Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Central nervous system（CNS） disorders are characterized by complex pathological mechanisms and the presence of the blood-brain barrier（BBB）， which significantly limits the effectiveness of drug therapy. Traditional drug delivery modes include oral administration， intravenous injection and transdermal delivery， which have certain advantages， but it is difficult for the drugs to effectively cross the BBB. Therefore， it is crucial to find drug delivery modes that can efficiently traverse the BBB. Nasal drug delivery， as a non-invasive method， can realize the targeted delivery of drugs to the CNS via three pathways， including olfactory neurons， trigeminal neurons and blood circulation， and shows a broad application prospect in the treatment of CNS diseases. Numerous studies have further confirmed that nasal drug delivery combined with novel drug delivery systems such as lipid nanocarriers， nanoparticles， nanoemulsions and composite in situ gels can effectively load the active components of traditional Chinese medicine（TCM）， and significantly increase drug concentration in the brain， which provides new strategies for the treatment of CNS diseases. In this paper， the current status of drug delivery for CNS diseases was systematically sorted out， the characteristics of nasal drug delivery were discussed in depth， and the research progress of passive targeting， active targeting， and "guiding the meridian" drug delivery strategies for the nasal-to-brain transport of TCM active components was summarized and analyzed， which was aimed to provide references and insights for the development of drugs for CNS diseases and the application of TCM in nasal-to-brain delivery.

Herpes simplex viruses type 1(HSV1)is among the most ubiquitous human pathogens that cause a wide variety of disease states.The latent infection of the central nervous system and sporadically reactivation is the central part of HSV1 pathogenesis,which also brings challenges to antiviral therapies.At present,the mechanism of establishing,maintaining and reactivation of HSV1 has not been fully clarified,whereas it has been generally accepted that the epigenetic regulation may play an important role.Accumulating researches have also indicated that the lytic and latent viral genomes exhibit the different chromatin structures,and the accumulation of diverse post-translational modifies the histones endow viral genes with transcriptional activation or repression features.In addition,the latency-associate transcripts of virus may also participate in the genome epigenetic modification.In this review,we summarize the research progress of epigenetic regulation of HSV1 and highlight the critical role of chromatin remodeling in HSV1 lytic proliferation and establishment of latent infection.

The aim of this study was to explore the impact of chronic apical periodontitis(CAP)on atherosclerosis in apoE-/-mice fed high-fat diet(HFD).This investigation focused on the gut microbiota,metabolites,and intestinal barrier function to uncover potential links between oral health and cardiovascular disease(CVD).In this study,CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/-mice,as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining.16S rRNA sequencing revealed significant alterations in the gut microbiota,with harmful bacterial species thriving while beneficial species declining.Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis,leading to elevated levels of taurochenodeoxycholic acid(TCDCA),taurocholic acid(TCA),and tauroursodeoxycholic acid(TDCA).These metabolic shifts may contribute to atherosclerosis development.Furthermore,impaired intestinal barrier function,characterized by reduced mucin expression and disrupted tight junction proteins,was observed.The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions,highlighting the importance of the intestinal barrier in cardiovascular health.In conclusion,this research underscores the intricate interplay among oral health,gut microbiota composition,metabolite profiles,and CVD incidence.These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues,as well as the need for further investigations into the intricate mechanisms linking oral health,gut microbiota,and metabolic pathways in CVD development.

