Objective To study whether post-operative radiotherapy is necessary for patients with early breast cancer after radical mastectomy. Methods In 1998, 270 early breast cancer patients with 0 -3 pathologically confirmed positive axillary lymph nodes after radical mastectomy were retrospectively ana-lyzed. There were 156 patients with negative lymph node and 114 with 1 -3 positive lymph nodes. The prog-nostic index (PI) was defined as the sum of scores of the tumor size, number of positive axillary lymph nodes, receptor status, surgical margin status, lymphatic thrombi status, pathological grading and age. The PI≥ 4 was considered as high-risk, and PI <4 as the low-risk. Numerical variables were compared using t test and categorical variables were compared using chi-square test. Kaplan-Meier method was used to calcu-late the survival rates, and the Log-rank test was used for the comparison of the survival curves between dif-ferent groups. Results Of the patients with lymph node negative and 1 - 3 positive, the survival rates were 75.0% and 63.2% (χ~2 = 4.40 ,P =0.036), respectively. The corresponding disease-free survival rate, lo-cal recurrence rate, distant metastasis rate were 71.2% and 9.6% (χ~2 = 3.90, P = 0.048), 7.7% and 16.7%(χ~2 =5.22,P=0.022),12.8% and 21.1%(χ~2=3.27,P=0.070), respectively. The mean dis-ease-free survival time of the two groups was 97.03 ± 2.53 months and 87.01 ± 3.80 months, respectively. In the high-risk group, the 10-year survival rates of patients with and without radiotherapy were 72% and 56% (χ~2 = 4.07, P = 0.044), the local recurrence rates were 5% and 24% (χ~2= 11.16, P = 0. 001), and the distant metastasis rates were 16% and 26% (χ~2= 2.18 ,P = 0. 140). In the low-risk group, the survival rate of patients with and without radiotherapy were 81% and 71% (χ~2 = 1.57 ,P = 0.210), the local recur-rence rates were both 11% (χ~2=0.01 ,P=0.975), and the distant metastasis rates were both 13% (χ~2 = 0.00,P = 1. 000). Conclusions Early breast cancer patients with 1 -3 positive axiilary lymph nodes should receive post-operative radiotherapy after radical mastectomy. The prognostic index may decrease the chance of unnecessary radiation by distinguishing the patients under low risk of recurrence from those under high risk.

Objective: To discuss whether T_2 breast cancer patients with 1-3 positive axillary lymph nodes after radical mastectomy need radiotherapy, and to determine the corresponding target region. Methods: We retrospectively analyzed 103 breast cancer patients treated in our hospital between 1997 and 1998. All pa-tients underwent radical mastectomy. Of these patients, 44 did not receive irradiation, 59 received irradiation to the internal mammary chain and supraclavicular area. All patients had no intumescent axillary lymph nodes or distant metastasis before radical mastectomy. T-test was used to analyze quantitative data, and ANOVA was used to analyze numerical data. Kaplan-Meier method and Log rank test were employed to calculate and compare the survival rate. Results: The 10-year survival rate was 56.8% in the non-irradiation group and 72.9% in the irradiation group (X~2=2.805, P=0.094). The 10-year disease free survival rate was 50.0% in the non-irradiation group and 64.4% in the irradiation group (X~2=4.063, P=0.044). The 10-year local recurrence rate was 27.3% in the non-irradiation and 10.2% in the irradiation group (X~2=5.112, P=0.035). The 10-year met-astatic rate was 43.2% in the non-irradiation group and 22.0% in the irradiation group (X~2=5.263, P=0.031).The 10-year chest wall recurrence rate in all patients was 7.8%. No patients had recurrence in the internal mammary chain area. Irradiation in the internal mammary chain area was useless and could not increase sur-vival rate and disease free survival rate. Irradiation in the internal mammary chain area was not helpful for re-ducing local recurrence rate or distant metastatic rate. Conclusion: Radiation therapy can reduce local recur-rence rate and metastatic rate in T_2 breast cancer patients with one to three positive axillary lymph nodes, and can increase survival rate and disease free survival rate. Recurrence in the internal mammary chain area is rare. Therefore, it is not necessary to irradiate the internal mammary chain area. We suggest that T_2 breast cancer patients with 1-3 positive axillary lymph nodes after radical mastectomy should have irradiation to the chest wall and supraclavicular area.

