Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

The correspondence between prescription and syndrome is the advantage and characteristic of traditional Chinese medicine(TCM)treatment.However,the pathogenesis of clinical diseases is complex and the condition is changeable,and the clinical application is difficult to achieve the maximum effect under the existing cognition of the correspondence between prescription and syndrome.In this paper,the five categories of physiological characteristics,pathological characteristics,constitution,syndrome,and disease of the longitudinal classification of"TCM state"are introduced into the correspondence of prescription and syndrome.Under the vertical perspective of"TCM state",the theoretical connotation of the correspondence between prescription and syndrome is interpreted as"correspondence between prescription and state",namely correspondence of"prescription-physiological characteristics",correspondence of"prescription-pathological characteristics",correspondence of"prescription-constitution",correspondence of"prescription-syndrome",and correspondence of"prescription-disease".It is hoped to accurately grasp the corresponding connotation of the correspondence between prescription and syndrome,in order to deepen the clinical thinking mode of TCM.

Based on the"You Gu Wu Yun"theory in traditional Chinese medicine(TCM),this paper believes that"Gu"in"You Gu Wu Yun"is extended to"state"from the perspective of"TCM state".In order to avoid the adverse reactions of TCM,the macro,meso,and micro three views should be used together,and macro,meso,and micro parameters should be integrated.We should also carefully identify the physiological characteristics,pathological characteristics,constitution,syndrome,and disease of human body by combining qualitative and quantitative method,highlighting the relationship between the prescription and the"state".The correspondence between prescription and the"state"will reduce the risk of adverse reactions of TCM.In this paper,we hope to focus on the guiding role of the"You Gu Wu Yun"theory in TCM research,to give full play to the characteristics and advantages of TCM,and to dialectically treat the role of TCM.

In the context of the complex and ever-changing spectrum of diseases, the traditional Chinese medicine compatibility of prescription and drugs is no longer able to fully meet the needs of clinical diagnosis and treatment. Therefore, this article is based on the diagnosis and treatment model of the combination of disease, syndrome, and symptom, combined with the development achievements of Western medicine, and explores the principles of formulating traditional prescriptions based on the combination of chief, deputy, assistant, and envoy. This article proposes a formulation principle of composing prescriptions with the diagnosis of syndrome as the chief, the diagnosis of disease as the deputy, the treatment of symptoms as the assistant, and the harmonization of medicine as the envoy. This forms a treatment plan with the core link of syndrome differentiation and treatment, disease differentiation and treatment, symptomatic treatment, detoxification, and efficacy enhancement. The purpose of this article is to address the current clinical challenges such as an increasing disease spectrum and the complexity of syndrome patterns and symptom clusters. It aims to provide new insights into traditional Chinese medicine clinical treatment plans and herbal formulation strategies, with the ultimate goal of improving the clinical effectiveness of traditional Chinese medicine.

Objective:To evaluate the clinical efficacy of Gushen Jianpi Huashi Decoction combined with irbesartan in the treatment of spleen and kidney deficiency syndrome of diabetic nephropathy (DN).Methods:According to random number table method, 97 patients with DN who met the inclusion criteria and from January 2018 to September 2020 were randomly divided into two groups, 48 in the control group and 49 in the study group. The control group took irbesartan on the basis of routine treatment of western medicine, and the study group took Gushen Jianpi Huashi Decoction on the basis of the control group. Both groups were treated for 14 days as a course of treatment, a total of 6 courses of treatment. Traditional Chinese Medicine (TCM) syndrome scores were performed before and after treatment, BUN and SCr levels were detected by automatic biochemical instrument, and serum IL-6, TNF-α, and CRP levels were detected by ELISA. The Urinary microalbumin excretion rate (UAER) was measured by radioimmunoassay, and the clinical efficacy was evaluated and adverse reactions were recorded.Results:The total effective rate was 91.8% (45/49) in the study group and 75.0% (36/48) in the control group, and there was significant difference between the two groups ( χ2=4.99, P=0.025). The scores of TCM syndrome in the study group was significantly lower than that of the control group ( t=29.75, P<0.01). After treatment, the serum BUN [(4.49 ± 0.68) mmol/L vs. (5.16 ± 0.61) mmol/L, t=5.11], SCr [(63.42 ± 4.09) μmol/L vs. (69.01 ± 4.35) μmol/L, t=6.52] and UAER [(72.58 ± 5.88) μg/min vs. (85.63 ± 6.49) μg/min, t=10.44] in the study group were significantly lower than those in the control group ( P<0.01), the serum IL-6, CRP and TNF-α levels in the study group were significantly lower than those in the control group ( t values were 9.44, 7.24 and 18.08, respectively, P<0.01). During the treatment, the incidence of adverse reactions was 14.6% (7/48) in the control group and 16.3% (8/49) in the study group, but there was no significant difference between two groups ( χ2=0.06, P=0.812). Conclusion:The Gushen Jianpi Huashi Decoction combined with irbesartan can improve the renal function of DN patients, reduce the level of inflammatory cytokines and improve the clinical effect.

