Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Genetic risk factors have been shown to contribute to the development of sexual dysfunction. However, the role of methylenetetrahydrofolate reductase (MTHFR) gene variants in the risk of erectile dysfunction (ED) remains unclear. In this study, we recruited 1254 participants who underwent ED assessed by the International Index of Erectile Function-5. The MTHFR c.677C>T variant was also measured by fluorescence polymerase chain reaction (PCR). No significant difference in the genotypic frequency of the MTHFR C677T polymorphism (CC, CT, and TT) was observed between men from the ED and non-ED groups. In addition, on binary logistic regression analysis, both crude and adjusted models showed that the risk of ED was not significantly associated with the C677T polymorphism. Interestingly, a significantly higher frequency of the 677TT polymorphism was found in severe and moderate ED (P = 0.02). The positive correlation between the MTHFR 677TT polymorphism and severe ED was confirmed by logistic regression analysis, even after adjusting for potential confounders (odds ratio [OR] = 2.46, 95% confidence interval [CI]: 1.15-5.50, P = 0.02). These findings suggest a positive correlation between the MTHFR 677TT polymorphism and the risk of severe ED. Identification of MTHFR gene polymorphisms may provide complementary information for ED patients during routine clinical diagnosis.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

Osteocalcin (OCN) regulates the physiological structure and function of various peripheral tissues and organs, and plays a central regulatory role, which is tightly associated with higher-level cognitive functions such as learning and memory. Studies have shown that OCN can enter the central nervous system through the blood-brain barrier and bind to GPR158 and GPR37, members of the G protein-coupled receptor (GPCR) family on the membrane of neurons or glial cells, activate or inhibit relevant intracellular signalling pathways, and then change the physiological activities of neurons or glial cells. In the brain, the role of OCN mainly includes regulating the synthesis and release of neurotransmitters such as serotonin, dopamine, norepinephrine and γ-aminobutyric acid, increasing the expression of brain-derived neurotrophic factor, promoting hippocampal neurogenesis, enhancing hippocampal neuron autophagy and maintaining myelin homeostasis, among others. Furthermore, OCN can also be involved in the regulation of the pathophysiological process of multiple neurodegenerative diseases. In Alzheimer's disease (AD), OCN treatment reduces β-amyloid protein (Aβ) deposition and Aβ-induced cytotoxicity in part, thereby improving learning and memory deficits; in Parkinson's disease (PD), OCN treatment inhibits the loss of substantia nigra and striatum dopaminergic neurons, increases the content of tyrosine hydroxylase and decreases neuroinflammation, thereby alleviating motor dysfunction. By analyzing the structure and function of GPR158 and GPR37, analyzing the role of OCN in the brain and its biological mechanism, and exploring the effect of OCN on neurodegenerative diseases such as AD and PD, this paper aims to provide a basis for further screening new targets to promote brain health.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective: To observe the effect of Jiawei Bushen Huoxuetang on osteoporotic vertebral compression fractures (OVCF), bone density and bone metabolism. Method: One hundred and sixteen patients with OVCF operation were randomly divided into control group (58 cases) and observation group (58 cases) by random number table. Patients in control group got Alendronate sodium tablets, 70 mg/time, 1 time/week. Menatetrenone soft capsules, 15 mg/time, 3 times/days after meals. Calcium carbonate D₃ chewable tablets (Ⅱ), 1 tablet/time, 2 times/days. Based on the treatment in control group, patients in observation group received additional Jiawei Bushen Huoxue decoction, 1 dose/day. The course of treatment was 24 weeks in both groups. The treatment of traditional Chinese medicine(TCM) fumigation was used in combination with the TCM for 2 weeks. At the 4^th, 8^th, 12^th and 24^th weeks after treatment, pain degree of waist and back were evaluated by pain visual analogue scale (VAS), and waist dysfunction was evaluated by Oswestry disability index (ODI). Before and after treatment, anterior vertebral height (AVBH), Cobb, femoral neck, lumbar spine bone mineral density and Chinese osteoporosis quality of life scale were evaluated. Before and after treatment, levels of carboxy terminal propeptide of type I collagen (CICP), C-terminal cross-linking peptide of type I collagen (CTX-I), tartrate resistant acid phosphatase (TRACP), bone alkaline phosphatase (BALP) and bone glaprotein(BGP) were detected. Result:By rank sum test, the clinical efficacy in observation was better than that in control group (Z=2.026, P<0.05). At the 4^th, 8^th, 12^th and 24^th weeks after treatment, scores of lumbago and back pain VAS and ODI were lower than those in control group (P<0.01). AVBH, femoral neck bone mineral density, and lumbar spine bone mineral density in observation group were higher than those in control group (P<0.01). Cobb angle was smaller than that in control group; and the four dimension scores of COQOL were lower than those in control group (P<0.01). Levels of BALP, CICP, CTX-I and TRACP in observation group were lower than those in control group (P<0.01), and BGP was higher than that in control group (P<0.01). Conclusion:Jiawei Bushen Huoxuetang can enhance bone mineral density, regulate bone metabolism, reduce back pain, promote healing of fracture, and ameliorate osteoporosis, with obvious clinical efficacy.

