ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

ObjectiveTo systematically review the modeling methods and analyzes the model alignment with clinical features of primary dysmenorrhea （PD） in both traditional Chinese medicine （TCM） and western medicine， providing theoretical and practical guidance for establishing the animal models of PD that better reflect the diagnostic and therapeutic characteristics of both TCM and western medicine. MethodsThe literature on PD animal models was searched against domestic and international databases such as PubMed， CNKI， and Wanfang Data. According to the diagnostic criteria of TCM and western medicine， the modeling methods in the literature were summarized， evaluated for strengths and weaknesses， and systematically assessed for clinical concordance rates to identify suitable reference models. ResultsThe available animal models of PD showed the average clinical concordance rates of 43.64% and 61.27% with the clinical features in TCM and western medicine， respectively. Commonly used modeling methods included estrogen administration， physical stimulation， and surgical intervention， with the estrogen combined with oxytocin model and the ice-water bath model being the most studied. The model of Qi stagnation and blood stasis syndrome that was established with the comprehensive stimulation method demonstrated the highest clinical concordance rate. ConclusionCurrent PD animal models primarily replicate dysmenorrhea and simulate menstruation， but they differ from human menstruation to some extent and cannot fully reflect the pathogenesis and physiological characteristics of PD. Moreover， except the cold coagulation and dampness stagnation syndrome and Qi stagnation and blood stasis syndrome， no animal models for other TCM syndromes have been reported， which limits comprehensive TCM research on this disease to a certain extent.

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Ⅹa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin Ⅲ is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Ⅹa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

Venous thromboembolism(VTE)includes deep venous thrombosis(DVT)and pulmonary embolism(PE).Patients in intensive care unit(ICU)are often at a high risk of VTE due to combining many risk factors.Prevention strategies of VTE in critically ill patients are crucial,including identification of risk factors,the risk as-sessment of thrombosis and bleeding,mechanical prophylaxis and drug prophylaxis,effect monitoring,and quality control.Since the risk of VTE in ICU patients is high,the risk of bleeding should not be ignored.It is a challenge for ICU physicians to comprehensively evaluate the risk of thrombosis and bleeding in critically ill patients and im-plement effective preventive and monitoring measures in time.This article reviews the relevant research progress on prevention strategies of VTE in critically ill patients in order to provide clinical evidence for the prophylaxis of VTE in critically ill patients.

Objective:To investigate the interactive effect of mismatch repair (MMR) protein status and adverse clinicopathological features on prognosis of stage Ⅰ-Ⅲ colon cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 1 650 patients with colon cancer of stage Ⅰ-Ⅲ who were admitted to 7 hospitals in China from January 2016 to December 2017 were collected. There were 963 males and 687 females, aged 62(53,71)years. Patients were classified as 230 cases of MMR deficiency (dMMR) and 1 420 cases of MMR proficiency (pMMR) based on their MMR protein status. Observation indicators: (1) comparison of clinicopathological characteristics between patients of different MMR protein status; (2) analysis of factors affecting the survival outcomes of patients of dMMR; (3) analysis of factors affecting the survival outcomes of patients of pMMR; (4) interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The random forest interpolation method was used for missing values in data interpolation. Univariate analysis was conducted using the COX proportional risk regression model, and multivariate analysis was conducted using the COX stepwise regression with forward method. The coefficient of multiplication interaction effect was obtained using the interaction term coefficient of COX proportional risk regression model. Evaluation of additive interaction effects was conducted using the relative excess risk due to interaction ( RERI). Results:(1) Comparison of clinicopathological characteristics between patients of different MMR protein status. There were significant differences in age, T staging, the number of lymph node harvest, the number of lymph node harvest <12, high grade tumor between patients of dMMR and pMMR ( P<0.05). (2) Analysis of factors affecting the survival outcomes of patients of dMMR. Results of multivariate analysis showed that T staging, N staging, the number of lymph node harvest <12 were independent factors affecting the disease-free survival (DFS) of colon cancer patients of dMMR ( hazard ratio=3.548, 2.589, 6.702, 95% confidence interval as 1.460-8.620, 1.064-6.301, 1.886-23.813, P<0.05). Age and N staging were independent factors affecting the overall survival (OS) of colon cancer patients of dMMR ( hazard ratio=1.073, 10.684, 95% confidence interval as 1.021-1.126, 2.311-49.404, P<0.05). (3) Analysis of factors affecting the survival outcomes of patients of pMMR. Results of multivariate analysis showed that age, T staging, N staging, vascular tumor thrombus were independent factors affecting the DFS of colon cancer patients of pMMR ( hazard ratio=1.018, 2.214, 2.598, 1.549, 95% confidence interval as 1.006-1.030, 1.618-3.030, 1.921-3.513, 1.118-2.147, P<0.05). Age, T staging, N staging, high grade tumor were independent factors affecting the OS of colon cancer patients of pMMR ( hazard ratio=1.036, 2.080, 2.591, 1.615, 95% confidence interval as 1.020-1.052, 1.407-3.075, 1.791-3.748, 1.114-2.341, P<0.05). (4) Interaction analysis of MMR and adverse clinicopathological features on survival outcomes. Results of interaction analysis showed that the multiplication interaction effect between the number of lymph node harvest <12 and MMR protein status was significant on DFS of colon cancer patients ( hazard ratio=3.923, 95% confidence interval as 1.057-14.555, P<0.05). The additive interaction effects between age and MMR protein status, between high grade tumor and MMR protein status were significant on OS of colon cancer patients ( RERI=-0.033, -1.304, 95% confidence interval as -0.049 to -0.018, -2.462 to -0.146). Conclusions:There is an interaction between the MMR protein status and the adverse clinicopathological features (the number of lymph node harvest <12, high grade tumor) on prognosis of colon cancer patients of stage Ⅰ-Ⅲ. In patients of dMMR, the number of lymph node harvest <12 has a stronger predictive effect on poor prognosis. In patients of pMMR, the high grade tumor has a stronger predictive effect on poor prognosis.

