Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

Objective:To analyze the research progress, hot spots and future trends of standardized residency training of Traditional Chinese Medicine from 1998 to now by using CiteSpace knowledge map software.Methods:The related literature on standardized residency training of Traditional Chinese Medicine were retrieved on CNKI. And after Refworks format conversion, using CiteSpace 5.6 R3 software for the construction of knowledge map, the author cooperation, institutional cooperation, keyword co-occurrence, and time-sharing research hot spots views of related literature on standardized residency training of Traditional Chinese Medicine were drawn respectively.Results:A total of 259 papers were obtained, with 253 authors. Ren Xianqing and Cui Jin published the most articles (each with 4 papers), and Beijing University of Chinese Medicine published the most articles (with 23 papers). There were 259 keywords in total, and 16 keywords with frequency greater than 5 and centrality greater than 0.1. There were 14 keyword cluster tags, and 15 burst terms were detected in total, and the trend discussion was carried out accordingly.Conclusion:The research trend of the standardized residency training of Traditional Chinese Medicine mainly follows the relevant policies issued by the functional departments of the government, and the research hot spots depend on the obstacles and difficulties encountered in the practical application of each training base.

Objective:To evaluate the effect of sleep deprivation on cognitive function in septic rats and its relationship with neuronal glycolysis isoenzyme phosphofructokinase-2/fructose-2,?6-diphosphatase 3 (PFKFB3).Methods:Fifty-six healthy male Sprague-Dawley (SD) rats were randomly divided into 4 groups ( n = 14): control group (Con group), sepsis group (LPS group), sepsis+sleep deprivation group (LPS+SD group), sepsis+sleep deprivation+glycolysis inhibitor 3-PO treatment group (LPS+SD+3-PO group). The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg. Rats in LPS+SD group were treated with sleep deprivation using a sleep deprivation instrument 24 hours after LPS injection. The LPS+SD+3-PO group was intraperitoneally injected with LPS for 24 hours, and then injected with 3-PO 50 mg/kg, followed by sleep deprivation. Novel object recognition experiments were performed 72 hours after LPS injection. Subsequently, blood and brain tissue samples were collected. The contents of lactate (Lac), reactive oxygen species (ROS) and serum tumor necrosis factor-α(TNF-α), neuron-specific enolase (NSE), pyruvate in brain tissue were detected by enzyme-linked immunosorbent assay (ELISA). Then, the lactate/pyruvate ratio was calculated. Na +-K +-ATPase activity in brain tissue was detected by colorimetry. Morphological changes in hippocampus were detected by hematoxylin-eosin (HE) staining. And the protein expression levels of PFKFB3, ZO-1 and cleaved caspase-3 were measured by Western blotting. Results:Compared with Con group, the novel object recognition index of LPS group was decreased, the levels of NSE, TNF-α, lactate/pyruvate ratio in serum and the levels of Lac, ROS and dry-wet weight ratio in brain tissue were significantly increased, Na +-K +-ATPase activity in brain tissue was decreased, the protein expressions of PFKFB3, caspase-3 were up-regulated, ZO-1 expression was down-regulated, and the neurons in hippocampus were slightly degenerated. Compared with LPS group, the novel object recognition index of LPS+SD group was further decreased [(39.4±5.3)% vs. (54.5±7.6)%)], serum NSE, TNF-α, lactate/pyruvate ratio and brain tissue Lac, ROS, dry-wet weight ratio were further increased [NSE (μg/L): 3.21±0.42 vs. 2.55±0.36, TNF-α (ng/L): 139.4±19.7 vs. 92.2±13.5, lactate/pyruvate ratio: 29.7±5.5 vs. 19.2±4.2, Lac (μmol/g): 19.51±2.33 vs. 11.34±1.52, ROS (kU/g): 117.4±18.7 vs. 78.2±11.8, dry-wet weight ratio: (81.3±9.2)% vs. (64.3±6.6)%], and Na +-K +-ATPase activity was further decreased (mmol·L -1·h -1: 1.88±0.34 vs. 2.91±0.39), the protein expressions of PFKFB3, caspase-3 were further up-regulated and ZO-1 expression was further down-regulated (PFKFB3/β-actin: 0.80±0.11 vs. 0.45±0.07, caspase-3/β-actin: 0.71±0.09 vs. 0.37±0.05, ZO-1/β-actin: 0.31±0.05 vs. 0.61±0.08). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly aggravated. Compared with LPS+SD group, the novel object recognition index of LPS+SD+3-PO group was increased [(50.8±5.9)% vs. (39.4±5.3)%], NSE, TNF-α, lactate/pyruvate ratio of serum and Lac, ROS, dry-wet weight ratio of brain tissue were significantly decreased [NSE (μg/L): 2.60±0.33 vs. 3.21±0.42, TNF-α (ng/L): 103.7±18.3 vs. 139.4±19.7, lactate/pyruvate ratio: 17.4±5.1 vs. 29.7±5.5, Lac (μmol/g): 13.68±2.02 vs. 19.51±2.33, ROS (kU/g): 86.9±14.5 vs. 117.4±18.7, dry-wet weight ratio: (67.7±6.9)% vs. (81.3±9.2)%], and Na +-K +-ATPase activity was increased (mmol·L -1·h -1: 2.82±0.44 vs. 1.88±0.34). The protein expressions of PFKFB3, caspase-3 were down-regulated and ZO-1 expression was up-regulated (PFKFB3/β-actin: 0.50±0.06 vs. 0.80±0.11, caspase-3/β-actin: 0.43±0.06 vs. 0.71±0.09, ZO-1/β-actin: 0.52±0.06 vs. 0.31±0.05). The differences were statistically significant (all P < 0.05). HE staining showed that the degeneration of neurons in hippocampus was significantly improved. Conclusions:Sleep deprivation could aggravate neuroinflammation, neuronal degeneration and apoptosis in septic rats, resulting in destruction of blood-brain barrier and cognitive impairment. 3-PO treatment significantly alleviate the injury and degeneration of hippocampal neurons in septic rats, inhibit neuroinflammation and apoptosis, and improve cognitive dysfunction, which may be related to the inhibition of glycolytic isoenzyme PFKFB3.

