Objective·To explore the association between gene-gene interaction of glutamate pathway and anhedonia.Methods·A total of 279 patients with schizophrenia(SZ)and 236 patients with major depression disorder(MDD)recruited in the outpatient department and ward of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 236 healthy controls(HC)recruited in the community from January 2017 to August 2020 were included in the study.General demographic data and clinical characteristics of the three groups were collected and compared.The Chinese version of Temporal Experience of Pleasure Scale(TEPS)was used to evaluate the pleasure experience ability of the three groups.Generalized multifactor dimensionality reduction(GMDR)method was used to establish the interaction model of the single nucleotide polymorphism(SNP)in glutamate pathway genes(NOS1AP,GSK3β,DAOA,DISC1 and GRIN2A).According to the interaction model,SZ and MDD patients were divided into high-risk group and low-risk group,and the differences in pleasure experience ability were compared between the two groups,so as to analyze the effect of gene-gene interaction on anhedonia.Results·There were significant differences in age and years of education among the three groups,and in age of onset and duration of illness between SZ and MDD groups(all P=0.000).There were significant differences among the three groups of participants in terms of overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience(all P=0.000);the overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience in the SZ and MDD group were lower than those in the HC group(all Pcorr=0.000),and there was marginal statistical difference in anticipatory pleasure experience between the SZ and MDD groups(Pcorr=0.051).Through GMDR modeling,it was found that the 2-loci interaction model composed of DAOA-rs3916965 and DISC1-rs821577 had a predictive effect on the overall pleasure experience ability of SZ patients(P=0.003),and the 2-loci interaction model composed of NOS1AP-rs1858232 and GRIN2A-rs1014531 had a predictive effect on the anticipatory pleasure experience ability of MDD patients(P=0.037);moreover,the overall pleasure experience ability of patients in the SZ high-risk group and anticipatory pleasure experience ability of patients in MDD high-risk groups were lower than those in their low-risk groups(t=3.443,P=0.000;t=3.471,P=0.001).Conclusion·The interaction of glutamate pathway gene polymorphisms may be involved in the occurrence of anhedonia.

Topical semi-solid preparations include creams,ointments,gels and other dosage forms,which contain various excipients such as emulsifiers,preservatives,thickeners or emollient agents,etc.They can be single-phase system,or multiple system consisting of continuous phase and disperse phase thanks to its complex design of formulation and manufacturing process.Rheology properties are critical quality attributes of topical semi-solid preparations,which can comprehensively reflect the difference in microstructure such as the substance distribution and aggregation state of the product,and is related to other attributes such as in vitro release,in vitro penetration,stability and cutaneous sense.It is one of the most effective means to evaluate the quality equivalence between generic drugs and innovator drugs.After reviewing domestic,foreign literature and relative policies,this paper described the research status and test methods of rheology,analyzed the possible factors affecting rheological properties,discussed the quality differences reflected in rheological data,in order to guide pharmaceutical manufacturers to improve their formulations and processes and provide help for the development and quality equivalence research of such preparations.

Heterotypic cell-in-cell structures (heCICs) are closely related to tumor development and progression, and have become a new frontier in life science research. Ras-related C3 botulinum toxin substrate 1 (Rac1) belongs to the classic Rho GTPase, which plays a key role in regulating the cytoskeleton and cell movement. To investigate the role and mechanism of Rac1 in the formation of heCICs, tumor cells and immune killer cells were labeled with cell-tracker, respectively, to establish the heCICs model. Upon treatment with the Rac1 inhibitor NSC23766, the formation of heCICs between tumor and immune cells was significantly reduced. The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1. As a result, the formation of heCICs was significantly increased upon Rac1 overexpression. These results demonstrated a promotive role of Rac1 in heCICs formation, which may facilitate treating cell-in-cell related diseases, such as tumors, by targeting Rac1.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To translate the Pressure Ulcer Quality of Life Questionnaire (PU-QOL) into Chinese and test its reliability and validity.Methods:The PU-QOL was translated, back translated, cross-cultural debugged and pre-investigated to form the Chinese version of PU-QOL. From August 2020 to November 2021, 405 patients with PU in wound clinics of two third-class hospitals in north and south regions of China were conveniently selected as the research objects.Results:The Chinese version of PU-QOL had 74 items. The content validity of the items was 0.80 to 1.00 and the content validity of the scale level was 0.95. Exploratory factor analysis extracted 7 common factors and the cumulative variance contribution rate was 60.79%. Each problem area is moderately correlated with the 12-Item Short Form Survey (SF-12), and the correlation coefficient between each dimension (0.13-0.28) was less than the correlation coefficient between each dimension and the total score of the scale and the difference was statistically significant( P<0.01). The Cronbach′s α coefficient was 0.84 and the retest reliability was 0.92. Conclusions:The Chinese version of PU-QOL questionnaire was proved to be a good instrument with acceptable reliability and validity, which can be used as a tool for evaluating quality of life of patients with PU in China.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.

