Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective:To observe the effect of large pushing Tianheshui manipulation intervention on the body temperature of young rabbits with endotoxin-induced fever and discuss its antipyretic mechanism.Methods:Thirty-two young rabbits meeting the standards were selected from 40 ordinary young male New Zealand rabbits after being adapted for 7 d,and randomly divided into a normal group,a model group,a large pushing Tianheshui group,and an ibuprofen group according to the random number table method,with 8 rabbits in each group.Rabbits in the model group,the large pushing Tianheshui group,and the ibuprofen group were subjected to preparing the endotoxin-induced fever model by intravenous lipopolysaccharide from the marginal ear vein.Rabbits in the large pushing Tianheshui group received Tuina(Chinese therapeutic massage)manipulation intervention 1.5 h and 2.5 h after modeling,respectively.Rabbits in the ibuprofen group were intragastrically given ibuprofen suspension 1.5 h after modeling.The dynamic changes in body temperature were observed for the young rabbits after fever modeling.Enzyme-linked immunosorbent assay was used to determine the content changes in positive mediators of hypothalamic body temperature,including prostaglandin(PG)E2 and cyclic adenosine monophosphate(cAMP),as well as negative mediators of hypothalamic body temperature,including arginine vasopressin(AVP)and α-melanocyte stimulating hormone(α-MSH).Results:The body temperature of the young rabbits in the model group was significantly higher than that in the normal group at 0.5-4.0 h,5.0 h,and 5.5 h after modeling(P＜0.01),showing two obvious fever peaks in the model group at 1.5 h and 3.0 h after modeling,respectively,with the highest peak at 1.5 h.Compared with the model group,body temperatures of the large pushing Tianheshui group and the ibuprofen group decreased significantly after 0.5 h of intervention(P＜0.05).Compared with the normal group,the contents of PGE2 and cAMP were significantly increased(P＜0.05),and the contents of AVP and α-MSH were significantly decreased(P＜0.01)in the hypothalamus of the model group.Compared with the model group,the contents of PGE2 and cAMP were significantly decreased(P＜0.01),and the levels of AVP and α-MSH were significantly increased(P＜0.01)in the hypothalamus in the large pushing Tianheshui group and the ibuprofen group.There were no significant differences in the PGE2,cAMP,AVP,and α-MSH contents in the hypothalamus between the ibuprofen group and the large pushing Tianheshui group(P＞0.05).Conclusion:Large pushing Tianheshui manipulation has a significant antipyretic effect on endotoxin-induced fever in young rabbits.The mechanism may be related to inhibiting the positive regulators(PGE2 and cAMP)and promoting the negative regulators(AVP and α-MSH)of hypothalamic control of body temperature.

Objective:To explore the definition and implications of occupational attractiveness among long-term caregivers.Methods:The Walker and Avant concept analysis method was used to define the concept of occupational attractiveness among long-term caregivers.Results:Attributes of occupational attractiveness of long-term caregivers were: (ⅰ) a strength or ability; (ⅱ) mutual attraction between long-term care occupations and incumbents and potential job seekers; (ⅲ) to attract potential job seekers and satisfying their willingness to work; (ⅳ) to retain and motivate in-service long-term care personnel, and enabling them to develop the professional identity and career development.Conclusions:This concept is defined from the perspective of nursing practice in the elderly care service industry in China and combined with the characteristics of long-term caregivers at this stage. It provides clear conceptual support for further relevant research, and provides certain theoretical and practical guidance for the long-term care work of elderly care institutions, communities and families in China.

Chitosan is a natural polysaccharide that is widely used in food, textile, cosmetics, and medical industries. In the field of stomatology, chitosan and its derivatives are widely used in the treatment of many common oral diseases due to a variety of excellent biological properties, such as anti-infection, drug-loading, remineralization and osteogenesis. This review summarized the latest advances in the biological properties of chitosan and its derivatives, as well as their applications in the prevention and treatment of oral diseases.
Anti-Infective Agents ; Chitosan