Objective To investigate the distribution of genotypes in chronic HBV infection (CHB) and acute HBV infection (AHB) patients in Shanghai. Methods Sixty-two patients with AHB and 73 patients with CHB admitted to ('hanghai Hospital of Shanghai between 2003 and 2007 were studied. Viral genotypes of all the patients were determined by direct gene sequencing.Meanwhile, epidemiological, clinical and biochemical parameters of all patients were collected. Mean values of different groups were compared by t test while frequency was compared by chi square test. Results The major prevalent genotypes in both AHB and CHB patients were genotype B and C (48.4% vs 51.6% in AHB patients and 26.0% vs 74.0% in CHB patients). The proportion of genotype B was higher in AHB patients compared to CHB patients (P= 0.02). Epidemiological factors and clinical outcomes were not statistically different among patients with different viral genotypes. The proportion of genotype C was much higher in CHB patients compared to AHB patients (P=0.006). The main transmission route of AHB was heterosexual interaction which was 18 out of 62 (29.0%), but in CHB patients, it was prenatal transmission which was 38 out of 73 (52.1%). Conclusions In shanghai, the main HBV genotypes in both AHB and CHB patients are genotype B and C. The proportion of genotype B is relatively high in AHB patients while proportion of genotype C is more common in CHB patients. There is no significant relationship between genotypes and the clinical outcomes of AI-IB patients.

Objective To analyze the prognostic value of age in patients with early stage breast cancer. Methods The clinical characteristics of 1030 patients with early stage breast cancer (the number of positive axillary lymph nodes was less than 3) were retrospectively reviewed. Of all the patients, 468(stage Ⅰ, n = 227; and stage Ⅱ , n = 241) received breast conserving surgery (BCS) and 562 (stage Ⅰ, n =184; and stage Ⅱ, n= 378) received modified mastectomy. Patients were divided into young-age group (≤35,136 patients), middle-age group (> 35-≤60,738 patients) and old-age group (> 60,156 patients).The number of patients without postoperative radiation therapy after BCS is 16, 60 and 39 in the three groups, respectively. Two-dimensional conventional fractionated radiotherapy was administered. The prognostic value of the tumor size, status of axillary lymph nodes or hormonal receptors, postoperative radiation therapy were analyzed. Results The follow-up rate was 97.86%. Of 795 patients followed up more than 5 years, 110,569 and 116 patients were devided into the three groups, respectively. There were 40, 202 and 87 patients without radiation therapy in the three groups. The 5-year recurrence rates of the three groups were 6. 2%, 8. 7% and 10. 4% (χ2 = 1.14, P= 0.567). The 5-year distant metastasis rates were4.3% , 9.5 % and2. 5% (χ2 = 5.31 , P = 0. 070) . The5 - year survival rates were9l. 2% , 92. 6%and 82. 1% (χ2 = 6. 83, P = 0.033). The young-age group had more tumors smaller than 2. 0 cm (65.4%), less positive axillary lymph nodes (13.2%), poorer differential tumor and less positive hormone acceptors (48.0%). Of patients with tumor larger than 2. 0 cm who had no radiotherapy after BCS, the 5-year survival rates were 94%, 87% and 71% (χ2= 20.69, P= 0.000) in the three groups. The corresponding recurrence rates were 23%, 18% ,7%, (χ2 = 9. 97, P = 0. 007), and distant metastasis rates were23%, 25% and 10% (χ2 =8.51, P=0. 014). Conclusions The age is an important prognostic factor in patients with early stage breast cancer undergoing BCS, but not in those undergoing modified mastectomy.

The identification of pathogenic antigens in membranous nephropathy (MN) is a hot topic in the research field of kidney diseases. In recent years, the widespread application of mass spectrometry has brought a breakthrough in the identification of MN-pathogenic antigens. As the antigen spectrum continues to be refined, the diagnosis of MN has evolved from morphological level to molecular level. This article reviewed the research progress of currently identified antigens of MN, such as phospholipase A2 receptor (a major pathogenic antigen of primary MN), thrombospondin type 1 domain-containing 7A (a potential tumor-associated antigen), neural epidermal growth factor-like protein 1 (an antigen associated with various secondary factors), semaphorin 3B (an antigen specific to pediatric MN) and so on, and the pathogenic mechanisms and clinical significance of these antigens.