“Cold-dampness entering ying （营）” is the key to the worsening of cold-dampness epidemic， and is more common in the elderly or critically ill cases of cold-dampness epidemic with pathogen exuberance and healthy qi deficiency. This paper reported a case of critically ill COVID-19 combined with multiple organ dysfunction treated by integrative traditional Chinese and western medicine based on “cold-dampness entering ying” theory. The patient did not have high fever after being infected with SARS-Cov-2， but D-dimer continued to increase， and she developed multiple thrombosis throughout the body and multiple organ dysfunctions such as pulmonary embolism， edema， oliguria， and shock. The patient were with enlarged and dusky tongue， with yellow， thick and greasy coating， and sublingual blood stasis， and thready， rapid and rough pulse. All these were characteristic manifestations of “cold-dampness entering ying”， and was differentiated as cold-dampness stasis. For the treatment， symptomatic and supportive western medicine of improving heart function， anti-infection， relieving asthma， stopping cough and reducing phlegm was given as the basic therapy， and additionally， traditional Chinese medicine to open the constraint and the blocked， save from collapse and restore yang， boost qi and relieve collapse， invigorate blood and drain water was used， usually with Modified Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤加减）， which was in accordance with the pathogenesis and thus achieving good effect.

This paper reported a case of severe COVID-19 in the recovery stage with acute lymphoblastic leukemia treated by integrated traditional Chinese and western medicine， with the intention of shedding light on the clinical diagnosis and treatment of similar conditions. The patient， who had acute lymphoblastic leukemia， developed COVID-19 infection during the bone marrow suppression period after chemotherapy. Treatment with western medicine was mainly anti-infection， symptomatic management， and supportive care. During the recovery stage， considering the patient's chemotherapy history and disease progression， the overall syndrome was identified as deficiency of both qi and yin and binding of phlegm and blood. Based on the “state-target” combined treatment strategy， herbal prescriptions were selected and modified to address the “deficiency state”， “disease target”， and “symptom target”. In addition to western medicine， the patient was administered with Shengmai Powder （生脉散） and Compound Zhebei Granules （复方浙贝颗粒） in its modifications to boost qi， nourish yin， and reinforce healthy qi， nourish and cool the blood， ultimately achieving satisfactory therapeutic effects.

We reported a case of a patient dignosed as tuberculosis and severe malnutrition with coronavirus disease 2019 （critical type） treated with a combination of Chinese medicine and Western medicine. Through the retrospective analysis of the diagnosis and treatment process of this patient， on the basis of Chinese medicine's understanding of the etiology and pathogenesis of “old state” and “deficient state”， the critical coronavirus pneumonia combined with pulmonary tuberculosis and severe malnutrition was mostly due to the physical condition and the invasion of epidemic toxin， resulting in dysfunctions of the internal organs such as the lungs， spleens， kidneys and other organs. Based on the understanding of the cause and mechanism of the coronavirus disease， the treatment combined Chinese and Western medical therapies was given. The western medicine was used with the main treatments of oxygen therapy， anti-viral， intestinal nutritional support， and anti-coagulation， while the Chinese medicine was used by tonifying qi， blood， yin， and yang， warming yang and dissipating cold， and clearing heat and dampness， then tonifying qi， nourishing yin and eliminating heat， in which tonifying middle and replenishing qi ran through the whole process. The integrated treatment eventually improved the patient's symptoms and accelerated the negative conversion of nucleic acid of the coronavirus.