Objective:To observe the short-term clinical efficacy of addition and subtraction therapy and external washing treatment of Danggui Niantongtang to knee osteoarthritis (KOA) with heumatism heat Bi syndrome and to investigate its effect on disease activity. Method:One hundred and eighteen patients with KOA were randomly divided into control group (58 cases) and observation group (60 cases) by random number table. Patients in control group got celecoxib capsules, 0.2 g/time, 1 time/day, diclofenac diethylamine emulgel for the pain, 3 times/days. Patients in observation group got addition and subtraction therapy and external washing treatment of Danggui Niantongtang. The course of treatment was 2 weeks in both groups. Before treatment and at the 2^th, 4^th, 6^th and 14^th weeks after treatment, scores of visual analog scale (VAS) were graded for pain in walking and tranquillization. Function of knee joint was evaluated by western Ontario and McMaster university osteoarthritis index (WOMAC) both before and after treatment. Scores of heumatism heat Bi syndrome and Japanese Orthopaedic Associate (JOA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), superoxide dismutase (SOD), interleukin-1β (IL-1β), interleukin-6, tumor necrosis factor-α (TNF-α) and matrix metalloproteinases-3 (MMP-3) levels were evaluated. Result:At the 6^th and 14^th weeks after treatment, scores of VAS in observation group were lower than those in control group during walking and tranquillization time. Scores of three dimensions in WOMAC (pain, stiffness, joint function) and the total score of WOMAC in observation group were all lower than those in control group (P<0.01). The score of main symptoms of heumatism heat Bi syndrome and the total score in observation group were lower than those in control group (P<0.01). After treatment, levels of ESR, CRP, IL-1β, IL-6, TNF-α and MMP-3 were lower than those in control group, and level of SOD was higher than that in control group (P<0.01). Conclusion:Addition and subtraction therapy and external washing treatment of Danggui Niantongtang can relieve the pain and degree of disease caused by KOA with heumatism heat Bi syndrome, swelling and dysfunction, and can control acute inflammation index, reduce disease activity.

Objective To establish a predictive model for inpatients of cardio-cerebrovascular disease in rural areas of Wugang through time series analysis, and predict the changing trend of cardio-cerebrovascular disease, so as to offer guidance for the health care resources allocation and prevention and control of cardio-cerebrovascular disease. Methods The seasonal autoregressive integrated moving average model (SARIMA) was constructed based on the monthly number of cases of cardio-cerebrovascular disease in rural areas from January 2013 to December 2016 by Stata 14.0 software, and the predictive effect of the model was verified with the monthly number of inpatients of cardio-cerebrovascular disease in 2017. Results The final fitting model of inpatients of cardio-cerebrovascular disease was SARIMA (2, 1, 1)×(0, 1, 0)12. The residual sequence of the model was diagnosed. Results of Ljung-Box Q test showed that the residual sequence was white noise sequence (Q=11.12, P=0.68). In addition, the 2017 forecast was basically consistent with the observations, the overall relative error was around -1.2%. The results showed that the summer was the peak period of cardiovascular and cerebrovascular hospitalization. Conclusion SARIMA model can accurately predict the number of inpatients of cardio-cerebrovascular disease in Wugang, which can provide data support for the hospital administrator to rationally allocate medical resources in the cardiovascular according to the needs of cardio-cerebrovascular treatment in different months.

Objective To investigate the clinical features of patients with acute ST-segment elevation myocardial infarction (STEMI) comorbid with diabetes mellitus (DM) and to analyze the prognosis within 12 months after primary percutaneous coronary intervention (pre-PCI). Methods A total of 375 STEMI patients were divided into the diabetes group (n=140) and the normal blood glucose group(n=235) according to whether they met the diagnostic criteria of DH. The clinical data,characteristics of coronary artery lesions,type of stent implant,rate of coronary slow flow or no-reflow after pre-PCI, and the prognosis within 12 months after PCI of the two groups were investigated.Results Patient in the diabetes group presented with higher mean age ,higher comorbid rates of hypertension , hyperlipidemia and heart function of Killip class Ш and above than patients in the normal blood glucose group (all P<0.05). patients in the diabetes group had higher rates of slow reflow /no-reflow after PCI(12.9% vs.5.5%,P=0.013),higher percentages of 3-ressel disease(40.7% vs. 28.9%,P=0.019)and lef t main lesions(13.6% vs. 7.2%,P=0.044). The in-hospital mortality rates(6.4% vs.1.7%,P=0.020),revascularization rates within 12 months(7.9% vs.0.9%,P=0.001)and incidence of heart failure(7.9% vs. 2.6%,P=0.017)were all higher in the diabetes group. Conclusions STEMI patients comorbid with DM were relatively older, had higher comorbidities of hypertension,hyperlipidemia, three-vessel disease, left main coronary lesions and higher mortality during hospitalization. No significant increase in cardiac death and recurrent myocardial infarction were deserved during the follow-up period. These patients may benefit more from early intervention.