Objective To investigate the clinical effect of lung equivalent uniform dose (LEUD)-based predictive model for radiation pneumonitis (RP) induced by volumetric modulated arc therapy (VMAT) and to determine the optimal a value.Methods A total of 65 patients with primary lung cancer who received VMAT from July 2015 to February 2016 were divided into RP group and non-RP group according to the presence or absence of RP after radiotherapy.Their dose-volume histogram (DVH) data and other data were obtained and analyzed by the self-compiled numerical analysis program.The LEUD values in the two groups were calculated at a=[-50, 50], and then the a value was identified when the relative difference of LEUD between the two groups was maximal.The paired t test was used for analyzing the differences in V5, V20, V30, minimum lethal dose (MLD), and LEUD (aoptimal) between the two groups.A Pearson correlation analysis was used to determine the correlation of Vdose and LEUD (aoptimal) with RP.The logistic regression method was used to establish the predictive model of RP.Results The maximum relative difference in LEUD between RP group and non-RP group was obtained at a=0.3(627.94 cGy vs.510.23 cGy, relative difference[R]=23.07%).R decreased slowly at t=[-50,-5], increased sharply at t=[-5, 0], and reached the maximum value at a=0.3.After a rapid decrease at a=[0.3, 4], R decreased slowly at a=[4, 50].The correlation analysis of the traditional physical volume dose threshold also showed that the LEUD (at a=0.3) was correlated with V5, V10, V20, and MLD (r=0.929, P<0.05).Conclusions For patients receiving VMAT for thoracic cancer, LEUD (at a=0.3) can distinguish between patients with and without RP.Therefore, LEUD is recommended to be<510 cGy.A combination of LEUD and conventional physical dose has a good clinical predictive value for RP under non-uniform irradiation.

Objective:To study the effects of rolling blood pump parameters and blood concentration on hemolysis during extracorporeal circulation.Methods:According to the extracorporeal hemolysis experiment standard, an extracorporeal circulation experimental device was built to analyze the influences of circulation time (0 ~ 90 min), blood flow rate (1~4 L/min), and blood volume fraction (60%, 70%) on the hemolysis of blood samples in the circulatory system. The results of hemolysis were analyzed using first-order linear regression.Results:The longer the blood pump circulation time, the greater the hemolysis rate; the higher the blood flow rate, the greater the hemolysis rate. When the flow rate is 1 and 2 L/min, the hemolysis rate curve has an inflection point that changes with time, i.e. when the circulation time exceeds 30 min, the slope of the hemolysis rate curve suddenly increases. However, when the flow rate is 3 and 4 L/min, the hemolysis mutation phenomenon is not obvious. Compared to the blood sample with blood volume fraction of 70%, a blood sample with a blood volume fraction of 60% is less prone to hemolysis.Conclusions:The longer the blood pump circulation time and the higher the blood flow rate, the more easily the red blood cells are destroyed, i.e. the hemolysis rate is directly proportional to the circulation time and blood flow rate. When the circulation time increases to a certain degree, an inflection point appears in the hemolysis rate curve, and the hemolysis trend will be significantly enhanced.

Objective:To investigate the etiologies and clinical characteristics of bilateral adrenal lesions.Methods:The clinical data of 143 patients with bilateral adrenal lesions hospitalized in the First Affiliated Hospital of Chongqing Medical University from Jan. 2013 to Mar. 2018 were collected and analyzed.Results:140 patients were retained for final analysis. 79 were men, and 61 were women. The age was (51.53±13.93) years. Regarding the etiologies, there were primary aldosteronism ( n=44, 31.43%) , Cushing’s syndrome ( n=27, 19.29%) , non-functional lesions ( n=23, 16.43%) , adrenal tuberculosis ( n=17, 12.14%) , pheochromocytoma ( n=11, 7.86%) , congenital adrenal hyperplasia ( n=5, 3.57%) , adrenal metastases ( n=5, 3.57%) , and adrenal lymphoma ( n=4, 2.86) . These patients were classified into the following groups according to the mass size: ≤2 cm, 2-4 cm and ≥4 cm. The highest proportion of primary aldosteronism (62.79%) , Cushing’s syndrome (46.15%) and pheochromocytoma (31.25%) was observed in the ≤2 cm, 2-4 cm and ≥4 cm groups, respectively. The mass sizes of primary aldosteronism, Cushing’s syndrome and pheochromocytoma were compared, with pheochromocytoma the largest, followed by Cushing’s syndrome, non-functional lesion, and primary aldosteronism. Conclusions:For patients with bilateral adrenal lesions in our hospital, primary aldosteronism and Cushing’s syndrome are more common than non-functional lesion. Mass size is of great value in the diagnosis of endocrinological etiology, as well as distinguishing malignant tumors from the benign ones. The imaging phenotype is helpful to determine tumor types.

