AIM:To assess the efficacy of intravitreal conbercept for treating neovascular age-related macular degeneration(nAMD)under a treat-and-extend(T & E)regimen.METHODS: A retrospective analysis was conducted on nAMD patients followed over a 2-year period(May 2020 to May 2022). All eyes received three monthly loading intravitreal injections of conbercept, followed by a T& E regimen in which the injection interval was extended by 2 or 4 wk according to disease activity, up to a maximum of 16 wk. When disease activity recurred, the interval was shortened. Patients were divided into initial and non-initial treatment groups based on treatment history. Best-corrected visual acuity(BCVA), central macular thickness(CMT), injection frequency, and intervals between injections over the 24-month follow-up were compared.RESULTS:Totally 27 patients(15 males and 12 females, 33 eyes)were enrolled. In the initial treatment group(18 eyes, mean age 65.72±12.32 y), BCVA significantly improved at 1, 3, and 6 mo(P<0.05), and CMT significantly improved at 1 and 3 mo(P<0.05). In the non-initial treatment group(15 eyes, mean age 69.00±9.21 y), BCVA improved significantly at 3 mo(P<0.05), whereas CMT remained stable(P >0.05). Baseline CMT was similar between the groups(P>0.05). However, significant differences were observed at multiple post-injection time points(P<0.05). The total number of injections did not differ between the groups(P>0.05). Intervals between injections varied, with the majority at 4 and 3-4 mo in the initial and non-initial treatment groups, respectively.CONCLUSION:Initiating intravitreal conbercept therapy under a T & E regimen results in superior visual and anatomical outcomes compared with non-initial treatment.

ObjectiveBased on 16S rDNA technology and molecular biology methods， the molecular mechanism of Shenling Baizhusan in the treatment of diarrhea-predominant irritable bowel syndrome （IBS-D） was investigated. MethodsThe 42 SD rats with SPF were randomly divided into no control group， SLBZS-H， medium （SLBZS-M）， low （SLBZS-L） dose group， positive control group and model group， with 7 rats in each group. The rat model of IBS-D was prepared by ice-cold senna （0.45 g∙mL^-1） gavage （10 mL∙kg^-1） combined with restraint stress for 14 consecutive days. After successful modeling， the corresponding drugs were given to each group with a gavage volume of 10 mL∙kg^-1： The positive group was administered with 2.36 ， 1.18， 0.59 g∙mL^-1 of Shenling Baizhusan in the Positive group and the Model group with the same volume of normal saline for 14 d. The general condition of the rats： Weight， feces， mental state and death were observed and recorded. The body weight， abdominal wall retraction reflex score （AWR） and loose stool rate of rats in each group were measured before （the first day）， after the model （day 14） and after treatment （day 28）. Hematoxylin-eosin staining was used to observe the morphological characteristics of colon tissues of experimental animals. Enzyme-linked immunosorbent assay was used to quantitatively analyze the concentration of inflammatory mediators in the peripheral blood of experimental animals. Western blotting was used to detect the expression levels of key proteins of Toll-like receptor 4 （TLR4）， Toll-like receptor 2 （TLR2）， myeloid differentiation factor 88 （MyD88） and nuclear factor-κB （NF-κB） signaling pathway in rat colon tissue. 16S rDNA technology was used to detect the structural changes of intestinal microbiota in rats. ResultsCompared with Control， the colon of the Model group showed partial mucosal epithelial shedding and inflammatory cell infiltration. The contents of TNF-α， IL-1β， IL-6 and 5-HT in serum increased （P<0.05）， the protein expressions of TLR2， TLR4， MyD88 and NF-κB in colon tissue increased （P<0.05）， the diversity indices of Richness， Chao1， abundance-based coverage estimator（ACE） and Shannon decreased （P<0.05）， and the phylum Firmicutes， Actinobacteria， The relative richness of Bacteroides-H， Lactobacillus and Ligilactobacillus decreased （P<0.05）， while the relative richness of Bacteroidetes， Proteobacteria and Prevotella increased （P<0.05）. Compared with the model group， the colonic