Objective: To understand the pathogen spectrum composition of non-bacterial respiratory infections in Pinghu City, Zhejiang Province, so as to provide insights for the prevention and control of respiratory infectious diseases. Methods: A total of 592 throat or nasopharynx swab samples were collected from fever patients in Pinghu First People's Hospital from Jamuary 2021 to November 2022. Multiple real-time fluorescence quantitative polymerase chain reaction was used to detect the nucleic acids of rhinovirus (RhV), respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus (ADV), metapneumovirus (MPV), coronavirus (CoV), Boca virus (Boca), enterovirus (EV), influenza virus (Flu), chlamydia pneumoniae (CP) and mycoplasma pneumoniae (MP). The detection rates of pathogens and mixed infections in different age groups and seasons were analyzed. Results: A total of 212 samples were tested positive for at least one pathogen's nucleic acid from 592 samples, with a total detection rate of 35.81%. The detection rates of RhV (9.80%), PIV (7.26%), Flu (6.76%), RSV (4.39%) and CoV (3.72%) were relatively high. The detection rates were higher among patients at ages of 0 to 2 years and 3 to 17 years than among patients at ages of 18 to 59 years, and in autumn than in spring and winter (all P<0.05). Twenty-three samples were infected by mixed pathogens, accounting for 3.89%. The mixed infections were all detected two pathogens, with PIV, CoV, RhV, and ADV predominant. Conclusions From 2021 to November 2022, the main pathogens of non-bacterial respiratory infections in Pinghu City were RhV, PIV, FLu, RSV and CoV, and there were mixed infections. It is necessary to strengthen the prevention and control of respiratory infection in infants and children.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective: To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. Methods: According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. Results: The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. Conclusion This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

A 22-year-old female has complained of hirsutism, acanthosis nigricans, enlarged clitoris, and menstrual disorders since puberty. Laboratory examinations revealed hyperandrogenemia. Severe insulin resistance and diabetes were found during hospitalization in our hospital. She was diagnosed with type A insulin resistance syndrome finally. After treatment with metformin, the acanthosis nigricans was significantly relieved, blood glucose was controlled satisfactorily, and the menstrual cycle was restored.

Objective:To investigate the clinical characteristics of four McCune-Albright syndrome (MAS) patients associated with growth hormone(GH)-prolactin(PRL) pituitary adenoma, and explore more effective clinical treatment and management methods.Methods:The clinical data of four patients with MAS and GH-PRL pituitary adenoma diagnosed by Peking Union Medical College Hospital were retrospectively analyzed, including clinical manifestations, biochemical parameters, radiographic characteristics, as well as treatment and prognosis. Literature review was also conducted to analyze the efficacy of surgical operations and drug intervention.Results:Clinical characteristics: 3 females and 1 male, all of whom had onset before the age of 7 years. The types of fibrous dysplasia of bone were all polyosseous and involved craniofacial region. There were obvious gigantism/acromegaly manifestations in all cases, 3 cases had evident visual impairment and 1 case with optic chiasm compression. There was no spontaneous or triggered lactation in all 4 patients. Laboratory examination: GH and insulin-like growth factor-Ⅰ(IGF-Ⅰ) levels were significantly increased in 4 patients, GH levels were not inhibited by oral glucose tolerance test (OGTT), PRL levels were over 100 ng/ml, ALP levels were significantly increased in 4 patients, while serum calcium and phosphorus levels were remained normal. Imaging features: All pituitary adenomas in 4 patients were macroadenomas, with unilateral cavernous sinus enclosure in cases 2 and 3, and recurrence of macroadenoma with bilateral cavernous sinus enclosure in case 4 after the first operation. Four cases of skull CT showed multiple FD in craniofacial bone and skull base. Treatment and outcome: All 4 patients underwent pituitary adenoma resection and bisphosphonate therapy, and somatostatin analogues, dopamine receptor agonists and other treatments were selected according to the situation. Two patients with early diagnosis and initial treatment achieved partial remission after treatment, while the other two patients did not.Conclusions:Patients with MAS and GH-PRL pituitary adenoma had earlier onset age and were more likely to suffer from optic nerve damage. Early diagnosis and reasonable surgical treatment may help to improve biochemical indicators (GH, IGF-Ⅰ, and PRL, etc.) rapidly, and combined drug therapy (somatostatin analogues and dopamine receptor agonists) can better maintain or close to normal biochemical indicators, and ultimately improve the prognosis of patients.