Objective To assess effect of ultrasound-guided erector spinae plane block(ESPB)combined with patient controlled intravenous analgesia(PCIA)on postoperative analgesia after cesarean section.Methods A total of 120 full-term singleton pregnant women who underwent cesarean section under spinal anesthesia at Jiaxing Maternal and Child Health Care Hospital from May 2022 to August 2023 were selected.Participants were randomly divided into three groups using a random number table:Group E(ESPB combined with PCIA),group T[transversus abdominis plane(TAP)block combined with PCIA],and control group(PCIA alone),with 40 women in each group.Visual analogue scale(VAS)and Bruggrmann comfort scale(BCS)scores during rest and coughing were recorded at 4h,8h,12h,24h,and 48h postoperatively.Number of effective PCIA presses,total sufentanil dosage,proportion of rescue analgesia and maternal satisfaction were also documented within 48h.Additionally,adverse reactions and neonatal outcomes were observed within the same 48h period.Results Postoperatively,VAS scores for rest and coughing in group E at 8h,12h,24h were significantly lower than those in group T,those in two groups were lower than those in control group(P＜0.05).Postoperatively at 8h,12h,and 24h,BCS scores in group E were significantly higher than those in group T,with both higher than those in control group(P＜0.05).Within 48h after surgery,the number of effective PCIA presses,proportion of rescue analgesia and total sufentanil dosage in group E were lower than those in group T,both lower than those in control(P＜0.05).Moreover,maternal satisfaction score in group E was significantly higher than that in group T,that in two groups was significantly higher than that in control group(P＜0.05).Within 48h after surgery,there were no significant differences in adverse reactions or neonatal outcomes among the three groups(P＞0.05).Conclusion Ultrasound-guided ESPB combined with PCIA outperforms TAP block combined with PCIA,with reducing analgesic dose and enhancing maternal satisfaction and comfort.

Objective　To analyze the causes of death of one case of imported falciparum malaria in Guangxi Zhuang Autonomous Region in January 2023, to provide a reference for the prevention of fatal malaria cases. Methods Interviews were conducted with the doctors who received and consulted the patient, as well as the family members of the patient. Clinical data from the patient's diagnosis and treatment process were collected, and the patient's clinical records and epidemiological investigation data were analyzed. Results The patient, Mr. He, a 53-year-old male from Pingnan County, Guigang City, Guangxi Zhuang Autonomous Region, returned from working in Côte d'Ivoire, Africa, and entered Guangxi on December 26, 2022. He returned home after his centralized quarantine was lifted on January 3, 2023. On January 4th, 2023, the patient developed dizziness and vomiting, considering himself to a possible COVID-19 infection, he did not seek treatment. On the morning of January 6, the patient developed a fever (peak body temperature of 40 ℃), accompanied by fatigue and sore throat, and the preemptive symptoms were aggravated. The patient was admitted to the Guancheng Town Health Center with "Pneumonia" and treated with ribavirin, dexamethasone, ceftriaxone sodium, etc. On January 7, the patient again experienced a high fever (40 ℃) and was discharged to the Emergency Department of the First Affiliated Hospital of Guangxi Medical University. Upon admission, the patient's blood pressure was measured at 78/53mmHg, further comprehensive examination showed a decrease in platelets and abnormalities in liver and renal function, procalcitonin levels at 49.9 ng/mL. Chest CT showed pneumonia, and fluid supplements and antibiotics were given. On January 8, malaria parasites were found in the patient's blood smear, and the patient was diagnosed with malaria (not classified, confirmed as falciparum malaria on January 9th). The patient was recommended to transfer to the provincial malaria-designated hospital, but his family refused. On January 8 at 13:27, the patient excreted approximately 700 g of dark red bloody stools accompanied by blurred consciousness and received hemostasis treatment. After coordinating with multiple parties, four doses of "artemisinin injection " (60 mg/dose) were taken for treatment. At 18:59 on January 8, intravenous administration of 60 mg injectable Artesunate was given, accompanied by symptomatic treatment for fever reduction and rehydration. At 19:40, the patient developed severe hypoglycemia, and severe metabolic acidosis, and blood pressure continued to decrease despite the use of vasopressors. After comprehensive treatment at 3:00 am on January 9, the patient's condition continued to deteriorate, the patient's shock could not be corrected, he lapsed into a coma, and the family requested to be discharged from the hospital. The patient returned home at 7:00 am and died of multiple organ failure at 7:30 am. Conclusions For imported malaria, early and precise diagnosis based on epidemiological history, clinical symptoms, laboratory test results, early antimalarial treatment, and management of organ dysfunction are the keys to avoiding fatal outcomes.

