Objective To observe the effect of catgut implantation at acupoint(CIAA)on the learning and memory function,hippocampal microangiogenesis,and the mRNA and protein expression of angiopoietin-1(Ang-1)/vascular endothelialgrowth factor(VEGF)and its receptor TEK tyrosine kinase(TIE2)/VEGF receptor 2(VEGFR2)in rats with vascular dementia(VD).To explore the mechanism of catgut implantation at acupoint in preventing and treating VD.Methods Using a random number table,VD rats were divided into a model group,a nimodipine group,and an catgut implantation at acupoint group,and a sham operation group was set up,with 10 rats in each group.On the 7th day after surgery,the treatment groups were given catgut implantation at acupoint and nimodipine gastric lavage for 21 days.After treatment,Morris water maze behavioral test was performed.HE staining was used to observe hippocampal CA1 tissue.CD34 immunohistochemical staining was used to detect hippocampal microvascular density(MVD).Real-time PCR and Western blotting were used to detect the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the hippocampus.Results Compared with the model group,the average escape latency of the other groups was significantly shortened,and the target quadrant residence time was significantly prolonged(P<0.01,P<0.05).Compared with the model group,the number of nucleolus and well-formed pyramidal cells in hippocampal CA1 area of the catgut implantation at acupoint group and the nimodipine group increased in varying degrees,and they were arranged more closely,with only a few cells scattered and swollen.In the sham surgery group,a few CD34 positive cells were scattered.The treatment groups had more closely distributed CD34 positive cells with significant staining compared to the model group.The MVD of the model group was significantly higher than that of the sham surgery group(P<0.01).Both nimodipine group and catgut implantation at acupoint group had higher MVD than the model group(P<0.05,P<0.01).Compared with the sham surgery group,the mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2 in the model group increased significantly(P<0.01,P<0.05).Compared with the model group,both nimodipine group and catgut implantation at acupoint group had higher mRNA and protein expression of Ang-1/VEGF and its receptor TIE2/VEGFR2(P<0.01,P<0.05).Conclusion Catgut implantation at acupoint can improve the learning and memory abilities in VD rats,promote hippocampal microvascular angiogenesis,which may be related to the up-regulation of Ang-1/VEGF and its receptor TIE2/VEGFR2 mRNA and protein expression.

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited signif-icant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degra-dation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

Objective:To summarize and analyze the composition characteristics and problems of basic medical insurance policies for traditional Chinese medicine in various provinces of China,providing reference for optimizing and improving subsequent basic medical insurance policies for traditional Chinese medicine.Methods:Based on the perspective of policy instrument,combined with two dimensions of policy instrument types and policy development process,the content analysis method is used to quantitatively analyze the content of the basic medical insurance policies for traditional Chinese medicine released at the provincial level from 2011 to 2023.Results:The 93 included policy documents were coded and sorted,with a cumulative total of 487 codes.From the perspective of policy instrument dimensions,subcategories of policy instruments involve diverse themes,but there are differences in the level of attention paid to each policy tool.From the perspective of policy development process,each link also presents a discrete trend,indicating a dominant feature of policy planning and implementation.Conclusion:To improve the basic medical insurance policy system of traditional Chinese medicine in China,it is necessary to optimize the combination of policy instrument and construct a coordinated and balanced policy instrument framework;Overall planning of the development process of traditional Chinese medicine medical insurance policies,highlighting the unique advantages of traditional Chinese medicine;Emphasize policy synergy between dimensions and strengthen the implementation of traditional Chinese medicine medical insurance policies.

OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.
Animals ; Dementia, Vascular/therapy* ; Electroacupuncture ; Hippocampus/metabolism* ; Immunity ; Myeloid Differentiation Factor 88 ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Toll-Like Receptor 4/metabolism*

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.
Contrast Media ; Diagnosis, Differential ; Epidermal Cyst ; Humans ; Lymphoma ; Male ; Neoplasms, Germ Cell and Embryonal/diagnostic imaging* ; Sensitivity and Specificity ; Testicular Neoplasms/diagnostic imaging* ; Ultrasonography/methods*

The name， origin， place of origin， medicinal parts， harvesting and processing of lotus are verified by consulting ancient Chinese herbal medicines and medical books， combined with modern literature， providing a basis for the development of famous classical formulas containing lotus. According to textual research， the original base of lotus is Nelumbo nucifera since ancient times， rhizome （Nelumbinis Rhizomatis Nodus）， leaf （Nelumbinis Folium）， seed （Nelumbinis Semen）， embryo （Nelumbinis Plumula）， receptacle （Nelumbinis Receptaculum）， stamen （Nelumbinis Stamen） and other medicinal parts of N. nucifera can be used as medicine and have different clinical effects. Nelumbinis Semen was originally produced in Henan， and then gradually expanded to Jiangnan. Today， it can be cultivated and planted throughout the country， with Fujian， Hunan， and Jiangxi as the authentic production areas. After combing the medicinal parts of N. nucifera and the historical evolution of its processing， it is suggested that the dried and mature fruits of N. nucifera taking in autumn and removing the shell and Nelumbinis Plumula should be used in Qingxin Lianziyin. Nelumbinis Folium in Erdongtang should be harvested in summer and autumn， and the raw products was used as medicine and processed in accordance with the provision of the 2020 edition of Chinese Pharmacopoeia.

