Objective:Locus coeruleus(LC)noradrenergic(NEergic)neurons densely project to anterior piriform cortex(aPC).However,the modulation of LC to aPC remains unclear.Therefore,this study aims to investigate the effect of LC-aPC projection on the modulation of aPC in odor perception.Methods:The AAV-DIO-ChR2-eYFP virus was injected into LC of DBH-Cre mice and the optrode was placed into aPC.Optogenetics combined with in vivo electro-physiology were used to record the air/odor-evoked response of aPC pyramidal neurons.Results:The immunofluores-cent staining showed that the LC project directly to aPC.Activation of aPC NEergic fibers decreased the spontaneous re-sponses and odor-evoked responses of aPC pyramidal neurons.Conclusion:Activation of aPC NEergic neurons inhibits the spontaneous responses and odor-evoked responses of aPC pyramidal neurons.

Objective:Locus coeruleus(LC)noradrenergic(NEergic)neurons densely project to anterior piriform cortex(aPC).However,the modulation of LC to aPC remains unclear.Therefore,this study aims to investigate the effect of LC-aPC projection on the modulation of aPC in odor perception.Methods:The AAV-DIO-ChR2-eYFP virus was injected into LC of DBH-Cre mice and the optrode was placed into aPC.Optogenetics combined with in vivo electro-physiology were used to record the air/odor-evoked response of aPC pyramidal neurons.Results:The immunofluores-cent staining showed that the LC project directly to aPC.Activation of aPC NEergic fibers decreased the spontaneous re-sponses and odor-evoked responses of aPC pyramidal neurons.Conclusion:Activation of aPC NEergic neurons inhibits the spontaneous responses and odor-evoked responses of aPC pyramidal neurons.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

This article summarized clinical experience in differentiating and treating non-obstructive hypertrophic cardiomyopathy （HCM） based on the concept of nourishing the heart and softening the hardness. It is considered that HCM belongs to the category of "heart accumulation"， with the fundamental cause being depletion of the spleen and kidney， and phlegm-stasis accumulation， as well as qi-yin exhaustion， serving as the manifestations. Spleen and kidney depletion leads to the transformation of phlegm and stasis， which accumulate in the heart； over time， this phlegm-stasis accumulation consumes heart qi and yin， resulting in the heart being deprived of nourishment， which eventually leads to the damage to both the function and structure of heart. Therefore， the method of nourishing the heart and softening the hardness is proposed for the treatment of non-obstructive HCM. Emphasis is placed on softening hardness and dissipating masses throughout the entire treatment process， often using Modified Siwei Ruanjian Formula （四味软坚方加减）. During periods with prominent symptoms， the main treatment is boosting qi and nourishing yin to soften hardness and dissipate masses with self-made Yuxin Ruanjian Formula （自拟育心软坚方） in modifications； in stable periods， the main treatment is boosting kidney and fortifying spleen to soften hardness and dissipate masses with self-made Pishen Tongzhi Formula （脾肾同治方） in modifications.

