ObjectiveTo investigate the mechanisms by which Renshentang treats atherosclerosis （AS） in mice， focusing on the regulation of endothelial inflammatory responses mediated by transient receptor potential vanilloid subtype 1 （TRPV1）. MethodsAn AS model was established in apolipoprotein E knockout （ApoE^-/-） mice fed a high-fat diet. The mice were randomly divided into a simvastatin group （0.02 g·kg^-1·d^-1） and low-， medium-， and high-dose Renshentang groups （1.77， 3.54， 7.08 g·kg^-1·d^-1）， with 12 mice in each group. ApoE^-/- mice were fed a high-fat diet and treated simultaneously. C57BL/6J mice fed a normal diet served as the normal group （n=9）. After continuous administration for 12 weeks， mice were anesthetized and the aortas were collected. Oil Red O staining was used to observe lipid plaque formation in the aorta. Hematoxylin-eosin （HE） staining was performed to examine pathological changes in the aortic root. Immunohistochemistry was used to analyze the levels of pro-inflammatory factors tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， as well as the expression of TRPV1， phosphorylated phosphoinositide 3-kinase （p-PI3K）， and phosphorylated protein kinase B （p-Akt） in the aortic root. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect endothelial nitric oxide synthase （eNOS） mRNA expression in the aorta， and Western blot was used to detect TRPV1 protein expression. ResultsCompared with the normal group， the model group showed a significant increase in aortic plaque formation （P<0.01） and significantly elevated levels of TNF-α and IL-1β in the aortic root （P<0.01）. The expression levels of TRPV1， p-PI3K， and p-Akt were decreased （P<0.05， P<0.01）， and eNOS mRNA expression was reduced （P<0.05， P<0.01）. Compared with the model group， all Renshentang groups significantly reduced aortic plaque formation （P<0.01）， significantly decreased TNF-α and IL-1β levels （P<0.01）， and markedly increased the expression levels of TRPV1， p-PI3K， p-Akt， and eNOS mRNA （P<0.05， P<0.01）. ConclusionRenshentang may inhibit endothelial inflammation and suppress the formation of AS by increasing TRPV1 protein expression and up-regulating the PI3K/Akt/eNOS signaling pathway， which may be one of the molecular mechanisms underlying its therapeutic effect against AS.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment"， clinical presentations often involve a complex mixture of deficiency and excess， as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing"， advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals， treatment should focus on dispersing and unblocking through modified Gegen Decoction （葛根汤）. For wind-dampness binding， it is recommended to unblock and drain， using modified Qingshang Juantong Decoction （清上蠲痛汤）. For damp-heat congestion， unblocking and clearing is the method， using modified Toufeng Shen Formula （头风神方）. For liver-gallbladder qi constraint， unblocking and soothing is the treatment principle， and modified Sanpian Decoction （散偏汤） is suggested. For insufficiency of center qi， even supplementation method is recommended， and modified Yiqi Congming Decoction （益气聪明汤） can be used. For liver yang hyperactivity， unblocking and subduing are combined， using modified Xunlong Decoction （驯龙汤）. For deficiency-cold in the liver and stomach， warming， harmonizing， unblocking， and descending are applied， using modified Wuzhuyu Decoction （吴茱萸汤）. For blood deficiency with cold congelation， unblocking and nourishing are undertaken together， using modified Danggui Sini Decoction （当归四逆汤）. The ultimate goal is to restore the dynamic balance of yin， yang， qi， and blood in the body， thereby allevia-ting pain by restoring clarity and function to the head orifices.

This paper summarizes professor WANG Qingguo's experience in treatment of headache based on the "achieving harmony by unblocking and balancing" concept. It is considered that although the pathogenesis of headache is generally attributed to "pain arises from obstruction" and "pain arises from malnourishment"， clinical presentations often involve a complex mixture of deficiency and excess， as well as cold and heat patterns. Professor WANG proposes the diagnostic and therapeutic theory of "achieving harmony by unblocking and balancing"， advocating for equal emphasis on "freeing the flow of qi and blood" and "regulating the balance of yin and yang". He has summarized eight treatment methods for common headache patterns. For wind-cold attacking the collaterals， treatment should focus on dispersing and unblocking through modified Gegen Decoction （葛根汤）. For wind-dampness binding， it is recommended to unblock and drain， using modified Qingshang Juantong Decoction （清上蠲痛汤）. For damp-heat congestion， unblocking and clearing is the method， using modified Toufeng Shen Formula （头风神方）. For liver-gallbladder qi constraint， unblocking and soothing is the treatment principle， and modified Sanpian Decoction （散偏汤） is suggested. For insufficiency of center qi， even supplementation method is recommended， and modified Yiqi Congming Decoction （益气聪明汤） can be used. For liver yang hyperactivity， unblocking and subduing are combined， using modified Xunlong Decoction （驯龙汤）. For deficiency-cold in the liver and stomach， warming， harmonizing， unblocking， and descending are applied， using modified Wuzhuyu Decoction （吴茱萸汤）. For blood deficiency with cold congelation， unblocking and nourishing are undertaken together， using modified Danggui Sini Decoction （当归四逆汤）. The ultimate goal is to restore the dynamic balance of yin， yang， qi， and blood in the body， thereby allevia-ting pain by restoring clarity and function to the head orifices.

