OBJECTIVE: Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351). METHODS: K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot. RESULTS: Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks. CONCLUSION These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals ; COVID-19/genetics* ; Mice ; Brain/metabolism* ; Apoptosis ; Mice, Inbred C57BL ; SARS-CoV-2/physiology* ; Pyroptosis ; Gene Expression Profiling ; Transcriptome ; Male ; Female

Objective:To investigate and analyze case reporting ethical review and patient informed consent reports published in the comprehensive journals of clinical medicine in China in 2022.Methods:According to the data from the 2022 Edition of the Chinese Science and Technology Journal of the Citation Reports(Extended Version),the case reports published in comprehensive journals of clinical medicine in 2022 were selected as the research objects.The information on ethics and patient informed consent was extracted from the case reports that met the selection criteria,and Microsoft Excel 2021 and SPSS 21.0 were used to sort out and analyze the data.Results:A total of 587 case reporting articles were published in the 42 included journals in 2022,of which 36(6.13%)reported on science and technology ethics and/or informed consent.Case reports reporting on science and technology ethics and/or informed consent mostly came from the key magazine of China technology(88.89%Vs.65.88%),and the proportion of manuscripts involving science and technology ethics on the official website of the journal was relatively high(86.11%Vs.63.88%),and the difference was statistically significant(P＜0.01).Conclusion:The proportion of case reports of science and technology ethics and/or informed consent in journals of comprehensive discipline classification of clinical medicine was relatively low.Currently,most international journals are required to obtain the informed consent of patients or legal guardians before publishing case reports.Compared with this,there are still certain gaps in China,which need to be paid great attention to.

Objective:To observe the efficacy and safety of ultra photon intense pulsed light combined with hydroquinone cream for the treatment of chloasma.Methods:From January 2020 to October 2022, a total of 30 patients with chloasma treated in the Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital, ranged from 28 to 54 years old with an average age of 39 years, were randomly divided into three groups with 10 patients in each group: combined treatment group was treated with ultra photon intense pulsed light combined with hydroquinone cream; ultra photon intense pulsed light group was treated with ultra photon intense pulsed light alone; hydroquinone group was treated with hydroquinone cream alone. The efficacy and safety of the three groups were compared after four months of treatment.Results:After the treatment, 10 cases were effective in the combined treatment group, 5 cases were effective in the ultra photon intense pulsed light group and 2 cases were effective in the hydroquinone group. The total effective rate of the combined treatment group was significantly better than that of the ultra photon intense pulsed light group and the hydroquinone group, with statistical significance ( P<0.05). The average melasma area severity index score of the three groups after treatment was significantly decreased compared with that before treatment respectively ( P<0.05), and the average melasma area severity index score of the combined treatment group after treatment was significantly lower than that of hydroquinone group, with statistical significance ( P<0.05). No serious adverse reactions were observed in all the patients. Conclusions:Ultra photon intense pulsed light and hydroquinone cream can improve chloasma alone, but ultra photon intense pulsed light combined with hydroquinone cream has better therapeutic effect.

OBJECTIVE: To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function. METHODS: A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated. RESULTS: After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05). CONCLUSION Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.
Humans ; Sleep Initiation and Maintenance Disorders/therapy* ; Estazolam ; Acupuncture Therapy ; Cognition ; Acupuncture Points ; Syndrome

OBJECTIVES: To summarize the open-eruption technique of impacted anterior maxillary teeth, this study reports a technically improved operation on surgical exposure based on dental follicles and evaluates post-treatment periodontal health considering the effect of dental follicles. METHODS: Patients who underwent open-eruption technique with unilateral labially impacted maxillary central incisors were selected. The impacted teeth were assigned to the experimental group, and the contralateral unimpacted maxillary central incisors were assigned to the control group. In the surgical exposure, the new technique makes use of dental follicles to manage the soft tissue, so as to preserve soft tissue for better aesthetic results and healthier periodontal tissue. Tooth length, root length, alveolar bone loss, and alveolar bone thickness were recorded after the therapy. RESULTS: A total of 17 patients with unilateral maxillary central incisor impaction were successfully treated. The tooth length and root length of the two groups showed a statistically significant difference between the impacted and homonym teeth, with a shorter length in the impacted tooth (P<0.05). More labial alveolar bone loss was found in the experimental group compared with that in the control group (P<0.05). The outcomes of the cementoenamel junction width, pa- latal alveolar bone loss, and alveolar bone thickness did not indicate statistical significance between the experimental and control groups (P>0.05). CONCLUSIONS In the surgical exposure, the new technique uses dental follicles to manage the soft tissue and preserve it for better aesthetic results and healthier periodontal tissues.
Humans ; Tooth, Impacted/surgery* ; Incisor ; Alveolar Bone Loss/diagnostic imaging* ; Tooth Root ; Dental Sac ; Maxilla/surgery* ; Esthetics, Dental