Objective:To investigate the common allergens in children with respiratory allergic diseases in Guangdong and provide the basis for preventing and treating respiratory allergic diseases.Methods:A total of 254 serum samples were collected retrospectively from children with allergic rhinitis and (or) asthma in the pediatric clinic of the First Affiliated Hospital of Guangzhou Medical University or Boai Hospital of Zhongshan City from August 2019 to August 2020 and tested positive for at least one allergens by ImmunoCAP 1000 or skin prick test. There were 173 males and 81 females, with a median age (interquartile interval) of 7 (4.00, 9.75) years. Specific IgE against eighteen common allergen were tested by magnetic particle chemiluminescence immunoassay. Statistical analysis using χ 2 test. Results:The positive rate of Dermatophagoides pteronyssinus (85.0%, 215/254) was the highest, followed by D. farinae (83.5%, 212/254), egg white (19.3%, 49/254), milk (14.6%, 37/254), German cockroach (14.2%, 36/254) and ox-eye daisy (12.6%, 32/254). Dust mites were the most common allergens in patients with allergic rhinitis / allergic asthma / allergic rhinitis and asthma. The positive rates of D. pteronyssinus (95.4% vs. 91.7% vs. 71.0%, χ 2=23.257, P<0.001), D. farinae (95.4% vs. 90.6% vs. 67.7%, χ 2=26.916, P<0.001), mugwort (10.8% vs. 9.4% vs. 1.1%, χ 2=7.535, P=0.023), and ox-eye daisy (21.5% vs. 14.6% vs. 4.3%, χ 2=10.876, P=0.004) in allergic rhinitis combined with asthma group and allergic rhinitis group were significantly higher than those in allergic rhinitis group. The positive rates of D. pteronyssinus (96.2% vs. 84.0% vs. 53.5%, χ 2=46.343, P<0.001), D. farinae (96.2% vs. 81.5% vs. 48.8%, χ 2=52.756, P<0.001) and German cockroach (17.7% vs. 14.8% vs. 2.3%, χ 2=6.313, P=0.043) in > 6 years old group were significantly higher than those in > 3 years old group and > 3-6 years old group, while the sIgE positive rates of egg white (41.9% vs. 21.0% vs. 10.8%, χ 2=20.281, P<0.001) and milk (41.9% vs. 16.0% vs. 4.6%, χ 2=36.227, P<0.001) in ≤3 years old group were significantly higher than those in > 3-6 years old group and > 6 years old group. In addition, there were significant positive correlations between D. pteronyssinus and D. farinae, mugwort and ox-eye daisy, cat dander and horse dander, ox-eye daisy and dandelion, egg white and milk, timothy grass and sesame ( r s≥0.511, P < 0.01). With the increase of the class of house dust mite allergen, the sIgE positive rates of mugwort (0.0% vs. 1.5% vs. 10.8%, χ 2=9.714, P=0.008), ox-eye daisy (0.0% vs. 4.4% vs. 19.6%, χ 2=16.195, P<0.001), cat dander (0.0% vs. 7.4% vs. 18.2%, χ 2=11.459, P=0.003) and horse dander (0.0% vs. 1.5% vs. 15.5%, χ 2=15.443, P < 0.001) increased significantly, while the sIgE positive rate of milk (29.0% vs. 16.2% vs. 10.1%, χ 2=8.792, P=0.012) decreased significantly. Conclusions:Dust mite is the main allergen in children with respiratory allergic diseases in Guangdong, and ox-eye daisy is the main pollen allergen. The sensitization patterns of allergens varied in different ages and diseases, and children with respiratory allergic diseases should regularly detect allergens and pay attention to avoid them.