Objective To analyze the factors affecting the prognosis of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) undergoing immunotherapy and construct an individualized prognostic nomogram prediction model. Methods A retrospective analysis was conducted on the clinical data of 385 patients with driver gene-negative, locally advanced or metastatic NSCLC who received first-line immune checkpoint inhibitors. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors, and a prognostic nomogram model was established. The predictive performance of the model was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves and area under the curve (AUC), and calibration curves. The cutoff value of the nomogram was calculated to stratify patients by risk. Survival curves were calculated by Kaplan-Meier analysis. Results Age (HR=1.775, 95%CI: 1.265-2.490), degree of differentiation (HR=0.365, 95%CI: 0.257-0.519), low PD-L1 expression (HR=0.661, 95%CI: 0.455-0.960), high PD-L1 expression (HR=0.423, 95%CI: 0.297-0.603), SCC-Ag (HR=1.549, 95%CI: 1.109-2.163), and CONUT score (HR=2.527, 95%CI: 1.797-3.554) were independent risk factors affecting overall survival (OS) of patients with NSCLC undergoing immunotherapy. The nomogram prediction model constructed on the basis of these factors had a C-index of 0.767. Time-dependent ROC curves for survival showed that the AUCs for 1-, 2-, and 3-year OS were 0.830, 0.853, and 0.886, respectively. Calibration curves indicated that the nomogram-predicted survival rates were in good agreement with the actual outcomes. The cutoff value for the study’s nomogram prediction model was 136.60 points, and survival curves showed statistically significant differences between different risk groups (P<0.05). Conclusion The nomogram model established in this study can effectively predict the prognosis of patients with driver gene-negative locally advanced or metastatic NSCLC treated with first-line immunosuppressive therapy. It provides a new tool for assessing prognosis and aids clinicians in formulating individualized treatment plans.

ObjectiveTo analyze trends in the incidence and mortality of pancreatic cancer among the registered residents in Jinhua City of Zhejiang Province from 2016 to 2024, and to predict incidence and mortality rates from 2025 to 2027, thereby providing a reference for refining prevention and control strategies. MethodsData on pancreatic cancer incidence and mortality among the registered residents in Jinhua City from 2016 to 2024 were collected. The Joinpoint regression model was used to calculate the average annual percentage change (AAPC) to analyze the temporal trends of pancreatic cancer incidence and mortality. Furthermore, a GM (1,1) model was constructed using Excel 2019 to predict incidence rates and mortality rates for the years 2025 to 2027. ResultsFrom 2016 to 2024, the crude incidence and crude mortality rates of pancreatic cancer among the registered residents in Jinhua City were 8.41/100 000 and 8.19/100 000, respectively, both showing upward trends (AAPC=3.55%, 95%CI: 1.69%-5.63%; AAPC=3.35%, 95%CI: 1.08%-5.93%), while the standardized incidence and mortality rates were 5.21/100 000 and 4.93/100 000, respectively, with no statistically significant trends (AAPC=1.12% and 0.52%, both P>0.05). The incidence and mortality rates of pancreatic cancer were higher in men than in women. Both crude incidence and crude mortality rates rose steadily with increased age (both P<0.01). According to the GM (1,1) model, the crude mortality rate of pancreatic cancer among the registered residents in Jinhua City is projected to continue its upward trend from 2025 to 2027 (9.37/100 000, 9.60/100 000, and 9.83/100 000, respectively). ConclusionFrom 2016 to 2024, both the crude incidence and crude mortality rates of pancreatic cancer among registered residents in Jinhua City showed continuous upward trends, and the crude mortality rate is likely to continue rising from 2025 to 2027. Efforts to prevent and control pancreatic cancer should be strengthened, particularly among men and the very elderly.

With the aging of the population and the increasing number of patients with thromboembolic diseases, oral anticoagulants are more and more widely used. Anticoagulant-related nephropathy (ARN) is a significant adverse reaction in the treatment with oral anticoagulants, generally considered to be a form of acute kidney injury caused by excessive anticoagulation. The mechanisms involved may include glomerular hemorrhage, obstruction of renal tubules by red cell casts, and damage to tubular epithelial cells. Abnormalities in coagulation function and renal function are the main risk factors for ARN; older age, diabetes mellitus, and cardiovascular diseases such as hypertension and heart failure also increase the risk of ARN occurrence. ARN should be managed based on individual patient characteristics. Benefits and risks of treatment should be carefully considered when choosing oral anticoagulants; renal function should be closely monitored during treatments to detect potential risks early. In case of ARN, it is advised to promptly adjust the anticoagulant therapy and provide symptomatic supportive treatments. In severe cases, treatments with methylprednisolone combined with hemodialysis can be employed.

