[The 506th case: fever of unknown origin, negative PET-CT and hemoperitoneum].

A 48-year-old male was admitted to Peking Union Medical College Hospital presented with intermittent fever for two years. The maximum body temperature was 39 ℃, and could spontaneously relieve. The efficacy of antibacterial treatment was poor. He had no other symptoms and positive signs. He had a significant weight loss, and the serum lactate dehydrogenase increased significantly. It was highly alert to be lymphoma, but bone marrow smear and pathology, and PET-CT had not shown obvious abnormalities. Considering high inflammatory indicators, increased ferritin and large spleen, the patient had high inflammatory status, and was treated with methylprednisolone. Then the patient's body temperature was normal, but the platelet decreased to 33×109/L. During hospitalization, he had suddenly hemoperitoneum and hemorrhagic shock. He was found spontaneous spleen rupture without obvious triggers, and underwent emergency splenectomy. The pathological diagnosis of spleen was diffuse large B-cell lymphoma.

[Regulative effects of endogenous sulfur dioxide on oxidant stress in myocardium of rat with sepsis].

OBJECTIVE: To explore the modulating effect of endogenous sulfur dioxide (SO2) on the ba-lance of oxidation/reduction in the cecal-ligation-and-puncture-induced septic rat myocardium. METHODS: Forty male Sprague Dawley rats were randomized into control group, SO2group, sepsis group and sepsis + SO2group. The levels of procalcitonin (PCT), creatine kinase isoenzyme (CK-MB), cardiac troponin Ⅰ (cTn Ⅰ) and fatty acid binding protein (FABP) in plasma in each group of the rats were measured; The level of hydrogen peroxide (H2O2), level of nitric oxide (NO), activity of myeloperoxidase (MPO), activity of hydroxyl free radical (·OH) and level of malondialdehyde (MDA) in myocardial tissue were measured; Total antioxidant capacity (T-AOC), activity of catalase (CAT), level of cytochrome oxidase (CO), level of glutathione (GSH), level of glutathione oxidase (GSH-px) and activity of superoxide dismutase (SOD) in myocardial tissue were measured. RESULTS: The level of PCT in plasma in the rats with sepsis increased from (0.93±0.26) µg/L to (2.45±0.52) µg/L (P < 0.01), and decreased to (1.58±0.36) µg/L after the intervention of sulfur dioxide donor (P < 0.01). In sepsis, the plasma CK-MB, cTn Ⅰ and FABP levels in the rats increased respectively from (14.46±6.48) µg/L, (151.25±30.14) ng/L and (2.72±0.65) µg/L to (23.72±7.72) µg/L, (272.78±52.70) ng/L and (5.22±1.01) µg/L (P all < 0.01), and decreased to (16.74±3.63) µg/L, (184.86±37.72) µg/L and (3.31±0.84) µg/L (all P < 0.05) after the intervention of sulfur dioxide donor. The level of H2O2, level of NO, activity of MPO, activity of ·OH and level of MDA in myocardial tissue in the rats with sepsis increased respectively from (67.26±8.77) mmol/g, (38.39±6.93) µmol/g, (358.25±68.12) U/g, (648.42±93.69) U/ mg and (4.55±0.96) µmol/g to (111.45±17.35) mmol/g, (51.04±5.91) µmol/g, (465.88±76.76) U/g, (873.75±123.47) U/mg and (7.25±0.86) µmol/g (all P < 0.01), and decreased respectively to (75.99±10.52) mmol/g, (39.39±7.80) µmol/g, (393.17±51.5) U/g, (710.54±106.33) U/mg and (5.16±0.65) µmol/g after the intervention of the sulfur dioxide donor (all P < 0.05). The activity of T-AOC, activity of CAT, level of CO, level of GSH, level of GSH-px and activity of SOD in myocardial tissue in the rats with sepsis increased respectively from (2.07±0.37) U/mg, (169.25±36.86) U/g, (1.35±0.32) µmol/g, (103.51±16.62) µmol/g, (38.40±7.97) µmol/g and (38.50±8.30) U/mg to (1.42±0.39) U/mg, (98.44±26.56) U/g, (0.96±0.21) µmol/g, (68.05±7.35) µmol/ g, (23.83±5.04) µmol/g and (23.11±4.63) U/mg (P all < 0.01), and increased respectively to (1.83±0.37) U/mg, (146.14±31.63) U/g, (1.28±0.20) µmol/g, (92.10±11.84) µmol/g, (37.16±3.01) µmol/g and (37.29±2.62) U/mg (P all < 0.05) after the intervention of the sulfur dioxide donor. CONCLUSION: Endogenous SO2 can protect rat myocardium in sepsis by modulating the ba-lance of oxidation and reduction.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

[Perspectives on recent monkeypox outbreak in non-endemic areas].