Objective:To analyze functional changes in macrophages in mouse models of vulvovaginal candidiasis (VVC) by modulating indoleamine 2,3-dioxygenase 1 (IDO1) .Methods:Forty specific-pathogen-free female ICR mice were randomly divided into 4 groups using a complete randomization method: a blank group, a VVC model group, a VVC model + 1-methyltryptophan (1-MT) group (referred to as the 1-MT group), a VVC model + interferon-γ (IFN-γ) group (referred to as the IFN-γ group), with 10 mice in each group. Except for the blank group, all the mice were injected subcutaneously with estradiol benzoate oil solution in the abdomen every other day for 6 days prior to modeling to induce pseudoestrus; after successful induction of pseudoestrus, the mice were inoculated vaginally with Candida albicans suspensions at a concentration of 2 × 10 9 CFU/ml once a day for 5 days to establish VVC mouse models, and subcutaneous injections of estradiol benzoate oil solution were continued simultaneously to maintain the pseudoestrus state; 1 day before inoculation with fungal suspensions, mice in the 1-MT group and IFN-γ group were pretreated with 1-MT and IFN-γ respectively, followed by once-daily same intervention for 6 consecutive days; mice in the blank group and VVC model group were intraperitoneally injected with physiological saline solution once a day for 6 consecutive days. On the 5th day of modeling, vaginal conditions in mice were observed and vaginal symptoms were scored; the vaginal lavage fluid was collected for smear microscopy and fungal colony counting; then, the mice were sacrificed, the vaginal tissues were collected and subjected to hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining, and the expression of IDO1 and the macrophage surface marker F4/80 was determined in the vaginal tissues by an immunofluorescence method; real-time fluorescence-based quantitative PCR (qPCR) was performed to determine mRNA expression levels of IDO1, inducible nitric oxide synthase (iNOS), and arginase 1 (Arg-1) in the vaginal tissues, and Western blot analysis to determine the IDO1 protein expression in the vaginal tissues. One-way analysis of variance was used to analyze the differences in indices among groups, and Tukey test was used for multiple comparisons. Results:Smear microscopic examination of the vaginal lavage fluid on the 5th day of modeling showed elongated hyphae with a few spores in the VVC model group, a large number of elongated hyphae aggregating in clusters with surrounding spores in the 1-MT group, and a few thin and short hyphae with a large number of spores in the IFN-γ group. Compared with the VVC model group (360.0 ± 15.9), the fungal colony counts in the vaginal lavage fluid significantly increased in the 1-MT group (523.7 ± 67.7, P = 0.002), but significantly decreased in the IFN-γ group (258.3 ± 27.57, P = 0.026). HE staining and PAS staining showed small abscess formation in the epidermis and predominant infiltration of neutrophils throughout the epidermal and dermal layers with a large number of spores and a few hyphae in the VVC model group; thickened epidermis and diffuse inflammatory infiltration predominated by neutrophils in the dermis were seen in the 1-MT group, with a large number of hyphae and spores aggregating into clusters, which were predominated by hyphae; in the IFN-γ group, spores aggregated in the epidermis without obvious hyphae, and a small amount of inflammatory cells predominated by neutrophils infiltrated the dermis. Immunofluorescence assay revealed that the relative fluorescence intensities of IDO1 and F4/80 were highest in the IFN-γ group and the 1-MT group, respectively. Western blot analysis revealed that the IDO1 protein expression in the VVC model group was significantly higher than that in the blank group ( P < 0.001) and the 1-MT group ( P < 0.05), but significantly lower than that in the IFN-γ group ( P < 0.05). qPCR showed that iNOS mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.01), and increased in the IFN-γ group compared with the blank group, VVC model group and 1-MT group (all P < 0.001); Arg-1 mRNA expression significantly increased in the VVC model group compared with the blank group ( P < 0.001) and IFN-γ group ( P < 0.01), and increased in the 1-MT group compared with the blank group, VVC model group, and IFN-γ group (all P < 0.001) . Conclusion:In the VVC mouse models, upregulation of IDO1 may cause macrophage polarization toward the M1 phenotype, and inhibition of IDO1 may cause increased macrophage recruitment and exacerbate the inflammatory response.

