ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

The pathogenesis of central nervous system （CNS） diseases is complex， seriously affecting patients' physical and mental health and imposing a heavy economic burden on society. Western medicine shows limited efficacy in treating CNS diseases and is often associated with numerous adverse reactions and contraindications. Chinese medicine Lycii Fructus exhibits multiple pharmacological effects， including immune regulation， enhancement of hematopoietic function， liver protection， anti-tumor， hypoglycemic， antipyretic， anti-aging， and anti-radiation activities， and has gradually been applied in clinical treatment. In recent years， the active components of Lycii Fructus have attracted considerable attention for their potential therapeutic effects on CNS diseases. Studies indicate that these active components may exert neuroprotective effects through anti-inflammatory and antioxidant actions， inhibition of neuronal apoptosis， and repair of neuronal damage， involving multiple targets and pathways. This review summarizes the therapeutic effects of Lycii Fructus active components in CNS diseases over the past decade by searching PubMed， CNKI， Wanfang Data， and other electronic databases， aiming to provide new treatment strategies and insights for future research on Lycii Fructus in CNS disorders.

Ankylosing spondylitis(AS)is a chronic inflammatory autoimmune disease characterized by inflammatory back pain.Its pathological features mainly include inflammation,bone destruction,and pathologic new bone formation.The etiology of AS is complex,and it may be related to genetics,infections,the environment,and intestinal flora.Its pathogenesis has not yet been clarified.In recent years,osteoimmunology,as a new theme in the study of inflammatory arthritis,plays an important role in the pathogenesis and development of AS,which was embodied in the inflammatory response and imbalance of bone metabolism.Traditional Chinese medicine(TCM)has the characteristics of multiple pathways,multiple components,multiple targets and multiple levels.TCM can improve the inflammatory response and bone metabolism imbalance of AS by regulating the osteoblasts of the skeletal system and the related factors of the immune system,thus to prevent and control AS.For this reason,the paper summarizes the role of bone immunology in the pathogenesis of AS,and reviews the current status of research on the intervention of TCM in bone immunology for the treatment of AS,with a view to providing certain references for the future clinical application of TCM in the prevention and treatment of AS.

Objective To observe the value of 3.0T multimodal MRI for preoperative evaluation of T stage and therapeutic efficacy of neoadjuvant for rectal cancer.Methods 3.0T multimodal MRI data,including T1WI,T2WI/diffusion weighted imaging(DWI),dynamic contrast enhanced MRI(DCE-MRI)and intravoxel incoherent motion DWI(IVIM-DWI)of 150 patients with rectal cancer were retrospectively analyzed,and the value of different sequences for evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer were assessed.Results The sensitivity,specificity and accuracy of T1WI,T2WI/DWI,DCE-MRI and IVIM-DWI for evaluating T1-T2 and T3-T4 stage rectal cancer were all significantly different(all P＜0.05).The diagnostic efficacy of DCE-MRI and IVIM-DWI were all higher than that of T1WI and T2WI/DWI(all P＜0.05).Combination evaluation of DCE-MRI and IVIM-DWI for T stage of rectal cancer had good consistency with pathological results(Kappa=0.943,P＜0.05).Significant differences of volume transfer constant(Ktrans),true diffusion coefficient(D)and apparent diffusion coefficient(ADC)were found among different T stage rectal cancers(all P＜0.05).Totally 80 patients received neoadjuvant therapy,and significant differences of Ktrans,D and ADC were noticed between patients with good(n=32)or poor efficacy(n=48)(all P＜0.05).The area under the curve(AUC)of Ktrans,D and ADC for evaluating therapeutic efficacy of neoadjuvant for rectal cancer was 0.774,0.837 and 0.758,respectively,of the combination of above three was 0.929,higher than that of single indexes(all P＜0.05).Conclusion Combination of 3.0T DCE-MRI and IVIM-DWI was helpful for preoperative evaluating T stage and therapeutic efficacy of neoadjuvant for rectal cancer.

Constitutively activated G proteins caused by specific mutations mediate the development of multiple malignancies. The mutated Gαq/11 are perceived as oncogenic drivers in the vast majority of uveal melanoma (UM) cases, making directly targeting Gαq/11 to be a promising strategy for combating UM. Herein, we report the optimization of imidazopiperazine derivatives as Gαq/11 inhibitors, and identified GQ262 with improved Gαq/11 inhibitory activity and drug-like properties. GQ262 efficiently blocked UM cell proliferation and migration in vitro. Analysis of the apoptosis-related proteins, extracellular signal-regulated kinase (ERK), and yes-associated protein (YAP) demonstrated that GQ262 distinctly induced UM cells apoptosis and disrupted the downstream effectors by targeting Gαq/11 directly. Significantly, GQ262 showed outstanding antitumor efficacy in vivo with good safety at the testing dose. Collectively, our findings along with the favorable pharmacokinetics of GQ262 revealed that directly targeting Gαq/11 may be an efficient strategy against uveal melanoma.