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.
Computational Biology/methods* ; Gene Expression Profiling/methods* ; Gene Regulatory Networks ; Humans ; Non-alcoholic Fatty Liver Disease/genetics* ; Protein Interaction Maps/genetics*

On the base of the paradigms of clinical studies on modern moxibustion by identifying the acupoint sensitization, the records of ancient literature in successive dynasties were collected on "identifying the sensitization" of acupoints in acupuncture. In association with acupoint detection of acupuncture recorded in current textbooks, a novel concept, "exerting acupuncture by identifying the acupoint sensitization" is proposed. Acupoint sensitization is the common initial link of effect achieved by both acupuncture and moxibustion. Hence, on the basis of the routine acupoint selection by differentiating syndrome, the state of acupoint must be considerably emphasized in either acupuncture or moxibustion. The clinical curative effect may be improved by selecting the sensitized points and identifying sensitization. This novel mode of diagnosis and treatment focuses on identifying acupoint sensitization by unifying acupuncture with moxibustion and in coincidence with the modern clinical characteristics of either acupuncture or moxibustion.
Acupuncture Points ; Acupuncture Therapy ; Moxibustion

OBJECTIVE: To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision. METHODS: In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients. RESULTS: The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively. CONCLUSION The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.
Humans ; Quality of Life ; Minimal Clinically Important Difference ; Treatment Outcome ; Constipation/therapy* ; Acupuncture Therapy

ObjectiveTo explore the predictive value of CT based radiomics model in differentiating Borrmann type Ⅳ gastric cancer （GC） from primary gastric lymphoma （PGL）. MethodsA total of 186 cases （Borrmann type Ⅳ GC： 132； PGL： 86） pathologically diagnosed by surgical resection and/or endoscopic biopsy were enrolled from June 2008 to April 2018 retrospectively. Radiomics features were extracted from CT arterial phase and venous phase images by computed algorithm， and selected by least absolute shrinkage and selection operator （Lasso） logistic regression， and then the CT-based radiomics models were established. CT subjective signs were reviewed to build CT subjective signs model， while CT subjective signs and radiomics signature were assembled to build combined model. The receiver operating characteristic （ROC） curve was used to evaluate the performance of CT subjective sign model， radiomics model and the combined model. ResultsTwo signs（the bright line sign of serosa and the irregular nodular protrusion on the serosa side）were selected into the CT subjective sign model. Among the radiomics features， 9 venous phase features， 8 arterial phase features and 14 arteriovenous combination features related to tumor classification were selected， and the corresponding radiomics models were constructed respectively. When the cut-off value of CT subjective sign model was 0.188， the area under curve （AUC） was 0.846， the sensitivity was 61.9%， the specificity was 81.7%， and the accuracy was 76.5%. The cut-off values of arterial phase， venous phase and arteriovenous phase radiomics model were -0.315， -0.669 and -0.858， respectively， and the AUCs were 0.864， 0.955 and 0.890， the sensitivity were 71.4%， 95.2% and 81.0%， the specificity were 85.0%， 88.3% and 80.0%， the accuracy were 81.5%， 90.1% and 80.3%， respectively. The cut-off values of arterial phase， venous phase and arteriovenous phase in the combined model were 0.257， 0.556 and 0.497， respectively， and the AUCs were 0.883， 0.956 and 0.918， the sensitivity was 71.4%， 90.5% and 71.4%， the specificity was 85.0%， 93.3% and 90.0% and the accuracy were 81.5%， 92.6% and 85.2%， respectively. The diagnostic performance of the models from high to low were the combined model， radiomics model and CT subjective finding model （ P< 0.001）， and CT venous phase images were more effective in the differential diagnosis of the two tumors. ConclusionsThe radiomics model based on the arterial and venous phases CT images could differentiate Borrmann type Ⅳ gastric carcinoma from primary gastric lymphoma effectively.

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*