Objective:To evaluate the effectiveness of Orem self-care model for elderly patients with hip fracture.Methods:The databases including Medline, Embase, Web of Science, Cochrane Library Database, Wanfang, CNKI, VIP, and CMB were searched from inception to September 2020. All randomized controlled trials (RCTs) of the Orem self-care model applied in elderly patients with hip fracture were included. Two investigators independently screened research, extracted data and assessed the quality of literature based on standard methods. RevMan 5.3 software was performed to conduct the Meta-analysis.Results:A total of 11 RCTs were included, involving 1 088 patients. Compared with conventional nursing model, self-care model could effectively reduce the incidence of complications during hospitalization ( RR=0.26, 95% CI 0.18-0.39, P<0.001) and improve the Harris scores ( MD=13.33, 95% CI 11.09-15.57, P<0.001) of elderly patients with hip fracture. However, the impacts of self-care model on alleviating postoperative pain was still uncertain. Additionally, the self-care model could shorten hospital stay, but the combined effect size was unavailable due to the high heterogeneity between related studies. Conclusions:In comparison with conventional nursing model, the Orem self-care model was more beneficial to shorten the hospitalization stay, reduce the incidence of postoperative complications and promote hip joint function of elderly patients with hip fractures. To confirm the effectiveness of self-care models in pain management for elderly patients with hip fractures, multicenter RCTs with high quality and large samples are needed.

Candida albicans (Ca) is an important opportunistic pathogenic fungus found in the oral cavity, which plays an important role in oral microecological balance, and often interacting with other bacteria including Streptococcusmutans (Sm). Meanwhile, the characteristics of Ca such as adhesion, acidogenicity, aciduric nature and the ability to produce collagenolytic proteinases indicate its latent cariogenic potential. This review summarizes the research progress of the detectable rate of Ca in caries, its cariogenic potential and the interaction with Sm and other oral bacteria, in order to extend the understanding of pathogenesis of dental caries and to contribute new therapeutic and preventive strategies for dental caries.

OBJECTIVE: To explore the genetic basis for a sporadic case with neurofibromatosis type 1 (NF1). METHODS: Peripheral blood samples were collected from the patient, his unaffected parents and 100 healthy controls. The NF1 gene was detected by PCR and direct sequencing. RESULTS: The patient was found to carry a novel nonsense variant c.4339C>T (p.Q1447X) in exon 33 of the NF1 gene. The same variant was not found in his unaffected parents and the 100 healthy controls. CONCLUSION The c.4339C>T (p.Q1447X) variant probably underlies the pathogenesis of NF1 in this patient.

Objective:To evaluate the feasibility of low-voltage, low-concentration, and low-volume iodine contrast agent for coronary artery CT imaging in patients with chronic kidney disease (CKD).Methods:A total of 36 patients from July 2016 to January 2018 with CKD who were suspected of having coronary artery disease (CAD) were selected prospectively and were performed with coronary artery CT angiography (CCTA) by randomly divided into control group and observation group. In the control group, 13 patients were scanned with a conventional tube voltage of 120 kV, a step-and-shot (SAS) scanning protocol, 63-85 ml injection of a high-concentration iodine contrast agent (iopromide, 370 mg I/ml), and traditional filtered back projection (FBP) reconstruction algorithm. In the observation group, 23 patients were scanned with a low-voltage SAS scanning scheme based on body mass index (BMI) (100 kV for BMI ≥ 25 kg/m 2 or 80 kV for BMI<25 kg/m 2), isotonic low-concentration iodine agent(iodixanol, 270 mgI/ml), low volume injection (45 ml) and iterative algorithm reconstruction algorithm. The scans for both groups of patients were turned on automatic tube current modulation (4D CareDose). The coronary artery image quality of the two groups was evaluated with subjective and objective method. The radiation dose was calculated based on the product of the dose length product (DLP) and the chest coefficient k. The total iodine intake of the two groups was calculated by the product of the iodine concentration and the injection volume. Changes in renal function were calculated as a percentage decrease in serum creatinine clearance before and on day 3 after examination. Results:Totally 32 patients were performed CCTA successfully. Subjective scores of coronary artery image quality in the control and observation groups were 3.789±0.598 and 3.708±0.717, respectively, with no significant statistically difference( P>0.05). The signal noise ratios were 12.88±4.53 and 13.67±2.08(LAD), 11.9±5.0 and 12.6±5.1(RCA), 12.78±3.15 and 13.22±3.10(LCX), with no significant statistically difference ( P>0.05). The average contrast noise ratios were 10.94±1.31 and 11.27±1.81 (LAD), 10.38±1.90 and 11.01±2.26 (RCA), 11.71±3.15 and 12.49±3.62 (LCX), with no significant statistically difference ( P> 0.05). The average radiation doses in observation and control group were (1.09±0.19) and (2.85±0.59) mSv, respectively, with statistically significant difference between the two groups ( t=20.260, P<0.05). The average iodine intakes of the control and observation group were (2.71±0.37) and (1.22±0.00) g, respectively, with statistically significant difference ( t=18.162, P<0.05). The decreases of serum creatinine clearance within 72 hours after injection of iodine contrast agent in the control group and observation group were (28.75±5.24)% and (11.89±4.98)%, respectively, with significant statistically difference ( χ2=9.004, P<0.05). Conclusions:Triple-low scanning scheme can reduce the total iodine consumption and radiation dose of patients with little effect on renal function and meeting the diagnostic requirements of image quality. It is suitable for CCTA of patients with CKD.

