ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

Aim To preliminarily evaluate the effects of hypobaric hypoxia on organism damage in rats with post-traumatic stress disorder(PTSD),with a view to laying a foundation for drug research in plateau PTSD.Methods The rats were randomly divided into four groups,namely,the control(Control)group,the sin-gle-prolonged stress(SPS)group,the hypobaric hy-poxia(HH)group and the single-prolonged stress combined with hypobaric hypoxia(SPS+HH)group.The PTSD model was firstly constructed using the SPS method for rats in the SPS and SPS+HH groups.On the second day,rats in the HH group and SPS+HH group were placed in a low-pressure hypoxia chamber at a simulated altitude of 6000 m for 14 days.General condition,behavior,blood tests,and histomorphology were examined in order to evaluate the damage caused by low pressure hypoxia in PTSD rats.Results The body mass of rats in the SPS+HH group was signifi-cantly reduced;the feces were partly hard and lumpy,and some of them were seen to have high viscosity.Anxiety-like and depression-like behaviors were ob-served in all groups except in the control group,in which hypobaric hypoxia aggravated the behavioral ab-normalities in SPS rats.Rats in both the SPS and SPS+HH groups had coagulation dysfunction and abnor-mally increased blood viscosity,which was significantly abnormal in the SPS+HH group;erythrocytes,hemo-globin,and erythrocyte specific volume in whole blood of rats in the SPS+HH group were significantly in-creased compared with those of rats in the SPS group;and serum TP,LDH and GLU levels were abnormal in rats in the SPS+HH group.Dilated and congested blood vessels were seen in hippocampal tissue,conges-ted central veins were seen in hepatic tissue,and dilat-ed and congested liver sinusoids with mild granuloma-tous degeneration of hepatocytes were seen in rats of the SPS+HH group.Conclusion Hypobaric hypoxia exacerbates depression-like and anxiety-like behaviors in PTSD rats,as well as hematological indices and his-tomorphometric abnormalities in PTSD rats.

Vesicular glutamate transporter 2(VGlut2)is expressed in the PVN of the hypothalamic paraventricular nucleus(PVNVG1ut2)as an excitatory neurotransmitter,which regulates food intake and energy metabolism and plays an important role in maintaining homeostasis.However,it is not clear that the upstream and downstream projection network of PVNVGut2 neurons hinders the anal-ysis of glutamatergic neuron circuit function.Anterograde and retrograde tracer viruses were injec-ted into the PVN of VGlut2 mice by stereotactic brain injection technique to find the input and output nuclei of PVNVGlut2 neurons.Anterograde tracing results showed that PVNVGlut2 neurons pro-jected to the downstream medial amygdala(MeAD)and arcuate nucleus(ARC).Retrograde trac-ing results showed that PVNVGlut2 received input from the prefrontal nucleus(Pr),the reticular tegmental nucleus(RtTg),and the hypoglossal nucleus(12N).In addition,VGlut2 was found to be co-expressed with neuronal nitric oxide synthase(nNOS)neurons in the PVN.The anatomical net-work of PVNVG1ut2 neurons was analyzed by virus tracking tool,which laid the anatomical founda-tion for further study on the functional regulation of PVNVGlut2.

Objective:To analyze the correlation between body fat distribution measured by quantitative CT (QCT) and body mass index in adults receiving physical examination.Methods:It was a cross-sectional study. From January to December 2021, 3 205 adults undergoing physical examination who met the inclusion criteria and underwent chest CT and QCT examination in the health management discipline of Henan Provincial People′s Hospital were selected as the research objects. The general data were collected; and the subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate were measured by QCT. According to body mass index, the subjects were divided into normal group (18.5-<24.0 kg/m 2, 1 343 cases), overweight group (24.0-<28.0 kg/m 2, 1 427 cases) and obesity group (≥28.0 kg/m 2, 435 cases). One-way analysis of variance and χ2 test were used to compare the differences of QCT indexes among the three groups. Pearson and Spearman correlation analysis were used to evaluate the correlation between QCT indexes and body mass index. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic effect of QCT on obesity and fatty liver. Results:Subcutaneous fat area, visceral fat area, total abdominal fat area, liver fat content, abdominal obesity and fatty liver detection rate in obese group were all significantly higher than those in overweight group and normal group [males, (147.60±46.44) vs (104.33±27.68), (73.46±22.65) cm 2; (297.46±54.70) vs (229.40±53.12), (159.57±49.68) cm 2; (445.06±70.24) vs (333.73±62.91), (233.02±61.87) cm 2; 11.30% (7.90%, 15.55%) vs 8.75% (6.50%, 11.70%), 6.60% (4.80%, 8.70%); 100.0% vs 96.0%, 64.0%; 92.9% vs 86.7%, 73.3%; females, (213.96±48.61) vs (155.85±35.31), (107.24±31.01) cm 2; (185.41±43.88) vs (142.48±41.75), (96.56±36.50) cm 2; (399.37±68.07) vs (298.33±56.86), (203.80±57.53) cm 2; 9.80% (6.90%, 13.30%) vs 7.30% (5.05%, 9.80%), 5.40%(3.50%, 7.20%); 96.4% vs 74.8%, 28.9%; 87.3% vs 75.6%, 56.5%], and were all positively correlated with body mass index (males, r/ rs=0.709, 0.738, 0.831, 0.402, 0.464, 0.225; females, r/ rs=0.798, 0.695, 0.841, 0.416, 0.605, 0.276) (all P<0.001). In both male and female subjects, the detection rates of obesity based on QCT were significantly higher than those based on body mass index (male, 86.9% vs 16.6%; female, 49.3% vs 8.9%), and the detection rates of fatty liver based on QCT were significantly higher than those based on ultrasound (male, 83.6% vs 57.1%; female, 65.2% vs 27.6%) (all P<0.001). ROC curve showed that when the visceral fat area of 142 cm 2 was used as the cut-off value for the diagnosis of obesity in male subjects, the sensitivity and specificity was 100% and 15.8%, respectively; and when the cut-off value of liver fat content 5.0% was used to diagnose fatty liver, the sensitivity and specificity was 88.9% and 25.1%, respectively. When the visceral fat area of 115 cm 2 was set as the cut-off value for the diagnosis of obesity in female subjects, the sensitivity and specificity was 96.4% and 55.3%, respectively; when the liver fat content of 5.0% was set as the cut-off value for the diagnosis of fatty liver, the sensitivity and specificity was 83.7% and 43.2%, respectively. Conclusions:The indexes of abdominal fat and liver fat measured by QCT in adults receiving physical examination are all positively correlated with body mass index. The effect of QCT in the diagnosis of obesity and fatty liver are both better than body mass index and ultrasound.

