ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

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Acceleration of tooth movement during orthodontic treatment is challenging,with osteoclast-mediated bone resorption on the compressive side being the rate-limiting step.Recent studies have demonstrated that mechanoreceptors on the surface of monocytes/macrophages,especially adhesion G protein-coupled receptors(aGPCRs),play important roles in force sensing.However,its role in the regulation of osteoclast differentiation remains unclear.Herein,through single-cell analysis,we revealed that CD97,a novel mechanosensitive aGPCR,was expressed in macrophages.Compression upregulated CD97 expression and inhibited osteoclast differentiation;while knockdown of CD97 partially rescued osteoclast differentiation.It suggests that CD97 may be an important mechanosensitive receptor during osteoclast differentiation.RNA sequencing analysis showed that the Rap1a/ERK signalling pathway mediates the effects of CD97 on osteoclast differentiation under compression.Consistently,we clarified that administration of the Rap1a inhibitor GGTI298 increased osteoclast activity,thereby accelerating tooth movement.In conclusion,our results indicate that CD97 suppresses osteoclast differentiation through the Rap1a/ERK signalling pathway under orthodontic compressive force.

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Non-arteritic anterior ischemic optic neuropathy (NAION) is a disease characterized by acute, painless visual acuity loss and visual field impairment, and there is still lack of unified and effective treatment.As new therapeutic strategies, neuroprotection and nerve regeneration have aroused wide public concern, which aim to prevent degeneration and death of neurons or establish a new neural circuit through inhibiting apoptosis pathway and inflammation, promoting axon growth and applying stem cells.Plenty of studies have applied the strategies to NAION patients or NAION animal models, which achieved certain success, but the limitations exist at the same time.For the sake of exploring practical therapies of NAION, researches on the neuroprotection and nerve regeneration strategies of NAION in recent years were reviewed in this article.

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

【Objective】 To understand the epidemic status of drug-resistant Mycobacteriun tuberculosis in Xi’an in the past three years, and the impact of COVID-19 epidemic during 2020 so as to provide basic information for local multidrug-resistant tuberculosis (MDR-TB) prevention and treatment. 【Methods】 Tuberculosis (TB) detected by sputum culture, the corresponding drug susceptibility tests data, and basic clinical information of TB patients diagnosed in Xi’an from January 2018 to October 2020 were collected from the management system; then the epidemic status and the drug resistance status were analyzed. Multinomial logistic regression was used to analyze the relationship between the patients’ treatment history and the drug resistance of TB strains, and the trend of changes in the drug resistance rate in retreated patients. 【Results】 In the past three years, there was a total drug resistance rate of 25.3% in 5 146 strains of MTB, and 24.8% in treatment initiation and 38.22% in retreatment, respectively. The treatment initiation patients showed a decreased MDR-TB detection rate, and the retreated patients had an increased MDR-TB detection rate. The spectrum of MDR-TB in the retreated patients gradually became more complicated, and the resistance rate of second-line drugs such as Kanamycin and Ofloxacin gradually increased. There were 10 drug-resistant combinations mainly in H+R+S and H+R+S+E. During the year 2020 of COVID-19 epidemic, the number of initial and retreated patients decreased significantly compared with that in 2018 and 2019, but with no difference in the drug-resistance rate. There was an increasing detection rate of PDR and MDR-TB strains in the retreated patients. Multinomial logistic regression results showed that in 2020 the retreated patients had 4.28 times of developing PDR-TB (P=0.001, 95% CI=1.417-12.930), and 5.378 times of developing MDR-TB (P<0.001, 95% CI=2.641-10.952) than patients of treatment initiation. 【Conclusion】 In the past three years, the prevention and control of drug-resistant TB in Xi’an has achieved some progress, but drug resistance in retreated patients is still serious. To avoid and reduce the development of drug-resistant TB, precise and active intervention measures should be taken, and health management of TB patients should be strengthened, especially during the current period of COVID-19 epidemic prevention and control.

