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.

Objective:To investigate the current status of research in gene therapy for retinitis pigmentosa (RP) from 2005 to 2024.Methods:The literature related to gene therapy for RP included in the Web of Science Core Collection dataset from January 1, 2005 to September 15, 2024 was retrieved and screened. The bibliometrix package of R software was used to analyze the annual trend of the number of publications, citation frequency, distribution of countries/regions of the literature, and distribution of journals containing the articles. CiteSpace software was used to perform keyword clustering analysis and the keywords bursts analysis.Results:A total of 209 articles were included. There was an overall fluctuating upward trend of annual publications from 2005 to 2024, with the highest number of publications in 2023 at 26 (12.4%, 26/209), and the lowest number of publications in 2006 at 2 (0.9%, 2/209). There was an overall increasing trend in the frequency of citations to relevant literature. Corresponding authors from the United States had the highest total number of publications with 98 (46.9%, 98/209). Among authors, Hauswirth from the University of Florida, USA, had the most with 25 (12.0%, 25/209). Among institutions, Columbia University, USA, had the most with 55 (26.3%, 55/209). Among journals, Mol Ther had the most with 25 (12.0%, 25/209), and it had the highest 2023 impact factor of 12.1. Keyword clustering analysis yielded eight valid clusters, namely #0 P23H, #1 AAV, #2 PDE6B,#3 CRB1, #4 RPGR, #5 antisense oligonucleotide, #6 NR2E3, and #7 NRL, which intersected with each other with good continuity. The keywords bursts analysis showed that the keyword with the longest emergence time was RNAi, followed by PDE and PDE6. USH2A, CRB1, CRISPR Cas9, base editing, and ORF15 were keywords that emerged in recent years and were continuously studied. Conclusions:RP gene therapy research literature has shown an increasing trend from 2005 to 2024, with the highest number of publications from research organizations and scholars in the United States. Currently, studies focus on RHO, PDE6B, CRB1, RPGR, NR2E3, and NRL gene. In recent years, there has been a gradual increase in studies on USH2A, CRB1 genes, and the RPGR ORF15 region. CRISPR Cas9 and base editing gene therapy strategies are being developed.

Objective:To investigate the current status of research in gene therapy for retinitis pigmentosa (RP) from 2005 to 2024.Methods:The literature related to gene therapy for RP included in the Web of Science Core Collection dataset from January 1, 2005 to September 15, 2024 was retrieved and screened. The bibliometrix package of R software was used to analyze the annual trend of the number of publications, citation frequency, distribution of countries/regions of the literature, and distribution of journals containing the articles. CiteSpace software was used to perform keyword clustering analysis and the keywords bursts analysis.Results:A total of 209 articles were included. There was an overall fluctuating upward trend of annual publications from 2005 to 2024, with the highest number of publications in 2023 at 26 (12.4%, 26/209), and the lowest number of publications in 2006 at 2 (0.9%, 2/209). There was an overall increasing trend in the frequency of citations to relevant literature. Corresponding authors from the United States had the highest total number of publications with 98 (46.9%, 98/209). Among authors, Hauswirth from the University of Florida, USA, had the most with 25 (12.0%, 25/209). Among institutions, Columbia University, USA, had the most with 55 (26.3%, 55/209). Among journals, Mol Ther had the most with 25 (12.0%, 25/209), and it had the highest 2023 impact factor of 12.1. Keyword clustering analysis yielded eight valid clusters, namely #0 P23H, #1 AAV, #2 PDE6B,#3 CRB1, #4 RPGR, #5 antisense oligonucleotide, #6 NR2E3, and #7 NRL, which intersected with each other with good continuity. The keywords bursts analysis showed that the keyword with the longest emergence time was RNAi, followed by PDE and PDE6. USH2A, CRB1, CRISPR Cas9, base editing, and ORF15 were keywords that emerged in recent years and were continuously studied. Conclusions:RP gene therapy research literature has shown an increasing trend from 2005 to 2024, with the highest number of publications from research organizations and scholars in the United States. Currently, studies focus on RHO, PDE6B, CRB1, RPGR, NR2E3, and NRL gene. In recent years, there has been a gradual increase in studies on USH2A, CRB1 genes, and the RPGR ORF15 region. CRISPR Cas9 and base editing gene therapy strategies are being developed.

