Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.
Acrylamides/therapeutic use* ; Adult ; Aged ; Aminoquinolines/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms/drug therapy* ; China ; Humans ; Middle Aged ; Neoplasm Metastasis ; Receptor, ErbB-2 ; Retrospective Studies ; Trastuzumab ; Treatment Outcome

Leukocyte differentiation antigens (LDAs) play important roles in the immune system, by serving as surface markers and participating in multiple biological activities, such as recognizing pathogens, mediating membrane signals, interacting with other cells or systems, and regulating cell differentiation and activation. Data mining is a powerful tool used to identify novel LDAs from whole genome. LRRC25 (leucine rich repeat-containing 25) was predicted to have a role in the function of myeloid cells by a large-scale "omics" data analysis. Further experimental validation showed that LRRC25 is highly expressed in primary myeloid cells, such as granulocytes and monocytes, and lowly/intermediately expressed in B cells, but not in T cells and almost all NK cells. It was down-regulated in multiple acute myeloid leukemia (AML) cell lines and bone marrow cells of AML patients and up-regulated after all-trans retinoic acid (ATRA)-mediated granulocytic differentiation in AML cell lines and acute promyelocytic leukemia (APL; AML-M3, FAB classification) cells. Localization analysis showed that LRRC25 is a type I transmembrane molecule. Although ectopic LRRC25 did not promote spontaneous differentiation of NB4 cells, knockdown of LRRC25 by siRNA or shRNA and knockout of LRRC25 by the CRISPR-Cas9 system attenuated ATRA-induced terminal granulocytic differentiation, and restoration of LRRC25 in knockout cells could rescue ATRA-induced granulocytic differentiation. Therefore, LRRC25, a potential leukocyte differentiation antigen, is a key regulator of ATRA-induced granulocytic differentiation.
Antigens, Differentiation ; immunology ; metabolism ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Granulocytes ; cytology ; drug effects ; immunology ; metabolism ; Humans ; Leukocytes ; cytology ; drug effects ; immunology ; metabolism ; Membrane Proteins ; antagonists & inhibitors ; immunology ; metabolism ; RNA, Small Interfering ; pharmacology ; Tretinoin ; pharmacology

BACKGROUNDDespite the improvement in the health care industry, the rates of undetected, untreated, and uncontrolled hypertension (HTN) are still very high, especially in rural areas of China. The aim of this study was to investigate the efficacy and efficiency of a guideline-based HTN management (novel therapy) in population of rural areas of Guangdong Province.

METHODSTotally, 3113 patients with essential HTN in a rural area of Guangdong Province were enrolled and assigned to two groups, named traditional (n = 372) and novel therapeutic (n = 2741) groups, respectively. Patients in the traditional group were treated routinely, and patients in the novel group were treated in a novel model characterized by regular educational programs for hypertensive populations, close monitoring of blood pressure in combination with finely tuned antihypertensive medications, strict implementation of lifestyle modification and improving medical knowledge and skill of local medical staff efficiently. After 2 years of follow-up, primary endpoints including magnitude of systolic and diastolic blood pressures (SBP and DBP) decrease, treated and controlled rates, as well as secondary endpoints, were evaluated in both groups.

RESULTSInitially, the treated rate was significantly higher in traditional group than that of novel group (71.15% vs. 64.99%, P < 0.05), while the controlled rates were comparable and insignificant difference between baseline BP in both groups (31.07% vs. 26.88%, P > 0.05). Four variables were significantly different, namely smoking rate, daily vegetable consumption (VC), and serum levels of low-density lipoprotein-cholesterol and fasting blood glucose between these two groups. After 2 years of follow-up, decreases in SBP and DBP were more prominent in the novel group (P < 0.001). Treated and controlled rates in both groups were both increased. Nevertheless, in comparison to the traditional group, controlled rate increased more significantly in the novel group (64.31% vs. 37.85%, P < 0.001). Variables indicating lifestyle modification such as high sodium consumption, percentages of alcohol abuse, daily VC were profoundly improved in the novel group.

CONCLUSIONSThe guideline-based HTN management implemented in the current study was beneficial for HTN control in rural areas of Guangdong Province.

Aged ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; China ; Disease Management ; Essential Hypertension ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Rural Population