Objective:To investigate the appetite of patients with lymphoma during chemotherapy and its influencing factors.Methods:A total of 103 patients with lymphoma who underwent chemotherapy were sequentially selected in Fujian Medical University Union Hospital from December 2020 to August 2021. The questionnaire survey was carried out by using general information and Karnofsky score was performed. Appetite score was calculated according to Chinese version of the appetite symptom questionnaire for cancer patients. Multiple linear regression analysis was used to analyze the influencing factors of appetite status of lymphoma patients during chemotherapy, and Pearson correlation analysis was used to explore the relationship between Karnofsky score and appetite score of patients.Results:For patients with lymphoma during chemotherapy, Karnofsky score was (75±18) scores and the appetite score was (25.0±5.0) scores. Univariate analysis showed that age, body mass index (BMI), nausea and vomiting, oral mucosa rupture, gum infection, fever, throat infection were influencing factors of appetite score of patients (all P < 0.05). Multivariate analysis showed that patients ' age ( B = -1.118, β = -0.187, P = 0.016), BMI ( B = -2.047, β = -0.271, P = 0.001), nausea and vomiting ( B = -4.352, β = -0.411, P < 0.001) were the independent influencing factors of appetite score. Correlation analysis showed that the Karnofsky score was positively correlated with appetite score ( r = 0.361, P < 0.05). Conclusions:Special attention should be paid to the appetite of elder lymphoma patients with lower BMI during chemotherapy, and nausea and vomiting should be paid more attention; targeted measures of increasing the patients' appetite could improve their nutritional level and prognosis.

Objective:To investigate the application value of establishing the differential diagnosis model of pulmonary tuberculosis using routine laboratory data.Methods:The retrospective study was conducted. The routine laboratory data of newly diagnosed patients with pulmonary tuberculosis and other pulmonary diseases in Beijng Jishuitan Hospital and Beijing Hepingli Hospital from May 2015 to November 2021were collected. According to the random numbers showed in the computer, all the 11516 patients were divided into training dataset and test dataset with a ratio of 9∶1. Four machine learning algorithms, Support Vector Machine, Random Forest, K-Nearest Neighbor and Logistic Regression, were used to build models and select features. The diagnostic accuracy of each model was verified by using the 10-fold cross-validation method and the performance of each model was evaluated by using the receptor operator of characteristic (ROC) curve.Results:Random Forest was selected as the optimal machine learning algorithm to build the best feature model in the study. According to importance scale of factors, the differential diagnosis model of pulmonary tuberculosis consisting of 37 non-specific test indexes. In the validation set and test set the accuracy and area under curve (AUC) of the models were 0.747 and 0.736, the sensitivity, specificity and accuracy were 68.03% and 68.75%, 70.91% and 67.90%, 70.30% and 68.12%, respectively.Conclusion:A key tool in the differential diagnosis model of pulmonary tuberculosis was established by routine laboratory data in combination with machine learning. The results of this study need to be further verified by more data from medical institutions.

Objective To rapidly explore the chemical components of Xiaotan Tongfu formula, and to provide scientific basis for the basic research and clinical treatment of the formula. Methods Analysis was performed on an Agilent 1290 ultra-performance liquid chromatography system coupled with an Agilent 6530 accurate quality Q-TOF/MS system, by using a Waters ACQUITY UPLC BEH C₁₈ column (2.1 mm × 100 mm, 1.7 μm), with a gradient elution applying 0.1% aqueous formic acid solution and acetonitrile as a mobile phase. The flow rate was 0.3 ml/min. The column temperature was 30°C. The injection volume was 1 μl, and the detection wavelength was 254 nm. Mass spectrometry (MS) data were collected in both positive and negative ESI ion modes. Components in the formula were identified by using the in-house compound database, and comparing the retention time (tR), MS1 and MS2 data with the standard compounds, and the online compound MS database. Results A total of 55 compounds were identified from Coptis coptidis, Pseudomonas solani, Rhubarb, Araceae artemisiae and Pinellia chinensis. Conclusion The established UHPLC-Q-TOF/MS method could systematically and accurately identify the chemical components from Xiaotan Tongfu formula, and provided a reference for the quality marker selection and the research on the active ingredient.