Objective To investigate the effects and potential mechanisms of ultrasound-guided thoracic paravertebral block (TPVB) combined with general anesthesia in patients undergoing thoracoscopic surgery. Methods A total of 122 patients undergoing thoracoscopic surgery were selected and randomly divided into control group and tudy group, with 61 patients in each group.The control group received general anesthesia, while the study group received ultrasound-guided TPVB combined with general anesthesia.Clinical data and perioperative indicators were recorded and compared between the two groups.Mean arterial pressure (MAP), heart rate (HR), Visual Analogue Scale (VAS) scores before surgery, 24 hours and 72 hours after surgery, and inflammatory factors[interleukin-6(IL-6), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α)], oxidative stress indicators[malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)]levels before surgery and 72 hours after surgery were compared between the two groups.Postoperative adverse reactions were recorded.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of key molecules mRNA in the Nrf2/Keap1/ARE pathway in the peripheral blood of patients in the two groups. Results There were no statistically significant differences in operative time and intraoperative blood loss between the two groups (P>0.05).The study group had shorter extubation time and indwelling time of drainage tube, less total drainage volume, and less total PCIA drug consumption within 36 hours after surgery and times of patient controlled intravenous analgesia (PCIA) effective compression compared to the control group (P < 0.05).At 24 and 72 hours after surgery, MAP, HR, and VAS scores were higher than preoperative levels in the control group, while VAS scores were higher than preoperative levels in the study group, but MAP, HR, and VAS scores were lower in the study group compared to the control group (P < 0.05).At 72 hours after surgery, serum levels of IL-6, IL-10, TNF-α, and MDA were higher than preoperative levels, while SOD and GSH-Px levels were lower than preoperative levels in both groups.Additionally, the study group had lower serum levels of IL-6, TNF-α, and MDA and higher levels of IL-10, SOD, and GSH-Px compared to the control group (P < 0.05).The total incidence of postoperative adverse reactions was 4.92%(3/61) in the study group, which was lower than 21.31%(13/61) in the control group (P < 0.05).At 72 hours after surgery, the expression levels of Nrf2 mRNA and ARE mRNA in the peripheral blood of patients in the study group were lower than those in the control group, while the expression level of Keap1 mRNA was higher (P < 0.05). Conclusion Compared with general anesthesia, ultrasound-guided TPVB combined with general anesthesia can significantly improve hemodynamic stability and analgesic effects in patients with early-stage lung cancer after thoracoscopic surgery, relieve inflammatory and oxidative stress responses, and decrease the incidence of postoperative adverse reactions.The molecular mechanism may be related to the inhibition of Nrf2/Keap1/ARE signaling pathway activation.

The outbreak of monkeypox has become a global matter of concern since last year. Monkeypox is a zoonotic disease caused by monkeypox virus（MPXV）infection，and in addition to the typical symptom of rash，MPXV infection can cause a series of neurological manifestations，with the potential mechanisms of immune-mediated neurological damage after infection and direct invasion of the virus into the nervous system. This article reviews the neurological manifestations of MPXV infection，so as to facilitate the early identification and diagnosis of the neurological complications of MPXV infection and adopt appropriate prevention and treatment measures in a timely manner.
Monkeypox virus