Objective To report the spontaneous remission and induced remission of phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) in adults,as well as to explore the potential prognostic factors.Methods A total of 120 patients with IMN in Huashan Hospital during 2012 and 2017 were enrolled and their clinical data were collected.Results PLA2R-associated IMN patients accounted for 89.2％ of the IMN patients.Spontaneous remission occurred in 35.5％ of PLA2R-associated IMN patients.The patients with higher serum albumin and lower level of PLA2R antibody were more likely to achieve spontaneous remission (both P ＜ 0.05).Multivariate logistic regression analysis showed that male was an independent risk factor for spontaneous remission in PLA2R-associated IMN patients (OR=0.060,95％CI 0.007-0.493,P=0.009),while higher serum albumin at baseline (OR=1.480,95％ CI 1.144-1.932,P=0.004) and the improvement of serum albumin after 3 months' non-immunosuppressive treatment (OR=2.040,95％CI 1.322-3.151,P=0.001) were independent protective factors for spontaneous remission.About 42.1％ PLA2R-associated IMN patients had received immunosuppressive therapy,with induced remission rate being 70.7％.High serum albumin before treatment was an independent protective factor for induced remission (OR=1.268,95％ CI 1.014-1.585,P=0.038).Conclusions PLA2R-associated IMN accounts for most of the IMN patients,with a spontaneous remission rate of 35.5％,during the follow-up period,which is even higher in patients with higher baseline serum albumin and lower PLA2R antibody titer.Induced remission rate is 70.7％ in patients in need of immunosuppresants.The serum albumin level may be helpful in predicting spontaneous remission and response to immunosuppressive therapy.

Objective:To investigate the effect of macrophage-derived exosomes on the morphological transformation of Candida albicans (CA), and to explore the underlying mechanisms.Methods:In vitro cultured human acute monocytic leukemia cell line THP-1 was induced and differentiated into M0 macrophages using the phorbol ester PMA. CA was activated and prepared as the fungal suspension. M0 macrophages were infected with the CA suspension, and the process of cell phagocytosis was observed under a high-content imaging analysis system. M0 macrophage-derived exosomes (exosome group) and CA-infected M0 macrophage-derived exosomes (CA exosome group) were extracted by differential centrifugation; transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis were performed to identify and compare exosomes in the two groups. The exosomes from the two groups were separately co-cultured with CA (exosome-treated group and CA exosome-treated group), and independently cultured CA served as the blank control group; the morphological changes of CA were observed under an inverted microscope, the intracellular cyclic adenosine monophosphate (cAMP) contents were detected by the enzyme-linked immunosorbent assay (ELISA), and the expression levels of cAMP-related genes, RAS1 and CDC35 (also known as Cyr1), were detected by real-time quantitative PCR (RT-qPCR) . Results:Western blot analysis showed that exosomes from the exosome group and CA exosome group both expressed the tumor susceptibility gene 101 protein (TSG101, an exosome marker), and did not express calnexin (a negative marker) ; transmission electron microscopy and nanoparticle tracking analysis showed no significant differences in the morphology or size of the exosomes between the two groups. Compared with the blank control group, the exosome-treated group and CA exosome-treated group both showed obvious inhibition of the yeast-to-mycelial phase transition of CA, with a noticeable reduction in the length of the hyphae under the inverted microscope. ELISA revealed that the intracellular cAMP content in CA significantly decreased in the exosome-treated group and CA exosome-treated group (16.70 ± 0.84 pmol/ml, 16.82 ± 0.87 pmol/ml, respectively) compared with the blank control group (21.82 ± 1.08 pmol/ml; t = 6.45, 6.23, respectively, both P = 0.003). RT-qPCR revealed that the expression of the cAMP-related genes, RAS1 and CDC35, was down-regulated in the exosome-treated group and CA exosome-treated group compared with the blank control group (all P < 0.01), and the RAS1 mRNA expression was significantly lower in the CA exosome-treated group than in the exosome-treated group ( t = 7.43, P = 0.002) . Conclusion:Both M0 macrophage-derived exosomes and CA-infected M0 macrophage-derived exosomes could effectively inhibit the mycelial growth of CA, and the latter one exhibited a stronger inhibitory effect, possibly by down-regulating cAMP in the cAMP/protein kinase A pathway.

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.