Objective: To compare 5-year disease-free survival (DFS) and overall survival (OS) rates of laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for stage IB1 and tumor size <2 cm with visible or invisible tumors. Methods: We retrospectively compared the oncological outcomes of 1,484 cervical cancer patients with IB1 and tumor size <2 cm on final pathology, who received ARH (n=899) or LRH (n=585) between January 2004 and December 2016. Patients were divided into visible tumor subgroup (ARH: n=668, LRH: n=444) and invisible tumor subgroup (ARH: n=231, LRH:n=141) according to tumor type. Results: LRH and ARH showed similar 5-year DFS and OS rates (93.3% vs. 93.1%, p=0.997;96.2% vs. 97.5%, p=0.351) in total study population. LRH was not associated with worse 5-year DFS rate (hazard ratio [HR]=0.96; 95% confidence interval [CI]=0.58–1.58; p=0.871) or OS rate (HR=1.37; 95% CI=0.65–2.89; p=0.409) by multivariable analysis. In the visible tumor subgroups, LRH and ARH showed similar 5-year DFS and OS rates (91.9% vs. 91.9%, p=0.933; 95.0% vs. 96.9%, p=0.276), and LRH was not associated with worse 5-year DFS or OS rate (p=0.804, p=0.324). In the invisible tumor subgroups, LRH and ARH also showed similar 5-year DFS and OS rates (97.3% vs. 97.1%, p=0.815; 100% vs. 99.5%, p=0.449), and LRH was not associated with worse 5-year DFS rate (p=0.723). Conclusions Among patients with stage IB1 and tumor size <2 cm, whether the tumor is visible or not, the oncological outcomes of LRH and ARH among cervical cancer patients are comparable. This suggests that LRH may be suitable for stage IB1 and tumor size <2 cm with visible or invisible tumors.

The high incidence of coronavirus disease 2019 (COVID-19) and high mortality of critical patients have posed a great challenge to global public health resources. Currently there are no specific antiviral drugs and vaccines available for COVID-19, which has drawn the attention to the usefulness of convalescent plasma (CP) again, so the application of CP in the adult patients with COVID-19 is reviewed. The main contents include the possible mechanism of CP, the evidence of CP in the treatment of COVID-19 patients, the safety of clinical application of CP and the main factors affecting the clinical effect of CP, which may provide some basis for clinicians to choose CP for the treatment of adult patients with COVID-19.

Objective:To study the relationship between vitamin D level and muscle mass and grip strength in elderly patients with type 2 diabetes mellitus (T2DM).Methods:From May 2016 to January 2018, 201 patients with type 2 diabetes mellitus aged ≥ 60 who were admitted to the Department of endocrinology of Xuanwu Hospital were selected for prospective study. According to 25-hydroxyvitamin D level(25(OH)D), the patients were divided into the vitamin D deficiency group (25(OH)D<20 μg/L, 140 cases) and the non-deficiency group (20 μg/L≤25(OH)D<70 μg/L, 61 cases). The grip strength, walking speed and muscle mass of upper and lower limbs were measured.Physical examination and laboratory examination were carried out.Results:There was no significant difference between the two groups ( P>0.05). The grip strength, upper limb and lower limb muscle contents in the non deficiency group were significantly higher than those in the deficiency group ((33.49±9.43) kg vs.(29.59±10.30) kg, (4.99±1.09) kg vs.(4.57±1.11) kg, (15.69±3.10) kg vs.(14.54±3.03) kg, P=0.01, 0.015, 0.017). Multivariate logistic regression analysis showed that vitamin D deficiency was independently related to grip strength and lower limb muscle mass( OR=1.286, 95% CI: 1.197-1.346, P<0.01; OR=1.231, 95% CI: 1.102-1.283, P<0.05). Conclusion:Vitamin D deficiency is a risk factor for the decrease of grip strength and lower extremity muscle mass in elderly patients with type 2 diabetes.

Recent studies have discovered a selective autophagy-lipophagy, which can selectively identify and degrade lipids and plays an important role in regulating cellular lipid metabolism and maintaining intracellular lipid homeostasis. The process of lipophagy can be directly or indirectly regulated by genes, enzymes, transcriptional regulators and other factors. This review examines the role of lipophagy in reducing liver lipid content, regulating pancreatic lipid metabolism, and regulating adipose tissue differentiation, and summarizes the findings of the molecules (Rab GTPase, enzymes, ion channels, transcription factors, small molecular substances) involved in the regulation of lipophagy, which points to new directions for the treatment of diseases caused by lipid accumulation.
Adipose Tissue ; Autophagy ; Homeostasis ; Lipid Metabolism ; Liver

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004—2010 than that during 2011—2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ²=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.