Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.
Animals ; Mice ; Candida albicans ; Candidiasis, Oral/drug therapy* ; Antifungal Agents/pharmacology* ; Hyphae ; Artemisinins/pharmacology*

Objective:The epidemiological and clinical characteristics of 18 cases of Japanese spotted fever (JSF) in Zigui County were analyzed in order to improve the prevention and treatment of JSF.Methods:This is a case series analysis. The epidemiological and clinical data, laboratory tests and imaging characteristics of 18 JSF cases with median age of 60 years (54, 68) identified by The People′s Hospital of Zigui from April 2021 to August 2022 were collected and analyzed retrospectively.Results:Most (17/18) of the patients were farmers and all had a field exposure history. The patient′s onset was from April to October. Spring and autumn were the seasons with the highest incidence of JSF. The first symptoms of patients were high fever, headache, and fatigue. Of the 18 cases, 15 had a rash and 12 presented an eschar and 3 had neither rash nor eschar. In addition, 10 of 18 cases experienced edema of both lower extremities, and 3 got disturbance of consciousness. Laboratory tests found that 15 patients had abnormal white blood cells and 11 patients had decreased platelets. C-reactive protein, procalcitonin, D-dimer, lactate dehydrogenase, and alpha-hydroxybutyrate dehydrogenase were elevated in all patients; 13 patients with elevated alanine aminotransferase, 14 patients with elevated aspartate transamination. Kidney damage caused by Rickettsia japonica infection showed by abnormal proteinuria in 11 of the patients. Conclusions:The most common clinical manifestations of JSF are non-specific indications such as high fever, chills, fatigue, headache. The eschar and rash, which are the main features of Rickettsia infection, are not present in all patients, resulting delay of diagnosis or misdiagnosis. Medical workers should be more alert to rickettsial infections in patients with fever of unknown origin, especially in seasons of high incidence of spotted fever. Early diagnosis and correct antibiotic treatment shall be given according to the patient′s clinical manifestations, laboratory results and imaging test to control disease progression.

Objective:To evaluate the effect of electroacupuncture on the heme oxygenase-1 (HO-1)/PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway during acute kidney injury in endotoxemic rats.Methods:Twenty-four SPF healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 180-220 g, were divided into 4 groups ( n=6 each) by a random number table method: control group(group C), endotoxemia group(group E), acupoint electroacupuncture+ endotoxemia group(group EE), and non-acupoint electroacupuncture+ endotoxemia group(group NE). The endotoxemia model was developed by intraperitoneal injection of lipopolysaccharide 10 mg/kg. The equal volume of normal salinewas injected in group C. LPS 10 mg/kg was intraperitoneally injected in group E. In group EE, 30-min electroacupuncture was performed at bilateral Zusanli and Shenshu acupoints using disperse-dense waves with a frequency of 2/15 Hz to induce slight muscle tremor once a day starting from 5 days before developing the model, and the needle was retained until 6 h after injection. Electroacupuncture was performed at the points 0.5 cm lateral to the acupoints of Zusanli and Shenshu in group NE. The rats were anesthetized at 6 h after lipopolysaccharide injection, and blood samples from the femoral vein were obtained for determination of the serum creatinine (Cr) and urea nitrogen (BUN) concentrations(with a biochemical analyzer) and concentrations of neutrophil gelatinase-associated lipid transport protein (NGAL), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and kidney injury molecule-1(KIM-1) in serum (by enzyme-linked immunosorbent assay). Then the rats were sacrificed and kidney tissues were taken for determination of histological score of kidneys (HSK, using HE staining) and expression of HO-1, PINK1, Parkin, mitochondrial fusion protein 2(Mfn2), optic atrophy protein 1(OPA1) and mitochondrial dynamic-related protein 1 (Drp1) (by Western blot). Results:Compared with group C, serum concentrations of Cr, BUN, KIM-1, NGAL, IL-6 and TNF-α and HSK score of renal tissues were significantly increased, the expression of HO-1, PINK1, Parkin and Drp1 was up-regulated, and the expression of Mfn2 and OPA1 was down-regulated in E, EE and NE groups ( P<0.05). Compared with group E, serum concentrations of Cr, BUN, KIM-1, NGAL, IL-6 and TNF-α and HSK score of renal tissues were significantly decreased, and the expression of HO-1, PINK1, Parkin, Mfn2 and OPA1 was up-regulated, and Drp1 expression was down-regulated in group EE( P<0.05), and no significant change was found in the parameters mentioned above in group NE ( P>0.05). Conclusions:The mechanism by which electroacupuncture alleviates acute kidney injury is associated with activation of HO-1/PINK1/Parkin signaling pathway in endotoxemic rats.