Objective:To analyze the distribution of body fat with quantitative computed tomography (QCT) in people with normal body mass index (BMI).Methods:A cross-sectional study was conducted in the physical examination population who underwent chest CT and QCT examination in the Department of Health Management, Henan Provincial People′s Hospital from January to December in 2021, and 1 395 physical examination subjects who met the inclusion criteria were selected as the research subjects. The subjects were divided into five groups according to their age. The general data of the subjects were collected. The total abdominal fat area (TFA), visceral fat area (VFA), subcutaneous fat area (SFA), total abdominal muscle area (TMA) and muscle fat content (MFC) in the subjects were measured by QCT. One-way analysis of variance, Welch test and Kruskal-Wallis test were used to compare the above QCT measurement indexes between the two genders among different age groups with normal BMI. Pearson correlation analysis was used to analyze the correlation between VFA and sarcopenia indexes. Multivariate linear regression was used to analyze the relationship between VFA and linear correlation variables in the related indicators of sarcopenia.Results:There were significant differences in TFA, VFA, TMA and SMI among different age groups in subjects with normal BMI (all P<0.05). Pearson correlation analysis showed that VFA was negatively correlated with TMA in some age groups (male: 18-39 years group: r=-0.351; 40-49 years group: r=-0.278; 60-69 years group: r=-0.245; female:40-49 years group: r=-0.251; 50-59 years group: r=-0.270;≥70 years group: r=-0.391; all P<0.01); it was negatively correlated with SMI (male: 18-39 years group: r=-0.352; 40-49 years group: r=-0.340; 50-59 years group: r=-0.266; 60-69 years group: r=-0.316; female: 40-49 years group: r=-0.240; 50-59 years group: r=-0.284; all P<0.001); it was positively correlated with MFC (male: 18-39 years group: r=0.342; 40-49 years group: r=0.291; female: 50-59 years group: r=0.133; 60-69 years group: r=0.284; all P<0.05). Multivariate linear regression analysis showed that VFA was independently and negatively correlated with SMI in both men and women after adjusting for age interference factors (male B=-1.881, t=-6.025, P<0.001; female B=-0.603, t=-2.887, P=0.004), and it was independently positively correlated with MFC (male B=1.230, t=4.271, P<0.001;female B=0.893, t=3.836, P<0.001). There was an independent negative correlation between VFA and TMA in male subjects ( B=0.263, t=2.478, P=0.013). Conclusions:VFA is correlated with TMA, SMI and MFC in people with normal BMI. Regardless of gender, SMI has a negative effect on VFA, and MFC has a positive effect on VFA.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

Hepatic stellate cell(HSC)activation is a key link in the development of liver fibrosis.The metabolic reprogramming of activated HSC has become a hot topic in current research,especially the change of glycolysis is an important factor in regulating HSC activation.Based on the metabolic reprogramming in the process of HSC activation,this paper expounds the mechanism of regulating HSC activation and liver fibrosis through glycolysis,and reviews the research progress of traditional Chinese medicine and its active ingredients in regulating HSC glycolysis to prevent and treat liver fibrosis.Liver fibrosis is a complex pathological process involving multiple factors and pathways.From the perspective of regulating the glycolysis of activated HSC,it can provide a new idea for the development of anti-liver fibrosis drugs.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.