Objective:To investigate the characteristics of resting-state mirror homotopic connectivity and the gray matter volume of brain in patients with neuropsychiatric systemic lupus erythematosus (NPSLE).Methods:From June 2020 to March 2023, a total of 35 NPSLE patients (NPSLE group) and 30 non-NPSLE patients (non-NPSLE group) were selected from Taizhou People's Hospital Affiliated to Nanjing Medical University, another 31 healthy volunteers were recruited as the healthy controls(HC group). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and mini-mental state examination (MMSE) assessments. The patients in NPSLE and non-NPSLE groups were additionally assessed using the fatigue scale for motor and cognitive functions (FSMC) and the hospital anxiety and depression scale (HADS).The DPABI V7.0 toolkit based on the MATLAB platform was used to preprocess the rs-fMRI data and calculate the voxel-mirrored homotopic connectivity(VMHC) indexes, and the differences in VMHC between groups were evaluated by covariance analysis in SPM12.0 software, and the VMHC values of brain regions with significant differences were extracted for further comparison between the two groups.Partial correlation analysis was performed to investigate the association between VMHC values and clinical parameters in NPSLE patients.The brain regions with significant differences between NPSLE patients and non-NPSLE patients were used as region of interest (ROI), and gray matter volumes within these ROIs were then calculated by VBM8 toolbox.Results:(1)There were statistically significant differences in the VMHC values of bilateral precentral gyrus, bilateral dorsolateral superior frontal gyrus, bilateral medial and paracingulate gyrus, bilateral parahippocampal gyrus, bilateral middle occipital gyrus, bilateral postcentral gyrus, and bilateral superior temporal gyrus among the 3 groups( F=11.246-14.102, all P<0.05). The NPSLE group exhibited significantly lower VMHC values in these regions compared to both the non-NPSLE group and HC group (all P<0.05), but there were no significant differences in these regions between the non-NPSLE group and HC group (all P>0.05).(2) The gray matter volumes of bilateral dorsolateral superior frontal gyrus(right: (0.57±0.11)mm 3, (0.65±0.08)mm 3, t=-3.409, P=0.001; left: (0.53±0.10)mm 3, (0.60±0.07)mm 3, t=-3.082, P=0.003), bilateral precentral gyrus(right: (0.32±0.06)mm 3, (0.35±0.04)mm 3, t=-2.044, P=0.045; left: (0.39±0.06)mm 3, (0.42±0.04)mm 3, t=-2.505, P=0.015), right medial and paracingulate gyrus((0.66±0.08)mm 3, (0.70±0.07)mm 3, t=-2.491, P=0.015) and left superior temporal gyrus((0.57±0.09)mm 3, (0.61±0.06)mm 3, t=- 2.344, P=0.022) in the NPSLE group were smaller than those of non-NPSLE group.(3)Correlation analysis showed that the VMHC value of dorsolateral superior frontal gyrus was positively correlated with IgA level in NPSLE patients ( r=0.353, P=0.047). Conclusion:Patients with NPSLE generally have decreased mirror homotopy functional connectivity in the cerebral hemispheres, accompanied by a decrease in gray matter volume in some brain regions, which can provide a certain neuroimaging basis for the pathogenesis of brain injury.

Intraluminal thrombus(ILT)at the vertebral artery origin is rare and often missed due to atypical symptoms.However,it poses a high risk of artery-to-artery embolism and severe posterior circulation ischemia.This article reports a case of missed diagnosis of ILT to improve the diagnostic ability.The patient,a 49-year-old male was admitted to emergency department with sudden dizziness accompanied by nausea for 12 hours.Head CT suggested posterior circulation ischemia.Patient was given aspirin 0.2 g/d and atorvastatin 20 mg/d orally and discharged from the hospital.Head MRI in the outpatient department showed a recent infarct in the right cerebellar hemisphere next day.On the 28th,dizziness recurred,accompanied by unsteady walking and right-sided hemisensory numbness.The symptoms persisted and did not improve.He was admitted to the hospital on the 29th.Cervical CTA showed severe stenosis at the origin of the right vertebral artery,filling defect in the distal lumen combined with the Donut sign.Thus,ILT was diagnosed.The drug treatment regimen was adjusted to aspirin 100 mg/d combined with clopidogrel 75 mg/d for a total of 15 weeks.High-resolution MRI of the cervical blood vessels in the outpatient department showed occlusion of the V1-V2 segment of the right vertebral artery.On November 2,endovascular treatment was performed under local anesthesia.At 90 days and 6 months of follow-up after the operation,no recurrence of cerebral ischemia events occurred,and the mRS score was 0.This case highlights the need for vigilance toward ILT in posterior circulation ischemia when initial imaging is inconclusive.Early dynamic CTA(5-7 days)combined with dual antiplatelets may prevent thrombus progression and improve outcomes.