This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

Objective:To analyze the clinical data of patients with end-stage ankle and hindfoot ar-thropathy who underwent tibiotalocalcaneal(TTC)arthrodesis by the same surgeon,explore the short-and mid-term clinical results,complications and functional improvement,and discuss the clinical progno-sis and precautions of TTC arthrodesis.Methods:Retrospective analysis was made on the clinical data of 40 patients who underwent TTC arthrodesis by the same surgeon from March 2011 to December 2020.In this study,23 males and 17 females were included,with an average age of(49.1±16.0)years.All the patients underwent unilateral surgery.The clinical characteristics,imaging manifestations,main diagno-sis and specific surgical techniques of the patients were recorded.The clinical outcomes were evaluated by comparison of the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score and visual analogue scale(VAS)between pre-operation and at the last follow-up.The fusion healing time,symptom improvement(significant improvement,certain improvement,no improvement or deterioration)and postoperative complications were also recorded.Results:The median follow-up time was 38.0(26.3,58.8)months.The preoperative VAS score was 6.0(4.0,7.0),and the AOFAS score was 33.0(25.3,47.3).At the last follow-up,the median VAS score was 0(0,3.0),and the AOFAS score was 80.0(59.0,84.0).All the significantly improved compared with their preoperative corre-sponding values(P＜0.05).There was no wound necrosis or infection in the patients.One patient suf-fered from subtalar joint nonunion,which was syphilitic Charcot arthropathy.The median bony healing time of other patients was 15.0(12.0,20.0)weeks.Among the included patients,there were 25 cases with significant improvement in symptom compared with that preoperative,8 cases with certain improve-ment,4 cases with no improvement,and 3 cases with worse symptoms than that before operation.Con-clusion:TTC arthrodesis is a reliable method for the treatment of the end-stage ankle and hindfoot ar-thropathy.The function of most patients was improved postoperatively,with little impact on daily life.The causes of poor prognosis included toe stiffness,stress concentration in adjacent knee joints,nonunion and pain of unknown causes.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Objective    To construct a prognostic model of esophageal squamous cell carcinoma (ESCC) based on immune checkpoint-related genes and explore the potential relationship between these genes and the tumor microenvironment (TME). Methods     The transcriptome sequencing data and clinical information of immune checkpoint genes of samples from GSE53625 in GEO database were collected. The difference of gene expression between ESCC and normal paracancerous tissues was evaluated, and the drug sensitivity of differentially expressed genes in ESCC was analyzed. We then constructed a risk model based on survival-related genes and explored the prognostic characteristics, enriched pathway, immune checkpoints, immune score, immune cell infiltration, and potentially sensitive drugs of different risk groups. Results    A total of 358 samples from 179 patients were enrolled, including 179 ESCC samples and 179 corresponding paracancerous tissues. There were 33 males and 146 females, including 80 patients≤60 years and 99 patients>60 years. 39 immune checkpoint genes were differentially expressed in ESCC, including 14 low expression genes and 25 high expression genes. Drug sensitivity analysis of 8 highly expressed genes (TNFRSF8, CTLA4, TNFRSF4, CD276, TNFSF4, IDO1, CD80, TNFRSF18) showed that many compounds were sensitive to these immunotherapy targets. A risk model based on three prognostic genes (NRP1, ICOSLG, HHLA2) was constructed by the least absolute shrinkage and selection operator analysis. It was found that the overall survival time of the high-risk group was significantly lower than that of the low-risk group (P<0.001). Similar results were obtained in different ESCC subtypes. The risk score based on the immune checkpoint gene was identified as an independent prognostic factor for ESCC. Different risk groups had unique enriched pathways, immune cell infiltration, TME, and sensitive drugs. Conclusion     A prognostic model based on immune checkpoint gene is established, which can accurately stratify ESCC and provide potential sensitive drugs for ESCC with different risks, thus providing a possibility for personalized treatment of ESCC.