OBJECTIVE：To investigate the effect of increasing efficacy and decreasing toxicity of Limax extract （LE）on cyclophosphamide（CTX）in the treatment of hepatocellular carcinoma. METHODS ：The mice were randomly divided into normal group，model group ，CTX group （0.02 g/kg），LE low-dose ，medium-dose and high-dose groups （LEL，LEM，LEH group ，0.6，1.2，2.4 g/kg），CTX+LE low-dose ，medium-dose and high-dose combination groups （CTX+LEL，CTX+LEM，CTX+ LEH group ，the same dose as single drug group ），with 10 huangrenbin518@163.com mice in each group. Except for normal group ，other groups were inoculated with hepatoma cells H 22 in the left ar mpit to establish tumor bearing models. After 24 h of inoculation ，normal group and model group were intragastrically given normal saline ， and administration groups were intragastrically given corresponding drugs ，once a day ，for 10 days. On the second day after the last administration ，the general conditions of mice in each group were observed ；the body mass ，thymus index （LI），spleen index （SI）were measured ；the tumor inhibition rate was detected. The effect （q）of combination therapy was evaluated by King ’s formula . The counts of WBC ，RBC and PLT ，serum contents of ALT ，ALT，Scr and BUN were detected in model group ，CTX group and combination groups ，and the contents of MDA，SOD and GSH ，the levels of VEGF ，TNF-α and IL-6 in the tumor tissue were detected by colorimetry and ELISA in above groups. The protein expression of oncogenes （p53，Bcl-2 and Bax ）were detected by immunohistochemical method in model group，CTX group and CTX+LEM group. RESULTS ：The mice in the model group were in poor spirit and had symptoms of excessive drinking and eating ；although the body weight ，TI and SI were not significantly abnormal compared with normal group （P＞0.05），WBC count and AST content were significantly increased ，ALT and BUN contents were significantly decreased （P＜ 0.05 or P＜0.01）. Compared with model group ，above symptoms of mice were all improved in administration groups. The tumor weight of administration groups ，TI and SI of CTX group and TI of combination groups were decreased significantly ，but tumor weight of LEL group and LEH group ，TI and SI of LE single groups and combination groups were significantly higher than CTX group；tumor weight of combination groups were significantly lower than CTX group （P＜0.05 or P＜0.01）. The tumor inhibition rates of administration groups were 29.58％-72.08％. The q values of CTX+LEL group ，CTX+LEM group and CTX+LEH group were 1.03，0.97 and 0.86，respectively. Compared with model group ，WBC count ，AST and BUN contents of CTX group ，MDA contents of combination groups ，VEGF，TNF-α and IL-6 levels of administration groups ，the protein expression of Bcl- 2 in CTX group and CTX+LEM group were decreased significantly ；the activities of SOD and GSH of administration groups ，the protein expression of p 53 in CTX+LEM group and Bax in CTX group ，CTX+LEM group were increased significantly （P＜0.05 or P＜ 0.01）；WBC counts and AST contents of administration groups ，ALT content of CTX+LEM group ，SOD activity of CTX+LEH group and GSH activity of CTX+LEM group were all significantly higher than those of CTX group ；MDA content of CTX+LEH group，VEGF and TNF-α levels of CTX+LEM group and CTX+LEH group，IL-6 levels of administration groups were all significantly lower than CTX group （P＜0.05 or P＜0.01）. CONCLUSIONS ：LE combined with CTX can increase the anti-tumor effect，and LE can reduce the toxicity of CTX induced immunosuppression and bone marrow suppression in mice ，with effect of increasing efficacy and decreasing toxicity. The effect may be related to antioxidant stress ，inhibition of angiogenesis and secretion of inflammatory factors ，and regulation of apoptosis protein expression.