structure and organization of the SLBZS-H group， SLBZS-M group， SLBZS-L group and Positive group were clearer， and only a small number of inflammatory cells were present in some areas， and the serum contents of TNF-α， IL-1β， IL-6 and 5-HT were decreased （P<0.05）， TLR2， TLR4， The protein expressions of MyD88 and NF-κB decreased （P<0.05）， and compared with the model group， the diversity indices of Richness， Chao1， ACE and Shannon in the SLBZS-H， SLBZS-M and SLBZS-L groups increased （P<0.05）， and the richness of Firmicutes and Actinobacteria increased （P<0.05）. The richness of Proteobacteria and Prevotella decreased （P<0.05）， and the abundance of Prevotella decreased （P<0.05）， Bacteroides-H， Muribaculum， Lactobacillus and salivarius in the Positive group salivarius （P<0.05）. ConclusionShenling Baizhusan can effectively treat IBS-D， and its molecular mechanism may be to play a therapeutic role by improving intestinal flora and inhibiting the TLRS/MyD88/NF-κB signaling pathway to reduce inflammatory response.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia（FD） and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats（7 days old） were randomly divided into the normal group（n=12） and the modeling group（n=48）， and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared， the rats in the modeling group were randomly divided into the model group， the low-dose and high-dose groups of Xingpi capsules（0.135， 0.54 g·kg^-1） and the domperidone group（3 mg·kg^-1）， with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water， and rats in the rest of the groups were gavaged with the corresponding medicinal solution， once a day for 7 d. The general survival condition of the rats was observed， and the water intake and food intake of the rats were measured， the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment， the pathological damage of the rat duodenum was examined by hematoxylin-eosin（HE） staining， and the expressions of colonic tight junction protein（Occludin） and zonula occludens protein-1（ZO-1） were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group， and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration， and Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were carried out. The transcriptomic results were validated by Western blot， immunofluorescence， and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group， the general survival condition of rats in the model group was poorer， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly reduced（P<0.05）， inflammatory infiltration was seen in duodenal pathology， and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced（P<0.01）. Compared with the model group， the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly， and the water intake， food intake， gastric emptying rate and small intestinal propulsion rate were all significantly increased（P<0.05）， the duodenal pathology showed a decrease in inflammatory infiltration， and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased（P<0.01）. Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt） through the key genes such as Slc5a1， Abhd6. The validation results showed that compared with the normal group， the phosphorylation levels of PI3K and Akt proteins， the protein expression level of interleukin（IL）-1β， and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3， Slc5a9 and other key genes were significantly increased（P<0.01）. Compared with the model group， the phosphorylation levels of PI3K and Akt， the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced（P<0.05， P<0.01）， and the mRNA levels of Slc5a1， Abhd6， Mgam， Atp1a1， Slc7a8， Cdr2， Chrm3 and Slc5a9 were significantly reduced（P<0.05）. Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein， and linarionoside A， valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats， its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum， and E-nerolidol， Z-nerolidol， linarionoside A， valerosidatum and senkirkine may be its key active ingredients.