OBJECTIVE: To evaluate the early effectiveness of a new minimally invasive plate in the treatment of varus-type ankle arthritis. METHODS: A clinical data of 15 patients with varus-type ankle arthritis who met the selection criteria between March 2021 and October 2021 were retrospectively analyzed. All the patients were treated with medial open-wedge supramalleolar osteotomy and fibular osteotomy. The osteotomies were fixed with the new minimally invasive plate. There were 7 males and 8 females with an average age of 49.8 years (range, 16-71 years). The causes of ankle arthritis included post-fracture deformity in 1 case, sprain in 8 cases, and acquired clubfoot in 1 case; and 5 cases were without obvious factors. The disease duration ranged from 1 to 12 years, with an average of 4.1 years. Comparisons were made between pre-operation and the last follow-up in the Takakura staging, the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, foot function index (FFI), visual analogue scale (VAS) score, tibial anterior surface angle (TAS), tibial lateral surface angle (TLS), and talar tilt (TT). RESULTS: All incisions healed by first intention. All patients were followed up 7-18 months (mean, 12.8 months). At last follow-up, the AOFAS ankle-hindfoot score, FFI, VAS score, and Takakura staging significantly improved when compared with the preoperative ones ( P<0.05). X-ray films showed that the osteotomy healed at 3 months after operation. At last follow-up, TAS significantly increased and TT decreased when compared with the preoperative ones ( P<0.05), and the difference in TLS between pre- and post-operation was not significant ( P>0.05). Complications included 1 case of intraoperative screw breakage and 2 cases of nerve injury of the affected foot. None of the patients complained of significant discomfort at the plate placement during follow-up, and no loosening of the internal fixator occurred. Eleven patients were very satisfied with the effeectiveness, while 4 were relatively satisfied. CONCLUSION The new minimally invasive plate for the varus-type ankle arthritis has good early effectiveness in relieving ankle pain, correcting deformity, improving limb alignment and ankle function, and reducing the incidence of postoperative incisional complications.
Female ; Humans ; Male ; Middle Aged ; Ankle ; Ankle Joint/surgery* ; Osteoarthritis/surgery* ; Retrospective Studies ; Tibia/surgery* ; Treatment Outcome ; Adolescent ; Young Adult ; Adult ; Aged

There are 500 species of Viola(Violaceae) worldwide, among which 111 species are widely distributed in China and have a long medicinal history and wide varieties. According to the authors' statistics, a total of 410 compounds have been isolated and identified from plants of this genus, including flavonoids, terpenoids, phenylpropanoids, organic acids, nitrogenous compounds, sterols, saccharides and their derivatives, volatile oils and cyclotides. The medicinal materials from these plants boast anti-microbial, anti-viral, anti-oxidant and anti-tumor activities. This study systematically reviewed the chemical constituents and pharmacological activities of Viola plants to provide a basis for further research and clinical application.
Viola/chemistry* ; Plant Extracts/pharmacology* ; Flavonoids ; Terpenes/pharmacology* ; China

Objective:To evaluate the clinical and radiographic outcomes of tibiotalocalcaneal arthrodesis via the fibula-preserving anterolateral approach.Methods:From March 2018 to February 2021, 23 patients underwent tibiotalocalcaneal arthrodesis via the fibula-preserving anterolateral approach at the Department of Foot and Ankle Surgery, Beijing Jishuitan Hospital.Of them, 15 were males and 8 females. Their average age at surgery was 54.4 years (range, from 28 to 72 years). There were 11 cases of traumatic arthritis, 2 cases of Charcot arthropathy, 6 cases of neurogenic equinovarus, 2 cases of traumatic equinovarus, and 2 cases of Kashin-Beck disease. Comparisons were made between preoperation and the last follow-up in ankle-hindfoot score of American Orthopedic Foot and Ankle Society (AOFAS), visual analogue scale (VAS), foot function index (FFI), hindfoot alignment angle (HA), hindfoot alignment distance (HD), and hindfoot alignment ratio (HR). The tibia-foot angle on lateral weight-bearing and patient satisfaction at the last follow-up and postoperative complications were documented.Results:This cohort were followed up for an average of 24.7 months (from 12 to 48 months). The AOFAS ankle-hindfoot score (78.2 ± 9.2), VAS [2.0 (0.5, 2.0)], FFI [19.0 (10.5, 35.0)], HA (2.7° ± 5.8°), HD [(0.1 ± 0.8) cm] and HR [44.2 (36.4, 59.2)%] at the last follow-up were significantly improved than the preoperative values [43.4 ± 12.7, 4.0 (4.0, 6.0), 98.0 (60.0, 127.0), 22.0° ± 14.3°, (2.2 ± 1.6) cm and 86.0 (66.3, 100.0)%] (all P<0.05). The tibia-foot angle on lateral weight-bearing was 89.0° (87.1°, 90.4°) at the last follow-up. By the Likert scale, 17 cases were very satisfied with the surgery, 4 cases satisfied and 2 cases tolerate, giving a satisfaction rate of 91.3%(21/23). Infection occurred in one case and nonunion in one. Conclusion:Tibiotalocalcaneal arthrodesis via the fibula-preserving anterolateral approach yields good mid- to short-term clinical and radiographic outcomes, showing a strong capability to correct ankle and hindfoot varus and equinus.