Objective:To explore the value and feasibility of abbreviated comprehensive geriatric assessment(aCGA)grading in elderly patients with breast cancer.Methods:From June 2019 to January 2020, elderly patients with breast cancer aged 65 years and above were enrolled.Eastern Cooperative Oncology Group(ECOG)score and aCGA classification were performed respectively.Clinical characteristics, score distribution and differences between the two assessment methods were compared and analyzed.Results:A total of 61 cases of breast cancer patients aged 65 years and above were included in our study.According to the assessment of aCGA, grade A accounted for 65.5%(40/61), grade B accounted for 27.9%(17/61), and grade C accounted for 6.6%(4/61), among which 82.0%(50/61 cases)of the patients had complications.And the most common complications were hypertension, cardiovascular disease and diabetes.Among the 50 patients with ECOG score 0-1, 74.0%(37/50)were aCGA grade A, and 26.0%(13/50)were aCGA grade B.Conclusions:According to the aCGA grading, about two thirds of breast cancer patients over 65 years old are assessed as grade A, which indicates that they might have better tolerance during the treatment.However, among the patients with 0-1 score according to the ECOG score, some patients still have a slightly worse grade(aCGA grade B, which shows slightly worse health condition), suggesting that the refinement degree of ECOG score may be insufficient, and the health damage of some patients may be underestimated.

Objective:To analyze the prevalence of influenza B virus and its HA and NA genes characteristics during 2017—2020 in Songjiang district, Shanghai.Methods:Samples from suspected cases of influenza were detected using real-time fluorescence reverse transcription-polymerase chain reaction. Influenza B virus positive specimens were cultured by MDCK cells and embryonated chicken eggs. The hamagglutinin (HA) and neuraminidase (NA) genes of influenza virus B strains were sequenced and analyzed for gene evolution and amino acid variation. The sensitivity of the strains to oseltamivir and zanamivir was studied by neuraminidase inhibition assay.Results:The positive rate of influenza B virus in Songjiang district from 2017 to 2020 was 14.24% (506/3554). Influenza B virus circulated mainly in winter-spring season and alternated between B/Victoria and B/Yamagata subtypes. Subclade 1A (△3) B was the predominant Victoria lineage circulating in Songjiang district. Otherwise, the remaining strains belonged to subclade 1A(△2)and clade 1A. Compared with vaccine strain B/Brisbane/60/2008, the nucleotide homology of circulating strains HA (NA) was 97.62%~98.19% (98.11%~98.78%). The mutations of HA in 1A (△3) B subclade mainly were in 120 loop and 160 loop. All the Yamagata strains circulating in Songjiang district belonged to clade 3. Compared with vaccine strain B/Phuket/3073/2013, the nucleotide homology of HA and NA were 98.71%~99.04% and 98.69%~99.27%, respectively. No amino acid change was found in the antigenic clusters. Neuraminidase inhibition assay showed that the influenza B virus strains were sensitive to both oseltamivir and zanamivir.Conclusions:Inconsistence of the antigenicity between the vaccine strains and the circulating strains during 2017—2020, influenza B virus should be persistently monitored, including the epidemic situation and the etiological characteristics, which might be helpful in vaccine screening and drug development.

B7-H3 is an immune checkpoint molecule overexpressed on the surface of a variety of tumors, and is is an ideal target for tumor immunotherapy. In this study, nitrolated T cell epitope designed in the early stage of the laboratory was used to construct an epitope vaccine that can target immune checkpoint B7-H3. The vaccine can significantly inhibit tumor growth in the CT26 colon cancer model, and has a significant synergistic effect with the PD-L1 protein vaccine. B7-H3 vaccine can increase the proportion of CD4+ T cells in splenic T lymphocytes and the proportion of CD8+ T cells in tumor-infiltrating T lymphocytes, while reducing the proportion of suppressor Treg cells in tumor-infiltrating CD4+ T lymphocytes, which effectively improves tumor immunosuppressive microenvironment. Research results suggest that the B7-H3 epitope vaccine can be used as an effective tumor vaccine candidate molecule.

Using the genetic code extension technology, the immunogenic amino acid, p-nitrophenylalanine, was introduced into the universal T cell epitope and then fused with the fragment of the extracellular region of the immune checkpoint molecular CD47(19-140)to construct a vaccine targeting CD47. The CD47-NitraTh vaccine elicited high titer antibody in BALB/c mice, significantly inhibited CT26 colon cancer cells growth, and increased the ratio of spleen CD4+ T cells and CD8+ T cells. Meanwhile, it promoted the polarization of naï ve T cells to Th1 cells. Notably, CD47-NitraTh not only increased the proportion of tumour-infiltrating lymphocytes but also reduced the proportion of Treg cells in tumour tissues, which means that CD47-NitraTh vaccine can remodel the tumour immunosuppressive microenvironment. The results of this study suggested that CD47-NitraTh can be used as an effective tumour vaccine candidate.