteoarthritis (84 knees) and 5 as rheumatoid arthritis (8 knees). None of the patients received antibiotics after hospitalization. Antibiotics were used prophylactically 30 min before surgery and after surgery. The synovial fluid WBC count and PMN proportion were detected during operation (It reflects the normal preoperative level) and on the 2nd, 5th and 35th day after operation. The changes of these indexes were analyzed. The unmixed synovial fluid was collected after the incision of the joint capsule during the operation. The outer upper edge of the patella was taken as the puncture point to extract the synovial fluid on the 2nd, 5th and 35th days after the operation. The final follow-up end point was a diagnosis of acute periprothetic joint infection (PJI) or 90 days of follow-up for patients without PJI. Results:After operation, the synovial fluid WBC count and PMN proportion showed a trend of increasing and then decreasing. The synovial fluid WBC count were 0.222(0.100, 0.567)×10 9/L, 20.011(14.573, 29.129)×10 9/L, 6.080(3.676, 8.797)×10 9/L, 0.533(0.394, 0.749)×10 9/L before surgery and at 2nd, 5th and 35th day after surgery respectively. The difference before and after operation was statistically significant (χ 2=247.343, P<0.001). The synovial fluid PMN proportion were 19.9%(15.0%, 30.0%), 96.0%(95.0%, 97.0%), 91.0%(89.0%, 93.0%) and 20.5%(15.6%, 26.9%) respectively and with significant difference (χ 2=242.521, P<0.001). Pairwise comparison of synovial fluid WBC count and PMN proportion before and on day 35 indicated no statistical significance ( P>0.05). However, the differences compared with that at other time points were statistically significant ( P<0.05). Conclusion:The synovial fluid WBC count and PMN proportion increased rapidly in the short term after TKA and then decreased to the preoperative level at varied rates. Referring to the Musculoskeletal Infection Society (MSIS) recommended threshold for diagnosing infection during the acute stress period (within 5 d postoperatively) can result in false positives. Recovery to preoperative levels at 35th days postoperatively can be used as a basis for ruling out early infection. Thus, early joint fluid PMN proportion may have more diagnostic value than WBC counts.

Objective:To investigate the impact of osteoporosis on clinical outcomes in elderly patients treated with short segment transforaminal lumbar interbody fusion.Methods:From May 2016 to May 2018, elderly patients who had undergone transforaminal lumbar interbody fusion(TLIF)in our hospital were retrospectively analyzed.Based on bone mineral density(BMD), patients were divided into the osteoporosis group(the OP group, n=75, T≤-2.5 in BMD)and the control group(the CO group, n=103, T>-1.0 in BMD). General patient information, clinical data and postoperative follow-up clinical results were compared between the two groups.Results:Eventually 178 cases were enrolled, including 68 with lumbar disc herniation and 110 with lumbar spinal stenosis.Preoperative Visual Analogue Scale(VAS)scores were 7.35±1.30 in the lower back and 7.32±1.30 in the leg for the OP group and 7.35±1.33 and 7.22±1.40, respectively, for the CO group, and there was no significant difference between the two groups( t=0.140 and 0.468, P=0.989 and 0.640). The proportions of cage collapse and internal fixation loosening were 70.7%(53/75)and 37.3%(28/75)in the OP group, which were higher than 22.3%(23/103)and 14.6%(15/103)in the CO group( χ2=41.440 and 12.280, both P=0.000). However, there was no significant difference between the OP group and the CO group in 1-and 2-year postoperative interbody fusion rates(postoperative 1-year rate: 89.3% or 67/75 vs.91.3% or 94/103, χ2=0.187, P=0.666; postoperative 2 year rate: 94.6% or 71/75 vs.95.1% or 98/103), χ2=0.021, P=0.885). There was no significant difference in VAS score and Oswestry disability index(ODI) between the OP group and the CO group at 6 months, 1 year and 2 years after surgery(all P>0.05). Conclusions:Although there are some osteoporosis-related complications such as cage subsidence and screw loosening, short-segment TLIF can still achieve good clinical results in elderly patients with osteoporosis.