Monkeypox is a rare infectious disease caused by the monkeypox virus, which used to occur endemically in central and western Africa. As of 25th May, a total of 219 recently confirmed cases of monkeypox have been reported from 19 non-endemic countries. This outbreak unusually takes place in non-endemic areas for monkeypox virus and has exhibited features of high risk of human-to-human transmission. Onset of multiple human monkeypox cases may be related to the decreased level of herd cross-immunity after the cessation of smallpox vaccination. Moreover, behavioral patterns in specific populations may account for the human-to-human transmission in this outbreak. Currently, possibility of global epidemic of monkeypox is extremely low, but China should be cautious about risks of importation of monkeypox cases. The key to prevention and control is to establish a surveillance system to identify suspicious cases and close contacts as soon as possible.

[Investigation and analysis of the implementation status of "Diagnosis and therapy guideline of preterm birth (2014)"].

Objective: To understand the actual situation of the implementation of "Diagnosis and therapy guideline of preterm birth（2014）", "Guideline" for short, by front-line obstetricians, and to provide reference for the further update and supplement of the "Guideline". Methods: This study designed a structured questionnaire for the prominent problems in the prevention and treatment of preterm birth, which was determined by the expert team drafting the "Guideline". In October to November 2021, a cross-sectional survey was conducted among obstetricians, including members of the Perinatal Medicine Branch of Jiangsu Medical Association and the Obstetrics Subgroup,Chinese society of Obstetrics and Gynecology, Chinese Medical Association, on the implementation status of the "Guideline". The recommendations of the "Guideline" were used as standard answers to determine the implementation rate. A total of 328 valid questionnaires were collected. The total score of the questionnaire was 12 points. The questionnaire was divided into low executive ability group (<7 points) and high executive ability group (≥7 points) with a score of 7 as the threshold value, and the differences in baseline information such as hospital grade and professional title between the two groups were compared. Results: The score of 328 obstetricians was (7.6±1.6) points, including 250 (76.2%, 250/328) in the high execution group and 78 (23.8%, 78/328) in the low execution group. The execution rates of "the use of uterine contraction inhibitors for short courses"[97.0% (318/328)], "late umbilical cord breakage after birth of premature infants"[87.8% (288/328)] and "should preterm patients with intact membranes be treated with antibiotics"[86.6% (284/328)] were all over 80%, indicating good implementation. Multiple logistic regression analysis showed that hospital grade and professional title were independent factors influencing the performance of the "Guideline"(all P<0.05), and secondary hospitals had lower scores and worse execution than tertiary hospitals (OR=0.42, 95%CI: 0.23-0.77; P=0.005). Senior titles had higher scores and better execution than junior titles (OR=5.33, 95%CI: 2.35-12.07; P<0.001). When answering the question "gestational week at which premature infants could survive in your hospital", only 3.4% (11/328) answered 22 weeks, and 44.5% (146/328) answered 28 weeks, accounted for the highest proportion. The gestational week of surviving premature infants in tertiary hospitals was earlier than that in secondary hospitals (P<0.05). The gestational week of surviving premature infants answered by senior titles was earlier than that of junior titles (P<0.05). Conclusions: Obstetricians generally have a good implementation of the "Guideline", and their understanding of some recommended clauses in the guidelines needs to be improved. In the future, training of primary hospitals and physicians with junior titles should be strengthened.

[Clinical features and influencing factors of long-term prognosis in patients with tuberculous meningitis].

Objective: To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM. Methods: Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression. Results: A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly (OR=1.06, P=0.048 ) , hyponatremia(OR=0.81,P=0.020), high protein level in cerebrospinal fluid (CSF) (OR=3.32,P=0.033), cerebral infarction(OR=10.50,P=0.040) and hydrocephalus(OR=8.51,P=0.049) were associated with poor prognosis in TBM patients. Conclusions: The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

[The 485th case: fever of undetermined origin and hypoxemia].

A 49-year-old male was admitted to Peking Union Medical College Hospital presented with fever for more than half a year. The patient was diagnosed as Sjogren's syndrome at local hospital. After oral prednisone 60 mg per day was given, the fever alleviated, but recurred after prednisone tapered to 40 mg/d. Both blood culture and stool culture were positive for Salmonella enteritidis. Antibiotics including ceftazidime, ceftriaxone, cilastatin-imipenem were sequentially administrated for 4 weeks, yet not effective. Although there were not respiratory symptoms or certain abnormalities on high-resolution chest CT, arterial blood gas indicated hypoxemia. Serum lactate dehydrogenase and ß2 micro-globulin were elevated, and the lung function test demonstrated significant impairment of diffusion function. Positron emission tomography-computed tomography (PET/CT)scan suggested that high fluorodeoxyglucose uptake was diffusely seen in both lungs. The patient was finally diagnosed as pulmonary intravascular large B-cell lymphoma (IVLBCL) by transbronchial lung biopsy. This case aims to emphasize the differentiation diagnoses of pulmonary intravascular lymphoma from common situations.