In China, the prevalence of allergic diseases is increasing, but allergy research and allergy diagnosis technologies are still in their infancy, posing certain hurdles to clinical diagnosis and treatment. The detection of allergen is essential for the prevention and treatment of allergic diseases. Clarifying the aetiology and risk factors of allergic diseases is critical in order to provide targeted environmental control and therapy for allergic diseases, as well as reduce patient pain and financial burden. In this study, allergen detection technologies and diagnosis strategies are described in order to provide direction for clinicians and laboratory technicians, improve allergic diseases diagnosis, and guide allergic disease therapy.

Objective:To investigate the common allergens in children with respiratory allergic diseases in Guangdong and provide the basis for preventing and treating respiratory allergic diseases.Methods:A total of 254 serum samples were collected retrospectively from children with allergic rhinitis and (or) asthma in the pediatric clinic of the First Affiliated Hospital of Guangzhou Medical University or Boai Hospital of Zhongshan City from August 2019 to August 2020 and tested positive for at least one allergens by ImmunoCAP 1000 or skin prick test. There were 173 males and 81 females, with a median age (interquartile interval) of 7 (4.00, 9.75) years. Specific IgE against eighteen common allergen were tested by magnetic particle chemiluminescence immunoassay. Statistical analysis using χ 2 test. Results:The positive rate of Dermatophagoides pteronyssinus (85.0%, 215/254) was the highest, followed by D. farinae (83.5%, 212/254), egg white (19.3%, 49/254), milk (14.6%, 37/254), German cockroach (14.2%, 36/254) and ox-eye daisy (12.6%, 32/254). Dust mites were the most common allergens in patients with allergic rhinitis / allergic asthma / allergic rhinitis and asthma. The positive rates of D. pteronyssinus (95.4% vs. 91.7% vs. 71.0%, χ 2=23.257, P<0.001), D. farinae (95.4% vs. 90.6% vs. 67.7%, χ 2=26.916, P<0.001), mugwort (10.8% vs. 9.4% vs. 1.1%, χ 2=7.535, P=0.023), and ox-eye daisy (21.5% vs. 14.6% vs. 4.3%, χ 2=10.876, P=0.004) in allergic rhinitis combined with asthma group and allergic rhinitis group were significantly higher than those in allergic rhinitis group. The positive rates of D. pteronyssinus (96.2% vs. 84.0% vs. 53.5%, χ 2=46.343, P<0.001), D. farinae (96.2% vs. 81.5% vs. 48.8%, χ 2=52.756, P<0.001) and German cockroach (17.7% vs. 14.8% vs. 2.3%, χ 2=6.313, P=0.043) in > 6 years old group were significantly higher than those in > 3 years old group and > 3-6 years old group, while the sIgE positive rates of egg white (41.9% vs. 21.0% vs. 10.8%, χ 2=20.281, P<0.001) and milk (41.9% vs. 16.0% vs. 4.6%, χ 2=36.227, P<0.001) in ≤3 years old group were significantly higher than those in > 3-6 years old group and > 6 years old group. In addition, there were significant positive correlations between D. pteronyssinus and D. farinae, mugwort and ox-eye daisy, cat dander and horse dander, ox-eye daisy and dandelion, egg white and milk, timothy grass and sesame ( r s≥0.511, P < 0.01). With the increase of the class of house dust mite allergen, the sIgE positive rates of mugwort (0.0% vs. 1.5% vs. 10.8%, χ 2=9.714, P=0.008), ox-eye daisy (0.0% vs. 4.4% vs. 19.6%, χ 2=16.195, P<0.001), cat dander (0.0% vs. 7.4% vs. 18.2%, χ 2=11.459, P=0.003) and horse dander (0.0% vs. 1.5% vs. 15.5%, χ 2=15.443, P < 0.001) increased significantly, while the sIgE positive rate of milk (29.0% vs. 16.2% vs. 10.1%, χ 2=8.792, P=0.012) decreased significantly. Conclusions:Dust mite is the main allergen in children with respiratory allergic diseases in Guangdong, and ox-eye daisy is the main pollen allergen. The sensitization patterns of allergens varied in different ages and diseases, and children with respiratory allergic diseases should regularly detect allergens and pay attention to avoid them.