Objective: To investigate the clinical characteristics, memory and neuroimaging features of nonlesional temporal lobe epilepsy (TLE-NL). Methods: Forty-four patients with TLE-NL and 53 patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) were recruited from the Second Affiliated Hospital of Zhejiang University from September 1st 2012 to August 31st 2017. The clinical characteristics were systematically analyzed and compared between TLE-NL and TLE-HS. Twenty healthy volunteers were also recruited. Memory assessment and high resolution magnetic resonance imaging (MRI) scanning were completed in the patients and healthy volunteers. Volume and shape of the hippocampus were compared between patients and healthy volunteers. Results: Compared with the TLE-HS, TLE-NL patients showed later seizure onset ((24.3±12.6) vs (15.8±10.3) years; t=3.684, P<0.01), shorter duration of epilepsy ((4.00 (2.00, 8.75)) vs (14.00 (7.50, 22.00)) years; Z=-4.675, P<0.01), less history of febrile convulsions (4.5% (2/44) vs 62.3% (33/53); χ²=32.270, P<0.01) and lower incidence of pharmacoresistant epilepsy (47.7% (21/44) vs 84.9% (45/53); χ²=15.282, P<0.01). However, there were no statistically significant differences between TLE-NL and TLE-HS in sex ratio, family history of epilepsy, lateralization of the epileptogenic zone, presence of aura, seizure types and seizure frequency. TLE-NL patients had normal memory quotient compared to normal controls (105.2±17.4 vs 103.8±16.2; P=1.000), while TLE-HS patients had significant memory impairment compared to normal controls (84.5±20.3 vs 103.8±16.2; P<0.01). Compared to normal controls, TLE-NL patients did not have significant alteration in hippocampal volume and shape, while TLE-HS patients had significant atrophy in the ipsilateral hippocampus ((2 953±481) mm³ vs (4 431±505) mm³; P<0.01), and shape analysis showed significant atrophy in the head and body of the hippocampus. Conclusion TLE-NL has different characteristics compared with TLE-HS, including later seizure onset, shorter duration of epilepsy, less history of febrile convulsions, better response to antiepileptic drugs, and no significant memory impairment and hippocampal atrophy.

Enterococcus faecalis is an important pathogen in pulp periapical disease that has been widely studied in recent years. A large number of studies have shown that the high detection rate of Enterococcus faecalis in root canals with persistent or secondary infection after root canal therapy is closely related to the failure of root canal therapy. The presence of Enterococcus faecalis in periapical pulp disease is related to its pathogenicity and virulence factors. Enterococcus faecalis can directly invade host tissues or induce immune inflammation in host tissues, resulting in periapical pulp tissue damage and lesions. Enterococcus faecalis has a strong tolerance to conventional root canal antibiotics and disinfection methods and is difficult to completely remove from the complex root canal system. How to fight Enterococcus faecalis infection has become an important direction in the treatment of pulp periapical disease. This article reviews the pathogenic mechanism of Enterococcus faecalis infection in pulp periapical disease and the progress in its treatment.