Objective To evaluate etoposide,methotrexate and dactinomycin (EMA)/ cyclophosphamide and vincristine (CO) regimen for treatment of ultra high-risk gestational trophoblastic neoplasia (GTN).Methods A total of twenty-four ultra high-risk patients who had International Federation of Gynecology and Obstetrics (FIGO) prognostic scores greater or equal to 12 with liver,brain,or extensive metastases did poorly when treated with primary chemotherapy admitted in Women's Hospital,School of Medicine,Zhejiang University from January 2001 to December 2015.All of the patients were treated by EMA/CO regimen and followed up to death or December 2017.The clinical data of patients were analyzed retrospectively and the efficacy and toxicity of EMA/CO were evaluated.Results All of the cases with ultra high-risk GTN had FIGO prognostic scores ≥12 (ranged 12-18,median 13.0).Twenty patients (83％,20/24) received EMA/CO regimen as primary treatment and 4 patients (17％,4/24) had a history of failed chemotherapy.Seven patients (29％,7/24) had metastasis of liver or brain and 17 patients (71％,20/24)had no metastasis of liver and brain.Twenty-four patients received totally 167 courses of EMA/CO regimen (average 7.0 courses).Sixteen patients achieved complete remission and 8 patients showed drug-resistant.The complete remission rate was 67％ (16/24) and the resistance rate was 33％ (8/24).Of the 16 patients who got complete remission,6 cases were treated with EMA/CO regimen alone,and 10 cases were treated by chemotherapy combined with surgery.For the 8 patients who showed drug-resistant to EMA/CO,5 cases of them received EMA/etoposide and cisplatin (EP) regimen and 3 cases got remission,1 case received methotrexate,dactinomycin and cyclophosphamide (MAC) regimen and got remission,2 cases gave up treatment because of economic factors.The side effects of EMA/CO mainly included Ⅲ-Ⅳ degree neutropenia,anemia and alopecia.The incidence of Ⅲ-Ⅳ degree neutropenia during the treatment of EMA/CO was 21.6％ (36/167),the incidence of anemia was 96.4％ (161/167),and the incidence of alopecia was 60.5％ (101/167).In these 24 ultra high-risk GTN patients,4 patients died during follow-up.In the 20 patients who got complete remission,no recurrence or secondary tumor by chemotherapy were occurred.Conclusion EMA/CO is an effective regimen with manageable toxicity for patients with ultra high-risk GTN.

By reviewing the ancient and modern literature， the name， origin， medicinal parts and other aspects of Linderae Radix in famous classical formulas were systematically sorted out， so as to provide a basis for development of famous classical formulas containing this herb. Linderae Radix was first recorded in Bencao Shiyi in the Tang dynasty under name of Pangqi， and since Rihuazi Bencao of the Five dynasties， all generations of materia medica have used Wuyao as its proper name of the herb. The mainstream source of Linderae Radix used in the past dynasties is dried tuberous roots of Lindera aggregata contained in the 2020 edition of Chinese Pharmacopoeia. The origins of Linderae Radix recorded in the past dynasties are mainly Guangdong， Guangxi， Hunan， Zhejiang， Anhui and others， since the Song dynasty， Tiantai county in Zhejiang province has been regarded as the authentic producing place， in modern times， it is still the authentic place of origin. At harvesting， in ancient times， the harvesting time of the roots was mostly in August， while in modern times， Linderae Radix is mostly harvested in winter and spring or throughout the year， and is dried directly after harvesting or cut thin slices and dried in the place of production. At processing， Linderae Radix was processed by removing the peel and heart， wine roasting， vinegar roasting and other methods in ancient times， and in modern times， it is mostly used in raw form as medicine. In conclusion， it is suggested that the processing method of fresh slicing and drying in the place of origin in the 2020 edition of Chinese Pharmacopoeia should be adopted if Linderae Radix is involved in the development of famous classical formulas.