Background: Intradermal microdroplet injections of botulinum toxin type-A (BoNT/A) effectively ameliorate rosacea-related angiogenesis, but the mechanism remains unclear. Objective: To explore the anti-angiogenesis of BoNT/A in the rosacea-like mouse model and to measure the secretion of vascular endothelial growth factor (VEGF) by mast cells. Methods: A rosacea-like mouse model was induced by LL37 in both Mas-related G-proteincoupled receptor B2 conditional knockout (MrgprB2 −/− ) mice and wild-type (WT) mice, then treated with BoNT/A and/or Apatinib. The abundance of endothelial cells and mast cells in mouse skin was determined using dual immunofluorescence staining. The VEGF levels in supernatants and cell lysates of laboratory of allergic disease 2 (LAD2) mast cells were assessed using reverse transcription quantitative polymerase chain reaction, western blots, and enzyme-linked immunosorbent assay. The effect of conditioned medium (CM) collected from LAD2 on human umbilical vein endothelial cells (HUVECs) was determined using tube formation assays. The number of proliferative cells was confirmed using the 5-ethynyl-2’-deoxyuridine incorporation assays.The effect of BoNT/A on the internalization of Mas-related G-protein-coupled receptor X2 (MRGPRX2) was detected using flow cytometry and immunofluorescence staining. Results: LL37-induced rosacea-like skin manifestations were significantly alleviated in MrgprB2 −/− mice compared to WT controls. BoNT/A mitigated the LL37-induced secretion of VEGF by LAD2. The CM from BoNT/A-treated LAD2 inhibited HUVEC proliferation and tube formation. The LAD2 cells co-treated with LL37 and BoNT/A exhibited dramatically enhanced MRGPRX2 internalization. Conclusion BoNT/A enhances LL37-mediated MRGPRX2 internalization in mast cells, thereby reducing VEGF secretion and neovascularization and improving facial flushing symptom in rosacea.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objectives:To evaluate the predictive value of Tabular Prior-data Fitted Network(TabPFN) for short-term outcome in patients with spontaneous intracerebral hemorrhage (sICH), and compared with the Extreme Gradient Boosting (XGboost) model and traditional logistic regression (LR) model. Methods:Patients with sICH admitted to the Department of Neurology, Hefei Second People's Hospital from January 2018 to March 2024 were included retrospectively. The demographic and baseline data were collected. At 3 months after onset, the modified Rankin Scale score was used to determine the outcome, 0-2 was defined as good outcome and >2 was defined as poor outcome. All enrolled patients were randomly divided into a training set and a testing set at a ratio of 7:3. Feature selection was performed using recursive feature elimination (RFE) method, and then the selected feature variables were included into TabPFN, XGboost, and LR models for training and testing. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the models. Shapley additive explanations (SHAP) method was used for model interpretation.Results:A total of 547 patients with sICH were enrolled, including 367 males (67.1%), with a median age of 65 (interquartile range, 54-76) years. Two hundred twenty-six patients (41.3%) had poor outcome. Age, baseline blood pressure (systolic blood pressure, diastolic blood pressure), baseline laboratory tests (white blood cell count, red blood cell count, platelet count, neutrophil count, hemoglobin, fasting blood glucose, creatinine, uric acid, urea nitrogen, alanine aminotransferase, aspartate aminotransferase), hematoma rupture into the ventricle, island sign, baseline hematoma volume, and baseline National Institutes of Health Stroke Scale (NIHSS) score were selected as characteristic variables using RFE method. ROC curve analysis showed that the ROC AUC for TabPFN, Xgboost, and LR models predicting poor short-term outcome in the testing set were 0.918 (95% confidence interval [ CI] 0.870-0.966], 0.883 (95% CI 0.826-0.940), and 0.905 (95% CI 0.854-0.957), respectively. SHAP analysis showed that the top four important variables in the TabPFN model were baseline NIHSS score, baseline hematoma volume, baseline aspartate aminotransferase, and age. Conclusions:The TabPFN model is superior to the LR model and the XGBoost model in predicting poor outcome in patients with sICH. In the TabPFN model, baseline NIHSS score, baseline hematoma volume, aspartate aminotransferase, and age are the most important predictors of poor outcome in patients with sICH.Objectives To evaluate the predictive value of Tabular Prior-data Fitted Network(TabPFN) for short-term outcome in patients with spontaneous intracerebral hemorrhage (sICH), and compared with the Extreme Gradient Boosting (XGboost) model and traditional logistic regression (LR) model. Methods Patients with sICH admitted to the Department of Neurology, Hefei Second People's Hospital from January 2018 to March 2024 were included retrospectively. The demographic and baseline data were collected. At 3 months after onset, the modified Rankin Scale score was used to determine the outcome, 0-2 was defined as good outcome and >2 was defined as poor outcome. All enrolled patients were randomly divided into a training set and a testing set at a ratio of 7:3. Feature selection was performed using recursive feature elimination (RFE) method, and then the selected feature variables were included into TabPFN, XGboost, and LR models for training and testing. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the models. Shapley additive explanations (SHAP) method was used for model interpretation. Results A total of 547 patients with sICH were enrolled, including 367 males (67.1%), with a median age of 65 (interquartile range, 54-76) years. Two hundred twenty-six patients (41.3%) had poor outcome. Age, baseline blood pressure (systolic blood pressure, diastolic blood pressure), baseline laboratory tests (white blood cell count, red blood cell count, platelet count, neutrophil count, hemoglobin, fasting blood glucose, creatinine, uric acid, urea nitrogen, alanine aminotransferase, aspartate aminotransferase), hematoma rupture into the ventricle, island sign, baseline hematoma volume, and baseline National Institutes of Health Stroke Scale (NIHSS) score were selected as characteristic variables using RFE method. ROC curve analysis showed that the ROC AUC for TabPFN, Xgboost, and LR models predicting poor short-term outcome in the testing set were 0.918 (95% confidence interval [ CI] 0.870-0.966], 0.883 (95% CI 0.826-0.940), and 0.905 (95% CI 0.854-0.957), respectively. SHAP analysis showed that the top four important variables in the TabPFN model were baseline NIHSS score, baseline hematoma volume, baseline aspartate aminotransferase, and age. Conclusions The TabPFN model is superior to the LR model and the XGBoost model in predicting poor outcome in patients with sICH. In the TabPFN model, baseline NIHSS score, baseline hematoma volume, aspartate aminotransferase, and age are the most important predictors of poor outcome in patients with sICH.