In this paper， the name， classification， origin and other aspects of Schizonepetae Herba in the famous classical formulas were researched by referring to the related herbal literature， medical books and prescription books in the past dynasties. The results showed that Schizonepetae Herba first appeared in Shennong Bencaojing （《神农本草经》） as Jiasu， while Jingjie first appeared in Wupu Bencao （《吴普本草》）， and the name of Jingjie was mainly used as the rectification of name in later generations. The name of Jiasu is mostly derived from its smell， and the name of Jingjie is mostly derived from its pronunciation. Schizonepeta tenuifolia has been highly praised in the past as a original material， and its genuine producing area is Jiangsu， Hebei and other places， medicinal part is whole herb with spike. In modern times， the quality of Schizonepetae Herba is best described as having thin stems， green spike， and aroma. In clinical application， the raw products of Schizonepetae Herba is mainly used， and the carbonisata is mainly used for hemostasis. Famous classical formulas of Huaihuasan and Danggui Yinzi are all made of Schizonepetae Spica， so it is recommended to use the dried panicle of S. tenuifolia. In Liangxue Dihuangtang， Schizonepetae Herba Carbonisata is used， therefore， it is suggested to adopt the processing method of Schizonepetae Herba Carbonisata in the 2020 edition of Chinese Pharmacopoeia.

Ephedrae Herba is a commonly used medicine for dispersing wind and cold， which has a long medicinal history. By referring to the herbal literature， medical books and prescription books， this paper intends to carry out herbal textual research on the name， origin， medicinal part， producing area， harvesting and processing methods of Ephedrae Herba in famous classical formulas， in order to provide the basis for the development of relevant famous classical formulas. According to textual research， the main base of ancient Ephedrae Herba was Ephedra sinica. The medicinal part is the herbaceous stems of Ephedrae Herba. Before the Northern and Southern dynasties， the origin of the records was Jindi and Hedong， which is now Shanxi province. In the Northern and Southern dynasties and later generations， the producing area expanded， and now it is mainly distributed in Hebei， Shanxi， Shaanxi， Inner Mongolia， Gansu， Liaoning and other places， among which Inner Mongolia is the main producing area. The harvesting and processing methods in the past dynasties are to harvest the stems in autumn， dry them in the shade or air to 70%-80% dry， and then dry them in the sun. The processing methods in the past dynasties mainly include removing the knots， wine-fried， honey-fried， processing with vinegar and so on， at present， only honey-fried is still in use. Based on the research results， it is suggested that Ephedrae Herba in famous classical formulas should be selected the dry herbaceous stems of E. sinica. If the processing requirements are not indicated， it is suggested to use raw products of Ephedrae Herba.

Aim To study the neuroprotective effect of rhubarb extract on MCAO model rats and explore its mechanism of action. Methods Forty-five SPF male Sprague-Dawley rats were randomly divided into sham group, MCAO group, and MCAO + rhubarb group. MCAO model was prepared by silk plug method, and rhubarb extract was administered at a concentration of 200 mg · kg