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Objective:To investigate the optimal delay time in the quantitative assessment of myocardial fibrosis based on dual-energy CT extracellular volume fraction (DECT-ECV), using MRI as a reference.Methods:Thirty patients with confirmed or suspected of cardiomyopathy were prospectively enrolled in this study. All the patients underwent both cardiac DECT and MRI examination within one week. According to the imaging features of late gadolinium enhancement (LGE) on MRI, myocardial segments were classified into 3 types: ischemic LGE segments, non-ischemic LGE segments and negative LGE segments. According to the DECT delay time, the whole and segmental myocardium were divided into 3 groups: delay of 3 min (Group A), delay of 5 min (Group B) and delay of 7 min (Group C). Correlation and agreement between CT-ECV and MRI-ECV were performed on a basis of overall myocardium and segmental myocardium. Pearson or Spearman test was used for correlation analysis and Bland-Altman test was used for consistency analysis.Results:Thirty patients with 480 segments were finally included in our study. In the analysis based on overall myocardium, MRI-ECV was 33.12%±4.29%, and CT-ECV were 35.81%±4.48%, 36.02%±4.56%, and 36.58%±4.69% in Group A, B, and C, respectively. The agreement between DECT-ECV and MRI-ECV results was good, with the correlation coefficients of 0.878 (group A), 0.955 (Group B) and 0.947 (Group C) (all P<0.001). In the analysis based on segmental myocardium, as for the ischemic LGE myocardial segments, MRI-ECV was 34.60%(31.70%,39.40%), and CT-ECV were 37.50 (34.20, 41.90), 38.20%(36.20%, 40.60%)and 39.40%(35.50%,42.40%)in Group A, B, and C, respectively. The agreement between DECT-ECV and MRI-ECV results was good, with the correlation coefficients of 0.559, 0.695 and 0.682 (all P<0.001) for groups A, B and C, and as for non-ischemic LGE myocardial segments, MRI-ECV was 35.10% (32.68%, 38.70%), and CT-ECV were 38.15% (35.13%, 41.75%), 39.25% (35.78%, 42.20%) and 39.60% (35.88%,42.90%) in Group A, B, and C. The correlation coefficients of CMR-ECV and DECT-ECV of groups A, B and C were 0.531, 0.772 and 0.744 (all P<0.001), showing good agreement; as for negative LGE myocardial segments, MRI-ECV and CT-ECV of Group A, Group B, Group C were 28.50%(27.00%, 30.10%), 31.10%(28.70%, 34.60%), 31.30%(28.40%, 33.80%), 31.30%(29.20%, 34.80%). The correlation coefficients between MRI-ECV and DECT-ECV of group A, B and C were 0.273, 0.508 and 0.425 (all P<0.001), which also showed good agreement. Conclusions:DECT-ECV can be used for quantitative evaluation of myocardial histological features. DECT-ECV with a 5 min and 7 min delay shows good correlation and agreement with MRI-ECV. In order to make this technology more well-known and improve its application capability, our recommendation for clinical practice is a 5 min delay after contrast administration in clinical practice.

Objective To investigate the effect of acupuncture on fatigue improvement and gut microbiota in mice with cancer-related fatigue(CRF),and explore its possible mechanism of action.Methods The mice model of CRF of breast cancer after chemotherapy was established by tumor bearing and chemotherapy.After acupuncture intervention,fatigue was evaluated by general condition,forced swimming and open field experiment.Then 16S rDNA sequencing was used to analyze the structural abundance of gut microbiota in mice.Results Acupuncture could significantly improve the fatigue degree and general condition of the mice model of CRF of breast cancer after chemotherapy.At the same time,acupuncture could adjust the abundance of gut microbiota structure,up-regulate the abundance levels of Lactobacillus,Bacteroides,firmicutes,actinobacteria,and down-regulate the abundance levels of Proteobacteria and Staphylococcus.There were also differences in the abundance of flora structure among the groups,but the abundance of beneficial bacteria was relatively high in the acupuncture group,and the abundance of pathogenic bacteria was relatively high in the other two groups.Conclusion Acupuncture may play a role in the treatment of CRF by regulating the abundance of gut microbiota structure,increasing intestinal beneficial bacteria,inhibiting pathogenic bacteria,improving body immunity,and alleviating adverse reactions caused by chemotherapy for breast cancer.