Objective:To evaluate the effect of ozone preconditioning on splenic natural killer (NK) cells in septic mice.Methods:Twenty-four SPF-grade male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) according to the random number table method: control group (group C), lipopolysaccharide (LPS)group, ozone+ LPS group (O 3+ LPS) and air+ LPS group (Air+ LPS). The sepsis was induced by intraperitoneal injection of LPS 10 mg/kg. Ozone preconditioning was started at 5 days before developing the model: ozone 1 mg/kg was intraperitoneally injected once a day for 5 consecutive days, the equal volume of air was injected in Air+ LPS group. The survival was observed within 72 h after LPS injection, and sepsis score and ear temperature (once every 2 h, an average was calculated) were recorded. The posterior orbital venous blood samples were taken at 6 and 24 h after LPS injection for determination of serum interferon-γ (IFN-γ) and interleukin-10 (IL-10) concentrations using enzyme-linked immunosorbent assay. The spleen was then taken, and a single cell suspension of the spleen was prepared for measurement of the percentage of NK cells in the spleen by flow cytometry. Results:Compared with C group, the ear temperature, sepsis score and 72-h survival rate were significantly decreased, serum IFN-γ and IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was increased at 6 h after LPS injection and decreased at 24 h after LPS injection in LPS, Air+ LPS and O 3+ LPS groups ( P<0.05). Compared with LPS group, the ear temperature, sepsis score and 72-h survival rate were significantly increased, serum IFN-γ concentrations were decreased at each time point after LPS injection, serum IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was decreased at 6 h after LPS injection and increased at 24 h after LPS injection in O 3+ LPS group ( P<0.05), and no significant change was found in the parameters mentioned above in Air+ LPS group ( P>0.05). Conclusions:The mechanism by which ozone preconditioning reduces sepsis may be related to reduction of inflammatory responses and regulation of splenic NK cell levels in septic mice.

Objective:To investigate the safety and efficacy of remimazolam combined with afentanyl for fiberoptic bronchoscopy.Methods:Sixty patients admitted to Chifeng Hospital for fiberbronchoscopy from January to April 2022 were selected and divided into two groups by random number table method: remimazolam group (group R) and propofol group (group P), 30cases in each group. After intravenous injection of alfentanil for anesthesia induction, group R was sedated by intravenous injection of remidazolam besylate, and group P was sedated by intravenous injection of propofol emulsion. When sufficient sedation was achieved, fiberoptic bronchoscopy was performed. The patients were scored with the Mini-Mental State Examination (MMSE) before examination and before leaving the room. The recovery rate of sedation and the recovery rate of drugs during operation were compared. Blood pressure, heart rate (HR), bispectral index (BIS), SpO 2 value and Modified Observer′s Assessment of Alertness/Sedation (MOAA/S) score were compared before induction (T 0), at the beginning of examination (T 1), immediately when fiber bronchoscope reached juga (T 2), at the end of surgery (T 3), immediately, when patients regained consciousness (T 4). Drug onset and recovery time (time out of hospital) as well as the incidence of intraoperative and postoperative adverse reactions were recorded in both groups. Results:There was no statistically significant difference in general condition, MMSE score and examination time between the two groups (all P>0.05). There was no statistically significant difference between the two groups in the success rate of sedation and the number of sedative remedy times (all P>0.05). The number of additional drugs in group R was significantly higher than that in group P ( P<0.05). The systolic blood pressure, diastolic blood pressure and BIS values of patients in group P at T 1 and T 2 were significantly lower than those in group R (all P<0.05). After administration, the MOAA/S score of the two groups began to decrease, and the decrease of the P group was significantly greater than that of the R group, and the MOAA/S value of the patients was the lowest at the 3rd and 4th minutes after administration, respectively. The time from the beginning of administration to the MOAA/S score ≤3 in group P was significantly shorter than that in group R (all P<0.05). The incidence of pain and respiratory depression after injection in group P was significantly higher than that in group R ( P<0.05). Conclusions:The application of afentanil combined with remimazolam in the patients undergoing fiberoptic bronchoscopy has good sedative effect and high anesthesia quality, and has no obvious effect on cognitive function and few adverse reactions, so it is safe and effective.

Objective:To systematically evaluate the effect of melatonin on postoperative sleep quality.Methods:Databases such as PubMed, Embase, Cochrane library, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure, Wanfang Database, China Biomedical Literature Database and China Science and Technology Journal Database were searched from inception to January 30, 2022 for randomized controlled trials (RCTs) comparing the effects of melatonin versus placebo on postoperative sleep quality.The outcomes analyzed were visual analog scale (VAS) score, sleep quality scale score, subjective sleep scale score, St.Mary′s Hospital sleep questionnaires score, sleep latency, total sleep time, number and duration of awakenings, and incidence of postoperative sleep disturbance.Statistical analysis was performed using the RevMan 5.4 software and Stata 16 software, and the trial sequential analysis (TSA) was conducted using the TSA 0.9.5.10 Beta software. Results:Eleven RCTs involving 822 patients were finally enrolled, with 431 patients in melatonin group and 391 patients in placebo group.The results of meta-analysis showed that melatonin significantly decreased postoperative VAS and sleep quality scale scores, and increased the postoperative subjective sleep scale and St.Mary′s Hospital sleep questionnaires scores, a daily dose of melatonin 6 mg produced a better efficacy, and it also prolonged the postoperative total sleep time and decreased the incidence of postoperative sleep disorders ( P<0.05), However, it had no effect on postoperative sleep latency and the number and duration of awakenings ( P>0.05). The results of TSA showed that although the actual sample size did not reach the expected sample size, the accumulated Z value crossed the traditional boundary value and the TSA boundary value, which indicated that the results of this meta-analysis had stability and further confirmed the efficacy of melatonin in improving postoperative sleep quality. Conclusions:Melatonin can improve postoperative sleep quality and a daily dose of melatonin 6 mg exerts a better efficacy.

