The functional realization of proteins and other biological macromolecules depends on conformational dynamics and allosteric regulation, and elucidating their molecular mechanisms is an important foundation for understanding life processes. Molecular dynamics simulations are a powerful tool for investigating conformational evolution at the atomic level. However, traditional methods are limited by simulation timescales and high free-energy barriers, making it difficult to effectively capture rare conformations and their transition pathways. As a result, the development of enhanced sampling techniques has become key to overcoming this bottleneck. As a classical enhanced sampling technique, metadynamics suffers from several shortcomings, including strong dependence on collective variables and significant errors caused by bias potential accumulation. This article reviews three major improvement strategies. The first combines stochastic resetting with metadynamics, using trajectory-resetting mechanisms to improve sampling efficiency while avoiding the difficulty of optimizing collective variables. The second, SinkMeta, employs a “sinking” bias effect to enable efficient exploration of specific regions and paths. The third, OPES-based hybrid methods, improve the stability of free-energy estimation by optimizing the target distribution or the way the bias is constructed. These methods provide new ideas for characterizing free-energy landscapes and studying conformational transitions in complex biological systems, while also promoting the continued development of enhanced sampling methodologies.

BACKGROUND: Reports on the prevalence of psoriatic arthritis (PsA) among Chinese patients with psoriasis are very limited. This study, conducted by rheumatologists, estimated the prevalence of PsA in a large number of Chinese patients with psoriasis. METHODS: Consecutive patients with a confirmed diagnosis of psoriasis attending nine dermatology clinics in five hospitals were recruited. All psoriasis patients were asked to complete a questionnaire comprising 16 questions to identify possible cases of PsA. All patients with one or more positive answers to the questionnaire were evaluated by two experienced rheumatologists. RESULTS: A total of 2434 psoriasis patients, including 1561 males and 873 females, were enrolled. Both the questionnaire and rheumatologists' examinations were completed in the dermatology clinics. The results identified 252 patients with PsA, comprising 168 males and 84 females. The overall prevalence of PsA among psoriasis patients was 10.4% (95% confidence interval [95% CI], 9.1%-11.7%). By sex, the prevalence was 10.8% (95% CI, 9.2%-12.5%) for males and 9.6% (95% CI, 7.7%-11.9%) for females and there was no significant sex difference in the prevalence of PsA (P = 0.38). Of the 252 PsA patients, 125 (49.6%, 95% CI, 41.3%-59.1%) were newly diagnosed by rheumatologists. Consequently, the prevalence of undiagnosed PsA among psoriasis patients was 5.2% (95% CI, 4.4%-6.2%). CONCLUSION The prevalence of PsA in the Chinese population with psoriasis is about 10.4%, which is almost double that of previous reports in the Chinese population, but lower than that in Caucasians.
Humans ; Female ; Male ; Arthritis, Psoriatic/epidemiology* ; Rheumatologists ; Prevalence ; East Asian People ; Psoriasis/epidemiology*

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

Objective:To analyze the changes of bone mineral density (BMD), the characteristics of bone metabolic markers and related factors in patients with spinal cord injury (SCI). Methods:A total of 78 patients with SCI in our hospital from April, 2018 to May, 2020 were selected and divided into groups according to the injury courses. The people receiving physical examination in the same period were selected as control. BMD of proximal femur was measured by dual energy X-ray absorptiometry. Bone metabolic markers were detected. The correlation between BMD and clinical indicators was analyzed. Results:There was no difference in BMD between the patients within three months and the controls (P > 0.05). BMD at trochanter major, intertrochanteric and total hip in patients three to six months post injury was lower than that in the controls (|t| > 2.242, P < 0.05). The BMD at femoral neck, trochanter major, intertrochanteric and total hip in patients during six to twelve months post injury was lower than that in the controls (|t| > 2.026, P < 0.05). BMD at proximal femur in patients with twelve to 24 months post injury was lower than that in the controls (|t| > 2.189, P < 0.05). The decrease of BMD aggravated with the course of injury. There was no difference in BMD between paraplegia and quadriplegia, complete injury and incomplete injury (P > 0.05). Collagen type I C-terminal telopeptide (CTX) and N-terminal propeptide of type l precollagen (PINP) were higher than the reference range in the course of each injury, increased within three months post injury, reached the peak at three to six months post injury, and decreased to a steady state since seven months post injury. Vitamin D deficiency occurred in 87.5% of the patients. BMD at femoral neck and total hip was negatively correlated with the course of injury (|r| > 0.250, P < 0.05), and positively correlated with body mass index (r > 0.255, P < 0.05). Conclusion:The longer the duration of SCI, the more decrease of BMD. The early bone metabolism of patients with SCI is high conversion type. The rate of vitamin D deficiency in patients with SCI is quite high. It is necessary to detect and evaluate the bone metabolic markers combined with BMD at the early stage of SCI.