Objective:To explore application research of intimacy enhancement therapy in the rehabilition of depression patients, and to provide reference for carrying out depression nursing care.Methods:This study was a randomized controlled trial. From September 2022 to September 2023, a total of 84 depression patients and spouse were selected by convenience sampling method and assigned to the experimental group and control group with 42 cases in each group using the random number table method from Nanfang Hospital, Southern Medical University. The control group applied with routine nursing, and the experimental group implemented intimacy enhancement therapy. Before and 8 weeks after intervention, Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Scale (HAMA-17) and Symptom checklist-90 (SCL-90) were used for assessment.Results:Finally, 81 patients completed the study, including 39 in the experimental group, 13 males and 26 females, aged (36.18 ± 10.93) years old, and 42 in the control group, 17 males and 25 females, aged (38.76 ± 10.90) years old. Before intervention, there was no significant difference in HAMD-17, HAMA-17 and SCL-90 (all P>0.05). After 8 weeks of intervention, the scores of HAMD-17, HAMA-17 scores in the experimental group were (21.00 ± 4.49), (25.38 ± 5.16) points, which were lower than (23.76 ± 6.24), (28.48 ± 5.88) points in the control group; the scores of somatization, interpersonal sensitivity, compulsion, anxiety, depression, others, total SCL-90 in the experimental group were (1.25 ± 0.19), (0.69 ± 0.35), (1.40 ± 0.23), (1.17 ± 0.29), (1.18 ± 0.14), (1.22 ± 0.18), (119.69 ± 9.09) points, which were also lower than (1.82 ± 0.26), (1.53 ± 0.36), (1.69 ± 0.39), (1.88 ± 0.38), (1.73 ± 0.35), (1.31 ± 0.17), (146.19 ± 8.97) points of the control group, the differences were statistically significant ( t values were 2.05-13.20, all P<0.05). Conclusions:Intimacy enhancement therapy can effectively alleviate somatic symptoms and improve prognosis of patients with depression.

Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

Objective:To analyze the rules of medication and principles of formulas for the treatment of coronavirus disease 2019 (COVID-19) using the traditional Chinese medicine inheritance support platform (V2.5).Methods:The clinical data, including gender, age, clinical symptoms, frequency of traditional Chinese medicine medication and prescription information, of patients with COVID-19 and asymptomatic infection who were admitted to Hebei COVID-19 designated hospital supported by medical team of First Affiliated Hospital of Hebei University of Chinese Medicine from January to March 2021 were collected. The information data were input into the traditional Chinese medicine inheritance support platform (V2.5). The data mining and analysis were realized by the integrated association rules and complex entropy clustering analysis methods of the software, including the analysis of the frequency of each drug use, drug meridian, taste, and prescription rules, and the new prescriptions were developed.Results:A total of 564 patients (564 prescriptions) were enrolled, involving 200 Chinese herbs, including 357 cases of common COVID-19 and 207 cases of asymptomatic infection. The proportion of women with common COVID-19 was high, and the high incidence age group was 51-70 years old. There was no significant difference in gender of asymptomatic infection, and the high incidence age group was 1-20 years old. The main clinical manifestations of most patients were head heavy and cough, followed by low fever and cough with sputum, the main tongue coating and pulse pattern were similar in both types of patients. The frequency of traditional Chinese medicine used in patients with common type of COVID-19 from high to low was liquorice root (326 times), indian bread (264 times), pinellia tuber (263 times), bitter apricot seed (236 times), baical skullcap root (229 times), gypsum (205 times), agastache rugosus (201 times), dried tangerine peel (194 times), ephedra (184 times), and Chinese thorowax root (163 times), while that used by asymptomatic infection were baical skullcap root (174 times), liquorice root (142 times), medicated leaven (137 times), agastache rugosus (127 times), pinellia tuber (114 times), Chinese thorowax root (100 times), officinal magnolia bark (91 times), atractylodes rhizome (89 times), peony root (84 times), and milkvetch root (83 times). The two types of patients were mainly treated with warm, cold and flat drugs, and the nature and taste were mainly pungent, bitter and sweet. The meridian tropism of drugs was mainly lung, spleen and stomach. High frequency drug formulation mainly included drugs for resolving turbidity and detoxification. At the same time, seven new prescriptions for common COVID-19 and four new prescriptions for asymptomatic infection were developed.Conclusions:The primary reason for the COVID-19 occurrence and development is turbidity-toxin and the qi of plague, and resolving turbidity and detoxication are the basic treating principle. On the basis, for patients with common COVID-19, symptomatic treatment such as relieving exterior syndrome, clearing heat, resolving phlegm, and antitussive drugs should be taken into account at the same time, while the treatment of asymptomatic infections should focus more on supporting the body and eliminating the harmful pathogens.