Objective　To dissect the clinical and imaging differences between atypical multiple sclerosis and cerebral small vessels diseases.Methods　We presented one case of a hereditary cerebral small vessel disease-autosomal dominant genetic disease combined with subcortical infarction and white matter encephalopathy (CADASIL),which was initially misdiagnosed as multiple sclerosis.Afterwards.We reviewed literature regarding typical images and clinical aspects in multiple sclerosis and cerebral small vessels diseases and discussed the differential diagnosis points.Results　Multiple sclerosis often starts in young adults,with IgG index greater than 0.7,positive oligoclonal band,central venous signs,few microbleeding and asymmetric periventricular white matter lesions on MRI scan.On the contrary,cerebral small vessel diseases often start in old patients with vascular risk factors.MRI scan often shows the lacunar cerebral infarction,microbleeding,brain atrophy and symmetric periventricular white matter hyperintensity.Conclusion　Understanding the differential points between the two diseases may help avoid misdiagnosis and initiate reasonable treatment immediately.

Objective: To explore the correlation between menopausal hormone therapy（MHT）and breast lesions in perimenopausal women,and to provide evidence for safe use of MHT. Methods: The 40-60 year-old women who visited Hangzhou Women's Hospital and met the diagnostic criteria for perimenopausal syndrome were recruited. The intervention group received MHT and was divided into three subgroups according to the MHT regimen：estrogen-progesterone cycle therapy（A）,estrogen-progesterone continuous therapy（B）,estrogen therapy（C）. The control group did not receive MHT. All the patients received regular mammography to quantify and evaluate breast lesions. The generalized estimating equation was used to analyze the changes of breast lesions between different groups. Results: There were 80 cases in the intervention group,with 49 in group A,26 in group B,5 in group C,and 80 cases in the control group. After two years of follow-up,there was no statistically significant differences of time,group and interaction in breast density,volume of breast fibrous tissue and the volume of breast between three intervention groups and the control group（P>0.05）; there was no statistically significant differences of group and interaction in positive rate of calcification and breast mass between the intervention group and the control group（P>0.05）. Conclusion Receiving MHT intervention for two years did not increase the risk of breast lesions.

Objective To investigate the clinical significance of abnormally expressed PD-1 on CD 4+CD 2 8+/-T cells in peripheral blood of patients with systemic lupus erythematosus ( SLE ) . Methods Peripheral blood samples were collected form 50 patients with primary SLE and 40 healthy subjects and used to isolated mononuclear cells. Expression of CD4+CD28-, CD4+CD28+, CD4+CD28+PD-1+and CD4+CD28-PD-1+T cells in peripheral blood samples of the two groups were detected by flow cytometry. Clinical data of SLE patients were collected. Based on SLE disease activity index (SLEDAI), SLE patients were classified into two groups: stable group (SLEDAI<10) and active group (SLEDAI≥10). Based on the condition of renal damage, they were also divided into two groups: lupus nephritis group and non-lupus ne-phritis group. Differences in T cell expression were compared among these groups. Statistical analysis was performed to analyze the relationships of different T cell subsets with laboratory and clinical parameters rela-ting to SLE and SLEDAI. Results The percentages of peripheral CD4+CD28-, CD4+CD28+PD-1+and CD4+CD28-PD-1+T cells of active group were higher than those of stable and healthy control groups ( P<0. 05). Moreover, patients with lupus nephritis had higher percentages of these T cell subsets than those without (P<0. 01). SLE patients who were positive for anti-dsDNA or anti-SmRNP antibody, or had de-creased complement C3, thrombocytopenia or decreased lymphocytes had higher percentages peripheral CD4+CD28-T cells than those in the corresponding negative group. SLE patients who were positive for anti-dsDNA or anti-SmRNP antibody, or had decreased complement C3, complement C4 or lymphocytes showed en-hanced expression of peripheral CD4+CD28+PD-1+T cells as compared with those in the corresponding nega-tive group. SLE patients positive for anti-dsDNA antibody, or with decreased complement C3 or lymphocytes or suffering from alopecia had higher percentages of peripheral CD4+CD28-PD-1+T cell than those in the cor-responding negative group. Differences between different groups were statistically significant (P<0. 05). Conclusion Abnormal expression of CD4+CD28-T cells and PD-1 on CD4+CD28-and CD4+CD28+T cells in peripheral blood of patients with SLE has certain correlation with laboratory parameters and clinical indicators.

Breast cancer is one of the most common malignant tumors in females.Recent years,surgery,chemotherapy as well as other systemic therapy had greatly improved the prognosis of the patients.However,damage of ovarian function by chemotherapy lowered life quality,especially for young females.At present,there are several methods to protect the ovarian function of female patients undergoing chemotherapy,such as administration of a gonadotropin-releasing hormone (GnRH) analogs,ovarian cryopreservation,unfertilized ova cryopreservation,embryo cryopreservation,inhibitors of apoptosis,etc.Each method has its advantage,disadvantage and indications.Issues related to ovarian protection are reviewed here.