Objective:To investigate the clinical effect of facial depression correction by using free anterolateral thigh adipofascial flap and human acellular dermal matrix.Methods:Nineteen facial depression patients (3 males and 16 females), age ranges from 16 to 56 years (average age: 29.1±10.37 years), caused by different reasons were selected in this research from Jan. 2008 to Dec. 2020. In the stage I operation, anterolateral thigh adipofascial flap was designed according to facial depression area and harvested to fill in the depression with vascular anastomosis; In the stage II operation, the human acellular dermal matrix was used to fill in the remained depression edge according to facial subunit.Results:All free anterolateral thigh adipofascial flap survived well. All patients revealed fascial subunit tissue atrophy of different degree in infraorbital, nasolabial sulcus and temporal areas which were repaired by using cellular dermal matrix and obtained satisfying effect during 1 to 8 years of follow-up with no obvious rejection. 18 of 19 patients showed flap hypertrophy and corrected by liposuction. All patients recovered well after 1 to 8 years of follow-up.Conclusions:Humana cellular dermal matrix could make up the limitations of treating fascial depression deformity when using anterolateral thigh adipofascial flap. The combination method of above approaches could obtain satisfying clinical effect, which is worthy of clinical promotion.

An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an "all-in-one" vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared

Objective:To evaluate systematically the outcomes of prevention of fragility fracture with alendronate use for 3 to 4 years.Methods:We searched CENTRAL, MEDLINE, EMBASE and CBM for relevant randomized controlled trials published before 16 July, 2020. The quality of included studies was evaluated according to the Cochrane tool for assessing risk of bias. Fix- or random-effects were taken for meta-analysis depending on the magnitude of heterogeneity. Sensitivity analysis was used for high risk studies to assess the robustness of results. The results were reported according to The PRISMA 2009 Check-list.Results:A total of 8 reports from 4 studies were included. Two reports from 2 studies were rated as high-risk while the other 6 reports from the other 2 studies as low-risk. The meta-analyses showed that use of alendronic acid for 3 to 4 years effectively prevented new vertebral fracture ( RR=0.54, 95% CI: 0.44 to 0.66, RD=-0.03), clinical fracture ( RR=0.82, 95% CI: 0.73 to 0.92, RD=-0.03), non-vertebral fracture ( RR=0.84, 95% CI: 0.75 to 0.95, RD=-0.02), clinical vertebral fracture ( RR=0.51, 95% CI: 0.34 to 0.76, RD=-0.01) and hip fracture ( RR=0.56, 95% CI: 0.37 to 0.87, RD=-0.01), but did not prevent wrist fracture ( RR=0.85, 95% CI: 0.67 to 1.09), serious adverse event ( RR=0.95, 95% CI: 0.80 to 1.14) or upper gastrointestinal adverse event ( RR=1.02, 95% CI: 0.96 to 1.07). By the sensitivity analysis of the 6 results from the high-risk reports, the HRs for clinical fracture, non-vertebral fracture, vertebral fracture, hip fracture, wrist fracture, and serious adverse event were, respectively, 0.81, 0.85, 0.49, 0.62, 0.94 and 0.94. Conclusions:Alendronate use for 3 to 4 years can effectively prevent fragility fractures in postmenopausal women with low bone mass or osteoporosis, leading to better prevention effect on vertebral fracture than on non-vertebral fracture.