Objective:To evaluate the sedative efficacy of remimazolam in outpatients undergoing curettage.Methods:Eighty outpatients, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, aged ≥18 yr, undergoing curettage, were divided into 2 groups according to the random number table method: remimazolam group (group R, n=41) and propofol group (group P, n=39). Anesthesia was induced with alfentanil 10 μg/kg injected intravenously in two groups, and in addition remimazolam 7 mg was intravenously injected in group R, and propofol 1.5 mg/kg was intravenously injected in group P. If the Modified Observer′s Assessment of Alertness/Sedation score ≥3 or the patient could not tolerate the surgical procedure, remimazolam 2.5 mg was given for rescue sedation in group R and propofol 0.5 mg/kg was given for rescue sedation in group P, and alfentanil 1 μg/kg was given as rescue analgesic.The onset time of sedatives, time to eye opening, emergence time and time to discharge were recorded.The success of sedation, intraoperative BIS value, requirement for rescue medications, and occurrence of adverse reactions were recorded. Results:The intraoperative BIS values were maintained at 61-72 and 40-64 in group R and group P, respectively.The success rate of sedation was 95% in group R and 100% in group P, and there was no significant difference between the two groups ( P>0.05). Compared with group P, the rate of rescue sedative agents used and rate of rescue alfentanil given were significantly increased, the onset time of sedative agents was significantly prolonged, the incidence of postoperative nausea and vomiting was increased, and the incidence of respiratory depression and injection pain was decreased in group R ( P<0.05 ). Conclusion:Remimazolam (given according to the instructions) is safer when used for outpatient curettage, but it can only maintain a light sedation status, and the sedative efficacy is inferior to propofol.

Malignant tumors in the head and neck seriously threaten the physical and mental health of patients. After treatment, they may cause many complications, such as facial deformity, difficulties with chewing, dysphagia and asaphia. Among them, trismus (restricted mouth opening) is one of the most common complications after treatment of malignant oral-maxillofacial tumors. In severe cases, patients may even suffer from trismus and eating difficulties, finally leading to malnutrition and even cachexia. Therefore, it not only affects the quality of life of patients and even endangers their lives but also brings heavy social and economic burdens. How to effectively prevent and treat posttreatment trismus is a clinical problem that is easily ignored by head and neck surgeons and urgently needs to be solved. The results of a literature review showed that trismus may be related to the tumor clinical stage, tumor site, treatment used, radiotherapy site, radiotherapy dose, radiotherapy type, and other factors. The incidence of trismus tends to be significant 6 months after treatment. Without early intervention, the resulting dysfunction may become more severe. Current studies have shown that the prevention and treatment of restricted mouth opening is based on controlling the progress of restricted mouth opening and restoring function. Exercise intervention for trismus can significantly improve the restricted mouth opening of patients with malignant head and neck tumors after treatment.

Objective:To evaluate the relationship between red blood cell distribution width (RDW) and metabolic syndrome (MS) in patients with impaired glucose tolerance (IGT).Methods:A total of 415 patients with abnormal glucose tolerance were screened by oral glucose tolerance test in Changsha Traditional Chinese Medicine Hospital (Changsha Eighth Hospital) from October 2015 to September 2019. General data were collected and blood routine and biochemical indexes were detected. There were 193 cases in the observation group and 222 cases in the control group. The RDW and other clinical indicators were compared between the two groups, the correlation between RDW and other indicators was analyzed, and the risk factors of metabolic syndrome were analyzed.Results:⑴ The RDW, systolic blood pressure (SBP), diastolic blood pressure (DBP), height (Ht), weight (Wt), waist circumferenc (Wc), triglyceride (TG), cholesterol (CHOL), low density lipoprotein (LDL), creatinine (Cr), uric acid (UA), alanine aminotransferase (ALT), high sensitive C-reactive protein (hs-CRP), body mass index (BMI) of the observation group were significantly higher than those of the control group, while the high density lipoprotein (HDL) was significantly lower than that of the control group, with statistically significant difference ( P<0.05); ⑵ correlation analysis showed that RDW was positively correlated with SBP, DBP, Ht, Wt, Wc, TG, CHOL, Cr, UA, ALT, hs-CRP, BMI, and negatively correlated with HDL ( P<0.05); ⑶ binary logistic regression analysis showed that RDW, Wt, Wc, CHOL, HDL, LDL and hs-CRP were independent risk factors for MS in patients with impaired glucose tolerance. Conclusions:The increase of RDW is a predictor of metabolic syndrome in people with abnormal glucose tolerance, which may provide some reference value for the prevention and treatment of metabolic syndrome.

Allografts ; COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Kidney Transplantation/adverse effects* ; SARS-CoV-2