ObjectiveTo explore the possible mechanism of Tongdu Xingshen needling method （通督醒神针刺法） on post-stroke cognitive impairment. MethodsSD rats were randomly divided into a normal group （n=12）， a sham surgery group （n=12）， a model group （n=12）， and a electroacupuncture group （n=13）. The rats in the model group and electroacupuncture group were subjected to the wire bolus method to establish the rats model with learning memory impairment after cerebral ischaemia-reperfusion. After successful modelling， the rats in the electroacupuncture group were given electroacupuncture interventions at “Shenting （GV 24）” and “Baihui （GV 20）” once a day for 30 minutes for 14 days. The other three groups did not receive other interventions but grasp. A 5-day localisation navigation experiment was conducted on the 9th day of intervention， and a spatial exploration experiment was conducted on the 14th day of intervention to evaluate the learning and memory abilities of the rats. After the spatial exploration experiment， hippocampal tissues were taken from each group of rats， and the changes in the volume of cerebral infarction were observed by TTC staining； the changes in the morphology of pyramidal neurons and the density of dendritic spines in the CA1 area of the hippocampus were observed by Golgi staining； protein immunoblotting was used to detect the relative protein expression of the subunits of the α-amino-3-carboxy-5-methylisoxazole-4-propionic acid （AMPA） receptor including glutamate receptor 1 （GluR1）， glutamate receptor 2 （GluR2）， glutamate receptor 3 （GluR3） and auxiliary proteins TARPγ2， TARPγ8 in hippocampal tissues of rats in each group； the real-time fluorescence quantitative PCR was used to detect GluR1， GluR2， GluR3 mRNA levels in the hippocampal tissues of rats. ResultsIn the localisation navigation experiment， compared with the normal group and sham surgery group， the escape latency and total distance of rats in the model group were significantly extended （P＜0.05） at day 1， 2， 3， 4， and 5； and the escape latency and total distance of rats in the electroacupuncture group tended to be significantly shorter than those in the model group （P＜0.05）. In the spatial exploration experiment， compared with the normal group and the sham surgery group， the number of rats crossing the platform in the model group was significantly reduced （P＜0.05）， and the number of crossings of the platform in the electroacupuncture group increased significantly （P＜0.05）. The results of TTC staining showed that the volume of cerebral infarction increased clearly in the model group compared with the sham surgery group （P＜0.05）， and apparently decreased in the electroacupuncture group compared with the model group （P＜0.05）. Golgi staining showed that the number of dendritic branches of pyramidal neurons and dendritic spines in hippocampal CA1 region significantly decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The number of dendritic branches of pyramidal neurons and the density of dendritic spines in hippocampal CA1 region significantly increased in the electroacupuncture group compared with the model group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus decreased in the model group compared with the normal group and the sham surgery group （P＜0.05）. The protein relative expression levels of GluR1， GluR2， GluR3， TARPγ2 and TARPγ8， and the mRNA levels of GluR1， GluR2 and GluR3 in hippocampus increased in the electroacupuncture group compared with model group （P＜0.05）. ConclusionThe Tongdu Xingshen needling method can improve learning memory impairment after cerebral ischaemia-reperfusion， which may be related to up-regulation of the expression of AMPA receptor and their auxiliary protein TARP， and promoting the synaptic plasticity of hippocampal tissues.

Maxillary sinus floor augmentation using lateral window and crestal technique is considered as predictable methods to increase the residual bone height; however, this surgery is commonly complicated by Schneiderian membrane perforation, which is closely related to anatomical factors. This article aimed to assess anatomical factors on successful augmentation procedures. After review of the current evidence on sinus augmentation techniques, anatomical factors related to the stretching potential of Schneiderian membrane were assessed and a decision tree for the rational choice of surgical approaches was proposed. Schneiderian membrane perforation might occur when local tension exceeds its stretching potential, which is closely related to anatomical variations of the maxillary sinus. Choice of a surgical approach and clinical outcomes are influenced by the stretching potential of Schneiderian membrane. In addition to the residual bone height, clinicians should also consider the stretching potential affected by the membrane health condition, the contours of the maxillary sinus, and the presence of antral septa when evaluating the choice of surgical approaches and clinical outcomes.
Sinus Floor Augmentation ; Decision Trees