ObjectiveTo analyze the timeliness of health science popularization during the outbreak of coronavirus disease 2019 （COVID-19） and its correlation with the epidemic situation and policies. MethodsThe original reports of health science popularization by 26 major media in Shanghai during the COVID19 outbreak between January 19 and March 25 of 2020 were retrieved， and the timeliness of the number of reports， media sources and categories， and contents were analyzed. ResultsDuring the epidemic of COVID-19， public media reported timely. Online media accounted for 63.35%， and text-based reports accounted for 85.90%. There was a correlation between the trend of the number of reports and the development of COVID-19 and the prevention and control policy issued by the government. After the change in the epidemic or the release of policy， the number of reports increased. The top four topics were personal protection， disease treatment， healthy lifestyle and psychological health， accounting for 18.62%， 18.54%， 12.96% and 11.74%， respectively. Reports focused on different aspects at different stages of COVID-19 epidemic， and the number of reports tended to increase one week after the occurrence of major events. ConclusionDuring the COVID-19 epidemic， the coverage of health science on media is timely and targeted. For future similar public health emergencies， it is suggested to respond quickly to major events according to the trend， to carry out publicity timely， to innovate the report forms， and thus make it easy for the public to accept and implement.

Sharp injury is a common occupational injury occurs in hospital, it is also an important way for health care workers to be infected with blood-borne pathogens, standardized use of sharps containers can effectively prevent the occurrence of sharp injury.Sharps containers are widely used in China, but the specifications are limited and the products are single, there is still room for improving safety performance.In view of the problems existing in clinical use, Chinese scholars have made a lot of improvements on sharps containers.The author suggests that relevant units should consider the design concept of clinic to develop and popularize more reasonable safe sharps containers for clinical application, and take other comprehensive behavioral control measures, so as to effectively reduce the occurrence of sharp injury.

Clinical breakpoints are used in phaseⅡorⅢclinical trials to categorize microorganisms if susceptibility to new tested antibacterial agents that means the patient infected by the pathogen will be enrolled the study or not.The role of this consensus is to define procedure and required data to setting breakpoints and how to revaluate it in clinical trials.

BACKGROUNDThe induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction.

METHODSIslet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.

RESULTSIslets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 ± 1.19) and (16.88 ± 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher.

CONCLUSIONSThe HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.

Animals ; Blotting, Western ; Graft Survival ; Heme Oxygenase-1 ; genetics ; metabolism ; Interleukin-10 ; blood ; Islets of Langerhans ; enzymology ; metabolism ; Islets of Langerhans Transplantation ; Male ; Mice ; Mice, Inbred BALB C ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous

OBJECTIVESTo investigate the prevalence of celiac disease in children with chronic diarrhea in China.

METHODSInpatients of the pediatric hospitals in Shanghai, Jinan, Wuhan and Chengdu who were diagnosed as chronic diarrhea were recruited from Jan. 2005 to Dec. 2008. Their clinical history, physical examination and laboratory data were collected. The SPSS version 11.5 statistical package for Microsoft Windows was used for statistical analysis.