Objective:By using balloon occlusive hepatic angiography in cirrhotic portal hypertension to evaluate contrast doses on the detection rate of intrahepatic venous-lateral branch shunt (HVVC), and the effect on hepatic venous pressure gradient (HVPG) and portal vein pressure gradient (PPG).Methods:From Jan 2018 to Jun 2021, 131 patients received transjugular intrahepatic portosystemic shunt (TIPS) at Beijing Shijitan Hospital.Results:A positive correlation between PVP and weged hepatic venous pressure (WHVP) ( r=0.241, P=0.001) was found when only by right hepatic vein approach. Ten ml of iodine contrast medium when compared to 5ml doses found more cases of intrahepatic venous-venous lateral branch shunt. The mean PPG of patients with HVVC was significantly higher than the mean of HVPG( P<0.05).The right hepatic vein was the only reliable vein by which WHVP was measured. Conclusions:Right hepatic vein manometry,adequate ballon occlusion and using 10ml of iodine contrast help get reliable WHVP and found HVVC; HVVC can affect the consistency of HVPG and PPG.

Human respiratory tract is colonized with microbial communities. In recent years, high-throughput DNA sequencing technology has subverted the traditional understanding of pulmonary sterility by proving that there are bacteria in the lungs. As research progresses, it is discovered that there is a connection between the gut and respiratory microbiota, known as the " gut-lung axis" . The gut microbiota can influence lung immunity, and lung inflammation can affect the gut microbiota and cause disease. An in-depth understanding of the " gut-lung axis" has given us a deeper understanding of mucosal immunity. The respiratory microbiota may play an important role in the structural maturation of the host airway, the formation of local immunity and the development of the system, and also has an important impact on the occurrence and development of respiratory diseases in children. In recent years, many achievements have been made in microbiological research around respiratory diseases. Attempts to apply microbe-directed therapies (including probiotics, prebiotics and antibiotics and even vaccines) to restore the healthy homeostasis of the respiratory microbiota in diseased states may be an important target for the prevention and treatment of respiratory diseases in the future. The assumption of applying " omics" such as metagenomics, metabolomics, metatranscriptomics and metaproteomics for experimental research may help to gain a deeper understanding of the impact of the respiratory microbiota on respiratory health and disease, and to better understand the function of the respiratory microbiota and causality. Actively searching for novel probiotics or microbiota with anti-inflammatory properties will be a potential candidate approach for improving airway inflammation in the future; further discovery of novel metabolites with immunomodulatory potential as well as the metabolites of purified microorganisms (such as short-chain fatty acids) will provide promising candidates for the treatment of respiratory diseases. This article summarized the progress in this field in recent years.

Objective:To explore the correlation between portal vein pressure gradient (PPG) and hepatic vein pressure gradient (HVPG) in patients with portal hypertension (PHT).Methods:752 cases with portal hypertension (PHT) who underwent transjugular intrahepatic portosystemic shunt (TIPS) and met the enrollment criteria between January 2016 to December 2019 were analyzed for hepatic vein, inferior vena cava and portal vein pressure. Paired t-test was used for analysis. Pearson correlation test was used to estimate correlation coefficient and coefficient of determination. P<0.05 were considered statistically significant. Results:Wedged hepatic vein pressure (WHVP), portal vein pressure (PVP), correlation coefficient, and coefficient of determination were 27.98±8.95 mmHg, 33.85±7.33 mmHg, 0.329 ( P<0.001), and 0.108, respectively. HVPG, PPG,correlation coefficient, and coefficient of determination were 16.84±7.97 mmHg, 25.11±6.95 mmHg ( P<0.001), 0.145, and 0.021 ( P<0.001), respectively. The difference between HVPG and PPG was greater than 5 mmHg in 524 cases, accounting for 69.7%. The difference between HVPG and PPG was within 5 mmHg or basically equal in 228 cases, accounting for 30.3%. The correlation coefficient between free hepatic venous pressure (FHVP) and inferior vena cava pressure (IVCP) was 0.568 ( P<0.001), and the coefficient of determination was 0.323. According to the presence or absence of hepatic venous collaterals after balloon occluded hepatic angiography, they were divided into two groups: 157 (20.9%) cases in the group with hepatic venous collaterals, and 595 (79.1%) cases in the group without hepatic venous collaterals. The parameters of the two groups were compared: WHVP (15.73±3.63) mmHg vs. (31.22±6.90) mmHg, P<0.001; PVP (31.69±8.70) mmHg vs. (34.42±6.81) mmHg, P<0.001; HVPG (7.18±4.40) mmHg vs. (19.40±6.62) mmHg, P<0.001; PPG (24.24±8.11) mmHg vs. (25.34±6.60) mmHg, P<0.001; free hepatic venous pressure (FHVP) (8.58±3.37) mmHg vs. (11.82±5.07) mmHg , P<0.001; inferior vena cava pressure (IVCP) (7.45±3.29) mmHg vs. (9.09±4.14) mmHg, P<0.001. Conclusion:The overall correlation is poor between HVPG and PPG. HVPG of most patients is not an accurate representation of PPG, and the former is lower than the latter. Hepatic venous collateral formation is one of the important reasons for the serious underestimation of HVPG values.