Multidisciplinary collaborative integrated management of increasingly prominent HIV complications in the post-cART era.

OBJECTIVES: With the prolonged survival time of AIDS patients, complications of various systems and organs of HIV infection are increasingly prominent. These diseases have become the major factors influencing the quality of life and prognosis of HIV-infected persons, and multidisciplinary cooperation treatment is urgently needed. METHODS: The Chinese HIV/AIDS Clinical Trial Network has conducted a series of multicentre clinical cohort studies over the past 16 years, in which studies related to people living with HIV systemic complications. Based on the results of previous studies, this review establishes the complications of Chinese people living with HIV after long-term cART. RESULTS: HIV's direct damage to human cells, chronic abnormal inflammatory activation after HIV infection, long-term drug side effects caused by cART and persistent reservoirs cause systemic complications in people living with HIV. We summarised the clinical characteristics of the complications of HIV infection in China from the aspects of the liver, cardiovascular, the nervous system, the kidney, bone metabolism, blood glucose, and lipid metabolism. CONCLUSIONS: The management of the complications of HIV infection is a major link in improving the survival treatment and prognosis of patients in the future. The joint participation of doctors from different departments of general hospitals in the management of comorbidities is the main theme for future improvement of quality of life and prognosis for people living with HIV.

[The 481st case: fever, rash, and cough].

Talaromyces Marneffei infection is rarely reported in patients with chronic active Epstein-Barr virus (EBV) infection. We reported an old man with chronic fever, pleomorphic rash, cough, EBV viraemia, and secondary hemophagocytic syndrome. Repeated histological biopsy and culture of skin lesions revealed Talaromyces Marneffei. This patient was diagnosed as chronic active EBV infection, and Talaromyces Marneffei infection. After treated with glucocorticoid steroids and anti-fungal therapy, the patient finally recovered. EBV infection is usually seen in immune compromised patients, who are susceptible to opportunistic pathogens rarely as Talaromyces Marneffei in this case.

[Clinical and coagulation characteristics in 7 patients with critical COVID-2019 pneumonia and acro-ischemia].

Objective: To investigate the clinical and coagulation characteristics in patients with critical Coronavirus disease 2019 (COVID-19) and acro-ischemia. Methods: The retrospective study included 7 critical COVID-19 patients with acro-ischemia in an intensive care unit (ICU) in Wuhan, from Feb 4 to Feb 15, 2020. The clinical and laboratory data before and during the ICU stay were analyzed. Results: The median age of 7 patients was 59 years and 4 of them were men. Three patients were associated with underlying comorbidities. Fever, cough, dyspnea and diarrhea were common clinical symptoms. All patients had acro-ischemia presentations including finger/toe cyanosis, skin bulla and dry gangrene. D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients. Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation. Four patients were diagnosed with disseminated intravascular coagulation (DIC) . Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms. Five patients died finally and the median time from acro-ischemia to death was 12 days. Conclusions: Coagulation parameters should be monitored closely in critical COVID-2019 patients. The timing and protocol of anticoagulation therapy are still under investigation based on more clinical data.

[The differential diagnosis for novel coronavirus pneumonia and similar lung diseases in general hospitals].

Novel coronavirus pneumonia was a novel coronavirus infection that has dominated pulmonary infection since December 2019. The main manifestations were fever, dry cough, shortness of breath, normal or leukopenia in peripheral blood and changes in chest CT and in severe cases, multiple organ failure might occur. The National Health Commission, PRC has revised the consensus on diagnosis and treatment seven times in a short period of time, indicating the growing understanding of the disease. Patients with novel coronavirus pneumonia usually had history of travelling or living in the epidemic area including Wuhan within 14 days before onset, or have been exposed to patients who had fever or respiratory symptoms from the epidemic area, or had clustering diseases. However, novel coronavirus pneumonia was becoming more and more blurred after vanishing epidemic. The diagnosis and differential diagnosis of novel coronavirus pneumonia were challenges not only because of large number of tourists increasing dramatically after the relieving of epidemic, but also patients with other diseases from different areas to search for medical care. In this article, the clinical and chest imaging features of the novel coronavirus pneumonia were reviewed and compared with other infections and non-infectious diffuse pulmonary diseases. We try to find the similarities and differences among them, and to identify clues to the diagnosis of novel coronavirus pneumonia, so as to ensure accurate diagnosis and treatment.