Objective To investigate the relationship between vWF levels and ADAMTS13 levels of DVT (venous thrombosis) in patients with cervical cancer,and then to evaluate the predictive value of vWF levels and ADAMTS13 levels of cervical cancer patients with DVT. Methods A total of sixty-six patients diagnosed as cervical cancer and treated from June 2015 to June 2016 in Weinan Maternal and Child Health Hospital were enrolled,and their baseline data,pathological type,tumor classification,TNM staging,vWF, ADAMTS13 levels and Autar score were recorded. All patients were followed up for 1 year and the patients with adverse outcomes were defined as poor prognosis group during the follow-up period while the patients whose disease progression free were defined as good prognosis group. Univariate analysis showed that the incidence of venous thrombosis in patients with cervical cancer was affected; Cox proportional hazard model further assessed the impact of all statistically significant factors on the occurrence of venous thrombosis in patients; t test showed the distribution of influential factors between the two groups; ROC curve was used to analyze the sensitivity and specificity of vWF and ADAMTS13 levels in predicting the occurrence of venous thrombosis in cervical cancer patients. Results At the end of the follow-up,among the 66 patients,Six were not followed and 40 had good prognosis without venous thrombosis,which was a good prognosis group; Twenty had poor prognosis,i. e. venous thrombosis,which was a poor prognosis group,including 5 deaths. The poor prognosis rate was 30. 30%. Univariate Cox proportional hazard model results showed that vWF (P＝0. 023, (95%CI: 1. 743－1. 215)) and ADAMTS13 (P＝0. 037,(95%CI: 1. 158－1. 566)) had a significant effect on the patients with venous thrombosis. The levels of vWF (( 0. 535 ± 0. 075) μg/L) and ADAMTS13 ((69. 453±10. 284)%) in good prognosis group were significantly lower than those in poor prognosis group ((0. 592 ± 0. 082 ) μg/L, ( 79. 245 ± 11. 477 )%), and the differences between the two groups were statistically significant (t＝2. 690,3. 345,P＜0. 05). Under ROC curve,the AUC of vWF level was 0. 841,the sensitivity and specificity were 55% and 97. 5% respectively,and that of ADAMTS13 level was 0. 906,the sensitivity and specificity were 85% and 80%,respectively. Conclusion The levels of vWF and ADAMTS13 have a good predictive effect on the occurrence of venous thrombosis in patients with cervical cancer. It is expected to be used as a routine evaluation index to predict the occurrence of venous thrombosis in patients with cervical cancer after treatment.

Objective To evaluate the histocompatibility of an original Chinese-made mid-urethral sling (Repelvica mid-urethral sling). Methods In total 10 female New Zealand white rabbits were implanted with Repelvica mid-urethral sling or tension-free vaginal tape-obturator tape (TVT-O;Gynecare). Both brands of sling were implanted under deep fascia of the abdominal wall and in the space between vagina and bladder. All animal groups were sacrificed at set time intervals (4 weeks and 12 weeks), and the abdominal and vaginal slings were harvested for histological evaluation. Results All slings appeared to be well incorporated into the abdominal wall and anterior vaginal wall. All specimens showed a thin, loose, fibrous interface between the synthetic graft and abdominal wall or vaginal wall, along with mild inflammatory reaction from 4 weeks to 12 weeks. Abdominal grafts of Repelvica mid-urethral sling and TVT-O induced comparable tissue reaction (histological score 10.5 versus 10.5 at 4 weeks, 10.0 versus 9.5 at 12 weeks; both P>0.05). Vaginal grafts of Repelvica mid-urethral sling had lower histological score than TVT-O (histological score 6.0 versus 12.0 at 4 weeks, 8.5 versus 12.5 at 12 weeks), however the differences were not statistically significant (both P>0.05). Conclusions Chinese-made Repelvica mid-urethral sling exhibits good histocompatibility. Vaginal graft of Repelvica mid-urethral sling evoks minor tissue reaction,which could be attributed to its lightweighted property and favored its clinical application.