Src homology containing protein tyrosine phosphatase 2 (SHP2) represents a noteworthy target for various diseases, serving as a well-known oncogenic phosphatase in cancers. As a result of the low cell permeability and poor bioavailability, the traditional inhibitors targeting the protein tyrosine phosphate catalytic sites are generally suffered from unsatisfactory applied efficacy. Recently, a particularly large number of allosteric inhibitors with striking inhibitory potency on SHP2 have been identified. In particular, few clinical trials conducted have made significant progress on solid tumors by using SHP2 allosteric inhibitors. This review summarizes the development and structure-activity relationship studies of the small-molecule SHP2 inhibitors for tumor therapies, with the purpose of assisting the future development of SHP2 inhibitors with improved selectivity, higher oral bioavailability and better physicochemical properties.

Objective:To explore whether Internet continuous nursing can reduce anxiety and depression, chemotherapy-induced peripheral neuropathy, improve treatment compliance and reduce adverse reactions in patients with colorectal cancer undergoing oxaliplatin chemotherapy.Methods:A total of 69 patients with colorectal cancer in the Department of oncology, General Hospital of Northern War Zone from July 2019 to June 2020 were selected and divided into the observation group (34 cases) and the control group (35 cases) by random digits table method. The control group was given conventional nursing mode, and the observation group was given Internet continuity nursing mode. All patients were followed up to 3 months after the end of chemotherapy. The basic information, treatment anxiety and depression, chemotherapy-induced peripheral neuropathy, compliance, incidence of adverse reactions and patient satisfaction of the two groups were compared.Results:There was no significant difference in the anxiety and depression before and after chemotherapy, chemotherapy-induced peripheral neuropathy after chemotherapy( P>0.05). After 3 months of chemotherapy, the anxiety and depression and chemotherapy-induced peripheral neuropathy were (20. 97± 3.46),(14.27 ± 1.14) points in the observation group, and (24. 99 ± 1.11),(18.16 ± 2.55) points in the control group, the differences were statistically significant ( t values were 3.80, 5.09, P<0.05). In the control group, there were 19 cases of regular review, 20 cases of persistent chemotherapy, 21 cases of disease awareness, 21 cases of scientific diet, 19 cases of psychological compliance and 19 cases of self-protection. In the observation group, there were 28 cases of regular review, 29 cases of persistent chemotherapy, 30 cases of disease awareness, 28 cases of scientific diet, 30 cases of psychological compliance and 28 cases of self-protection. The treatment compliance in the observation group were significantly higher than those in the control group (χ 2 values were 4.186-9.657, P<0.05). In the control group, there were 7 cases of peripheral neurotoxicity, 2 cases of acute laryngopharyngeal paresthesia, 18 cases of gastrointestinal reaction and 4 cases of hematotoxicity. Fourteen cases of gastrointestinal reaction in the observation group. The incidence of adverse reactions in the observation group was lower than that in the control group, and the difference was statistically significant ( χ2 value was 8.26, P<0.05). In the control group, 6 were very satisfied, 27 were satisfied and 2 were good.The observation group was very satisfied and satisfied with 16 people and 18 people. The satisfaction in the observation group was higher than that in the control group, and the difference was statistically significant ( Z value was 1.853, P<0.05). Conclusions:Internet continuous nursing can effectively reduce the anxiety and depression of patients and chemotherapy-induced peripheral neuropathy, improve the treatment compliance of patients, reduce the adverse reactions after medication, and improve the quality of life of patients, which is worthy of application and promotion.