ObjectiveTo investigate the effects of Shegan Mahuangtang and its pungent and bitter Chinese herbs on the expression of transient receptor potential vanilloid-1 （TRPV1） and bitter taste receptor 14 （TAS2R14） in the lung tissue of the rat model of cold asthma. MethodSeventy SD rats were randomized into 7 groups： normal， model， Shegan Mahuangtang， pungent Chinese herbs， bitter Chinese herbs （6.43 g·kg^-1）， dexamethasone （0.5 g·kg^-1）， and Guilong Kechuanning （10 g·kg^-1）. The rat model of cold asthma was established by intraperitoneal injection and subcutaneous injection of 10% ovalbumin （OVA） and aluminium hydroxide in the limbs， combined with 2% OVA atomization and cold （2-4 ℃） stimulation. The rats were treated with corresponding drugs by gavage and atomization， and the normal and model groups were treated with the same amount of normal saline for 3 weeks. After the last excitation， airway inflammation and cell proliferation were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS）， and Masson staining of the lung tissue. The levels of interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， thymic stromal lymphopoietin （TSLP）， and transforming growth factor-β₁ （TGF-β₁） in the serum were measured by enzyme-linked immunosorbent assay （ELISA）. The expression of TRPV1 and TAS2R14 was detected by immunofluorescence. The expression of TRPV1， TAS2R14， phospholipase Cβ₂ （PLCβ₂）， B-cell lymphoma-2 （Bcl-2）， and α-smooth muscle actin （α-SMA） in the lung tissue was determined by Western blot. ResultCompared with the normal group， the model group showed decreased water intake， food intake， and body weight， increased airway inflammatory cell infiltration， goblet cell proliferation， tissue fibrosis and collagen deposition， elevated levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， upregulated expression of TRPV1， PLCβ₂， and α-SMA， and downregulated expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. Compared with model group， Shecgan Mahuangtang， pungent Chinese herbs， and bitter Chinese herbs increased the water intake， food intake， and body weight， reduced the inflammatory cell infiltration and goblet cell proliferation， alleviated tissue fibrosis and collagen deposition， lowered the levels of IL-5， TNF-α， TSLP， and TGF-β₁ in the serum （P<0.01）， downregulated the expression of TRPV1， PLCβ₂， and α-SMA， and upregulated the expression of TAS2R14 and Bcl-2 （P<0.05， P<0.01）. ConclusionShegan Mahuangtang and its pungent and bitter Chinese herbs can reduce OVA-induced airway inflammation， downregulate the expression of TRPV1， PLCβ₂， and α-SMA， and upregulate the expression of TAS2R14 and Bcl-2 in asthmatic rats. Moreover， bitter Chinese herbs outperformed pungent Chinese herbs， and the combination of them enhanced the therapeutic effect. It is suggested that Shegan Mahuangtang and its pungent and bitter Chinese herbs may ameliorate the OVA-induced airway inflammation by inhibiting TRPV1 and activating TAS2R14.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

ObjectiveTo explore the brain mechanism of repetitive transcranial magnetic stimulation (rTMS) on dysfunction after stroke using functional magnetic resonance imaging (fMRI). MethodsLiteratures about the functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke were retrieved in PubMed, Web of Science, CNKI and Wanfang data from establishment to June 1st, 2021. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature screening, and data extraction were performed by two researchers. ResultsA total of 14 randomized controlled trials were finally enrolled. They were of high or very high quality. They mainly involved the therapeutic effect and imaging mechanisms of rTMS on dysfunction after stroke. ConclusionrTMS could change the excitability of the cerebral cortex and the effective connections between brain regions after stroke, promote the reorganization of brain function, and achieve the recovery of post-stroke dysfunction.

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.

To isolate bone marrow mesenchymal stem cells (BM-MSCs) and establish the model of chronic kidney disease (CKD) of Wuzhishan (WZS) mini-pig, and to study the repairment effect of BM-MSCs on CKD-induced renal fibrosis in vitro.
 Methods: Density gradient method was used to isolate and culture BM-MSCs. The cells were verified by morphology, phenotype, differentiation and so on. The left partial ureteral obstruction (LPUUO) was used to establish the CKD model, which was evaluated by B-ultrasound, single-photon emission computed tomography (SPECT), HE and Masson staining. The cells were divided into 3 groups, the tissue plus BM-MSCs group, the tissue group, and the BM-MSCs group, respectively. Seven days later, the supernatants were collected to observe the changes of hepatocyte growth factor (HGF) cumulative release. HE and Masson staining was used to observe the changes of renal tissue.
 Results: The isolated BM-MSCs possessed the features as follow: fibroblast-like adherent growth; positive in CD29 and CD90 expression while negative in CD45 expression; osteogenic induction and alizarin red staining were positive; alcian blue staining were positive after chondrogenic induction. Twelve weeks after the operation of LPUUO, B-ultrasound showed the thin renal cortical with pelvis effusion; SPETCT showed the left kidney delayed filling and renal impairment. The accumulation of HGF in the tissue plus BM-MSCs group was significantly higher than that in the tissue alone group at the 1st, 5th, 6th, 7th day, respectively (P<0.05). HE staining showed the different degree of renal lesions between the tissue plus BM-MSCs+CKD group and the tissue alone group, which was aggravated with the time going. Masson staining showed that the cumulative optical density of blue-stained collagen fibers in tissue plus BM-MSCs group was significantly lower than that in the tissue group at the 5th to 7th day (P<0.05).
 Conclusion: BM-MSCs from WZS mini-pig can inhibit or delay the progress of CKD-induced renal fibrosis through autocrine HGF in vitro.
Animals ; Autocrine Communication ; physiology ; Bone Marrow Cells ; Cells, Cultured ; Fibrosis ; physiopathology ; prevention & control ; Hepatocyte Growth Factor ; metabolism ; Kidney ; drug effects ; pathology ; physiopathology ; Mesenchymal Stem Cells ; drug effects ; Renal Insufficiency, Chronic ; complications ; physiopathology ; Swine ; Swine, Miniature ; Ureteral Obstruction ; complications