Based on the ancient literature of all dynasties， this article makes a systematic textual research on the name， origin， producing area， quality， harvesting and processing of Zisu （Perillae） in the famous classical formulas， so as to clarify the information of the drug in different historical periods and provide a reference for the development and utilization of the related formulas. The main origin of Perillae in the ancient literature was Perilla frutescens var. frutescens （purple leaf type）， followed by P. frutescens var. acuta （purple leaf type）， but not Baisu. Modern chemical composition studies also show that there are obvious differences between Perillae and Baisu， which provides a scientific basis for distinguishing them. Although they are often treated as a species in plant classification， P. frutescens var. frutescens （purple leaf type） is recommended in the development of famous classical formulas， and Baisu should be avoided. Perillae is widely distributed， but its producing area did not record in most of the literature in the past dynasties， or the producing area is described as everywhere today. In the period of the Southern and Northern dynasties， the medicinal parts of Perillae included stems， leaves and seeds， and doctors in the Ming dynasty began to pay attention to the differentiation of different medicinal parts. The harvesting and processing methods of Perillae in the past dynasties are close to that of today. Perillae Fructus is mostly stir-fried and ground into medicine， Perillae Folium and Perillae Caulis are mainly simple cleansing. In production， we can refer to the 2020 edition of Chinese Pharmacopoeia.

Based on various ancient documents such as materia medica， prescription books， classics and history， combined with relevant research materials in modern times， this paper made a textual research on the name， origin， geoherbalism， harvesting time， processing methods of Chuanxiong Rhizoma， which provides a basis for the development of famous classical formulas containing this herb. According to the textual research， the original name of Chuanxiong is Xiongqiong （芎䓖）， which was first recorded in Shennong Bencaojing ， there are many aliases and trade names in the past dynasties. Since the Song dynasty， doctors all take Xiongqiong produced in Sichuan as the best medicine， so they take Chuanxiong as the rectification of name. In the early stage， the origin of Chuanxiong Rhizoma was relatively complicated， and the main origin was Ligusticum chuanxiong， which was a cultivated and domesticated species of Ligusticum. However， wild related plants of Ligusticum are still used as medicine. After the Ming dynasty， new cultivated varieties appeared in various places， such as Jiangxi L. sinense cv. Fuxiong， which gradually turned to self-production and self-marketing after the Republic of China. After several changes in the authentic producing area of Chuanxiong Rhizoma， Tianshui in Gansu province was highly praised in the Tang dynasty， and Dujiangyan in Sichuan province was the best place in the Song dynasty and later dynasties. Chuanxiong Rhizoma has been widely used in the past dynasties as raw products， and it has also been processed with excipients. For example， wine-processed products can enhance the effect of promoting blood circulation， promoting Qi circulation and relieving pain. There are other processing methods such as stir-frying and vinegar processing. Chuanxiong Rhizoma in the famous classical formulas can be selected according to this research conclusion.

This paper made a systematic textual research on the historical evolution and changes of the name， origin， producing area， harvesting and processing methods of Jujubae Fructus used in famous classical formulas by referring to the ancient literature， so as to provide a basis for the sampling and research of the formulas containing the medicinal materials. According to textual research， there are many names of Jujubae Fructus， most of which are named by characters or producing areas， which are called Dazao. Ziziphus jujuba has always been the mainstream variety in all dynasties， and Z. jujuba var. inemmis has also been used. Considering that the differences between the two are not obvious， we can use Z. jujuba and Z. jujuba var. inemmis as the origins of Dazao. The germplasm resources of Jujubae Fructus are rich， which are distributed all over the country. Qingzhou （now Shandong）， Jinzhou （now Shanxi） Jiangzhou （now Shanxi）， Puzhou （now Shanxi） have been recorded as authentic producing areas of Jujubae Fructus in the past dynasties， especially in Shandong. At the beginning of the 21^st century， the planting of Jujubae Fructus in Xinjiang gradually developed， and now has a high market recognition， becoming an emerging production area of high-quality samples. Harvest period of Jujubae Fructus is mostly August in the past dynasties， and this is basically the same as today. The main processing method is simple cleansing and drying. Through textual research， it is suggested that Jujubae Fructus in famous classical formulas should be mainly from Shandong， Shanxi and other traditional high-quality producing areas， the processing method should follow the 2020 edition of Chinese Pharmacopoeia for simple cleansing and drying.

Based on the ancient literature of all dynasties， this article makes a systematic textual research on the name， origin， producing area， quality， harvesting and processing of Magnoliae Officinalis Cortex used in the famous classical formulas， and clarifies its information of each link in different historical periods， so as to provide a reference and basis for the development and utilization of the related formulas. The results showed that the main varieties of Magnoliae Officinalis Cortex were Magnolia officinalis or M. officinalis var. biloba. The main production areas are Hubei， Sichuan， Chongqing and other places， forming the famous authentic medicine. The processing methods of the past dynasties are mainly cleansing and processing with ginger. In the formulas clearly marked with ginger processing， ginger-processed products is suggested to choose. If not clearly marked， raw or ginger-processed products can be used as needed.