RESULTSData of 199 patients and finally enrolled 118 hospitalized chronic diarrhea inpatients during the observation period were collected and 14 (12%) of the chronic diarrhea patients were suspected as having celiac disease and in one the diagnosis of celiac disease was confirmed. Gluten-free diet (GFD) treatment was effective. M/F: 12/2, the age ranged from 6 months to 12 years; 43% (6/14) had malnutrition, 29% (4/14) had anemia, villous atrophy was found in 4 patients by endoscopy. Duodenal biopsies revealed stage I in 1, stage II in 2, stage IIIa in 7, stage IIIb in 3 and stage IIIc in 1 patient according to the modified Marsh classification.

CONCLUSIONThis study was the first time to report the research of celiac disease in children with chronic diarrhea in China. The percentage of suspicious celiac disease patients was 12% (14/118) in children and one was confirmed. CD exists in China. Chinese pediatricians should pay attention to the disease.

Adolescent ; Celiac Disease ; epidemiology ; pathology ; Child ; China ; epidemiology ; Diarrhea ; epidemiology ; pathology ; Duodenum ; pathology ; Endoscopy, Digestive System ; Female ; Humans ; Infant ; Intestinal Mucosa ; pathology ; Male ; Prevalence

OBJECTIVEVasoactive intestinal peptide (VIP) is a neuro-peptide that can modulate immunity. Previous studies indicated that VIP can attenuate the deleterious consequences of severe sepsis and septic shock by regulating production of inflammatory cytokines in immune activated cells. The signaling induced by bacterial components occurs primarily through Toll like receptors (TLRs). TLRs have been recognized to play a key role in pathogen recognition and innate immunity. It was convincingly demonstrated that lung is one of early suffered disaster organ and may trigger multiple organ dysfunction syndrome in sepsis. The present study was conducted to investigate the effects of VIP on TLR2/4 mRNA expressions on acute lung injury of endotoxic shock induced by lipopolysaccharide (LPS) in rat.

METHODForty Sprague-Dawley rats were randomly divided into 3 groups, i.e., LPS shock group (n = 16), LPS + VIP group (n = 16), and control group (n = 8). LPS shock model was established by LPS (E. coli O(55)B(5) 10 mg/kg) with tail intravenous injection. The rats in LPS + VIP group were given a bolus of 5 nmol VIP intravenous injection follow by LPS. The rats in control group were given normal saline. The rats were sacrificed at 6 h, 24 h after being injected. The lung tissues were collected. The TLR2 mRNA and TLR4 mRNA expressions were detected by RT-PCR from the lung tissues. Pathological changes of the lungs were observed by light microscope and electron microscope 24 h after LPS injection.

RESULT(1) Lung histopathology: the alveolar space was full with leukocyte, necrotic cells, segmental hemorrhage and protein effusion. Partial alveolar space was enlarged, lung interstitial edema were observed in LPS shock group. However, pathological changes of LPS + VIP group were milder than those in LPS shock group. (2) The expressions of TLR2 mRNA and TLR4 mRNA were significantly higher in LPS shock group compared with those of the control group (F = 16.638, P = 0.000; t = 5.876, P = 0.000), TLR2 mRNA and TLR4 mRNA expression on 24 h was down-regulated in LPS + VIP shock subgroup than those in LPS shock subgroup (F = 16.676, P = 0.000; t = 3.946, P < 0.001).

CONCLUSIONExpressions of TLR2 mRNA and TLR4 mRNA were up-regulated on LPS induced lung injury in rats. VIP mitigated lung injury induced by LPS, which may be related to TLR2 mRNA and TLR4 mRNA down-regulation of expression. The effect of VIP may suggest a protective mechanism in sepsis. VIP may play a potential protective role in severe infection.

Acute Lung Injury ; chemically induced ; metabolism ; pathology ; Animals ; Down-Regulation ; Lipopolysaccharides ; Lung ; metabolism ; pathology ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 2 ; genetics ; metabolism ; Toll-Like Receptor 4 ; genetics ; metabolism ; Up-Regulation ; Vasoactive Intestinal Peptide ; pharmacology