Objective To analyze the echocardiographic findings , associated anomalies and chromosomal characteristics in fetuses with pulmonary atresia with ventricular septal defect ( PA/VSD ) . Methods T he echocardiographic data and follow‐up materials were retrospectively reviewed in 30 256 fetuses from December 2012 to M arch 2018 in the consultation center of fetal heart disease in maternal‐fetal medicine in Anzhen hospital . Of all the fetuses ,59 cases ( 0 .19% ) had PA/VSD . T he echocardiographic findings ,associated anomalies and chromosomal characteristics were retrospectively analyzed in all the 59 fetuses with PA/VSD . Based on w hether the presence of the native pulmonary arteries and the major aortopulmonary collateral arteries ( M APCAs) or not ,the PA‐VSD was classified into type A ,type B ,and type C . Results A large ventricular defect was demonstrated in five‐chamber view with 61 .7% of the mean ratio of the aortic overriding . O ther fetal echocardiographic features of all the 59 fetuses with PA/VSD included :the right aortic arch ( n ＝19 ) ,reversal flow in the ductus arteriosus ( n ＝40 ) ,M APCAs ( n ＝24) . T he classification of the PA/VSD included :type A ( n ＝35) ,type B ( n ＝5) and type C ( n ＝19) . Associated anomalies :persistent left superior vena cava ( n ＝ 13 ) ,anomalous pulmonary vein connection ( n＝5 ) ,complete atrioventricular septal defect ( n ＝ 5 ) ; single umbilical artery ( n ＝ 3 ) ,right atrial isomerism ( n ＝3) . Of all the 30 cases performed chromosomal test ,3 cases had aneuploidy and 7 cases had microdeletion of chromosome . Conclusions The fetal echocardiographic findings of the PA/VSD are characteristic . For prenatal diagnosis of PA/VSD ,the type of PA/VSD should be defined and chromosomal test should be performed ,w hich can be helpful for prenatal consulting .

Objective Tumor cells are able to support their malignant proliferation by changing metabolic models .Prostate cells rely much on lipid metabolism in which ATP-citrate lyase ( ACLY) plays a very important role .The aim of this research was to study the effects of downregulated ACLY on the cell proliferation , cycle distribution and apoptosis of androgen-independent prostate cancer cells DUl45. Methods DU145 cells were divided into two groups:the cells in experiment group were transfected with the small interfering RNA-mediated knockdown of ACLY , while the cells in control group were transfected with meaningless small interfering RNA.Cell counting Kit test ( CCK-8 ) was applied to detect the effects of the downregulation of ATP citrate lyase on the proliferation of DU145.Flow cytometry instrument was used to analyze the variation of cell cycle distribution and apoptosis rate between groups .Western blot was used to detect the change of intracellular Caspase-3 protein content. Results Western blot showed favorable effects of ACLY interference .Compared with control group , ACLY protein content significantly decreased in experiment group ( P<0.05) ;the acetyl coenzyme A content and the percentage of early apoptosis cells and late apoptosis cells increased significantly [(0.42±1.99) vs (0.79±2.38), (37.10±3.28) vs (6.20±2.88), P<0.05].As to the selec-tive ACLY knockdown in DU145 cells, the proliferation ability in experiment group weakened in comparison with control group , which became more and more apparent as time went on .At 48h and 72h time points, the cell absorbance between two groups at the same time point was of significant difference (P<0.05).As to the interfering ACLY expression in DU145 cells, the percentage of G1 cells in-creased without any statistical significance (P>0.05), while the percentage of G2 cells decreased and the percentage of S cells in-creased with most cell cycle blocking at G 0/G1 stage, which were of significant difference .Meanwhile the expression of apoptosis pro-tein Caspase-3 upregulated significantly . Conclusion ACLY is of vital significance to maintain the malignant proliferation of prostate cancer cells and its downregulation results in the inhibition of cell proliferation and the promotion of cell apoptosis .