Objective:This study aims to investigate the effects on the behavior of mice by optogenetic activation the neural projections from the central amygdala(CeA)to the dorsal raphe nucleus(DRN).Methods:AAV-hSyn-eYFP virus was injected into CeA of C57BL/6J mice,and the projections from CeA to DRN were observed by immunofluores-cent staining.The AAV-hSyn-ChR2-mCherry virus was injected into CeA,and AAV-DIO-eYFP was injected into DRN in Ser-Cre mouse to specifically label the serotonergic neurons.Patch-clamp recording combined with optogenetic tech-nology were employed to record the light-evoked inward currents of DRN serotonergic neurons.AAV-hSyn-ChR2-mCher-ry virus was injected into CeA and optical fiber was implanted into DRN,and the effects of optogenetic activation of the CeA-DRN neural circuit on the locomotor ability of mice was studied by open field test.Results:Four weeks after injec-tion of AAV-hSyn-eYFP virus into CeA of C57BL/6J mice,axon terminals from CeA eYFP-cells were observed in the DRN.Activation of the neural projections from the CeA to the DRN induced inhibitory inward currents in DRN seroton-ergic neurons.Activation of the projections from CeA to DRN circuit decreased the total distance and the time of the center of the open field in mice,and increased the immobility time of mice.Conclusion:The CeA neurons directly pro-ject to the DRN.Activation of CeA-DRN circuit exerts an inhibitory regulatory effect on DRN serotonergic neurons and reduces the locomotor ability of mice.

Objective:This study aims to investigate the effects on the behavior of mice by optogenetic activation the neural projections from the central amygdala(CeA)to the dorsal raphe nucleus(DRN).Methods:AAV-hSyn-eYFP virus was injected into CeA of C57BL/6J mice,and the projections from CeA to DRN were observed by immunofluores-cent staining.The AAV-hSyn-ChR2-mCherry virus was injected into CeA,and AAV-DIO-eYFP was injected into DRN in Ser-Cre mouse to specifically label the serotonergic neurons.Patch-clamp recording combined with optogenetic tech-nology were employed to record the light-evoked inward currents of DRN serotonergic neurons.AAV-hSyn-ChR2-mCher-ry virus was injected into CeA and optical fiber was implanted into DRN,and the effects of optogenetic activation of the CeA-DRN neural circuit on the locomotor ability of mice was studied by open field test.Results:Four weeks after injec-tion of AAV-hSyn-eYFP virus into CeA of C57BL/6J mice,axon terminals from CeA eYFP-cells were observed in the DRN.Activation of the neural projections from the CeA to the DRN induced inhibitory inward currents in DRN seroton-ergic neurons.Activation of the projections from CeA to DRN circuit decreased the total distance and the time of the center of the open field in mice,and increased the immobility time of mice.Conclusion:The CeA neurons directly pro-ject to the DRN.Activation of CeA-DRN circuit exerts an inhibitory regulatory effect on DRN serotonergic neurons and reduces the locomotor ability of mice.

In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance， Innovation， and Development of traditional Chinese medicine（TCM） and the spirit of the National Conference on TCM， Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis （AR） and they reached a basic consensus. In recent years， the prevalence of AR has been on the rise， threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity， and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease， western medicine features rapid onset. However， it is cost-intensive and causes severe surgical trauma， and the recurrence is common. TCM boasts diverse methods for AR， which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion， runny nose， or dysosmia in the attack stage， preventing recurrence in the remission stage， and treating refractory AR or steroid-resistant AR. In particular， acupuncture enjoys a reputation in treatment of AR， which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR， TCM regulates the psychosomatic conditions， which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine， give full play to the unique nonnegligible and irreplaceable advantages of TCM， formulate a comprehensive diagnosis and treatment scheme for learning and promotion， and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.