Corona Virus Disease-2019 (COVID-19) has been among the major infectious events of the century. In today’s literature where COVID-19 and host factor effects are frequently examined, we aimed to examine another factor: Circadian Clock Protein PERIOD 3 (PER3). There is a significant correlation between PER3 gene polymorphism and circadian rhythm disturbances and immune system dysregulation.

In our study, we recruited 200 patients diagnosed with COVID-19 in our hospital between April–June 2020, and 100 volunteers without known comorbidities to create a healthy control group. After comparing the initial gene polymorphisms of the patients with healthy controls, three separate clinical subgroups were formed. Gene polymorphism distribution and statistical significance were examined in the formed patient groups.

No significant difference was found between the patient group and the healthy controls (P>0.05, for all). When patients were divided into two separate clinical subgroups as exitus/alive according to their last condition during their 28-day follow-up, the 4R/5R genotype was significantly more common in patients with a mortal course (P=0.007). The PER3 4R/5R genotype was found at a significantly higher rate in the group of patients with the need for intensive care (P=0.034).

The 4R/5R genotype may be associated with the need for intensive care and mortality in COVID-19 patients. These important results will be a guide for future studies.

The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. To explore the influencing factors on vaccine-induced effects, antibody responses to an inactivated SARS-CoV-2 vaccine in healthy individuals who were not previously infected by COVID-19 were assessed.

All subjects aged 18–60 years who did not have SARS-CoV-2 infection at the time of screening from June 19, 2021, to July 02, 2021, were approached for inclusion. All participants received two doses of inactivated SARS-CoV-2 vaccine. Serum IgM and IgG antibodies were detected using a commercial kit after the second dose of vaccination. A positive result was defined as 10 AU/mL or more and a negative result as less than 10 AU/mL. This retrospective study included 97 infection-naïve individuals (mean age 35.6 years; 37.1% male, 62.9% female).

The seropositive rates of IgM and IgG antibody responses elicited after the second dose of inactivated SARS-CoV-2 vaccine were 3.1% and 74.2%, respectively. IgG antibody levels were significantly higher than IgM levels (P<0.0001). Sex had no effect on IgM and IgG antibody response after the second dose. The mean anti-IgG level in older persons (⩾42 years) was significantly lower than that of younger recipients. There was a significantly lower antibody level at > 42 days compared to that at 0–20 days (P<0.05) and 21–31 days (P<0.05) after the second dose.

IgG antibody response could be induced by inactivated SARS-CoV-2 vaccine in healthy individuals (>18 years), which can be influenced by age and detection time after the second dose of vaccination.

Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD.

This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated.

By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity.

The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.

To study data about SARS-CoV-2 virus shedding and clarify the risk factors for prolonged virus shedding.

Data were retrospectively collected from adults hospitalized with laboratory-confirmed coronavirus disease-19 (COVID-19) in Wuhan Union Hospital. We compared clinical features among patients with prolonged (a positive SARS-CoV-2 RNA on day 23 after illness onset) and short virus shedding and evaluated risk factors associated with prolonged virus shedding by multivariate regression analysis.

Among 238 patients, the median age was 55.5 years, 57.1% were female, 92.9% (221/238) were administered with arbidol, 58.4% (139/238) were given arbidol in combination with interferon. The median duration of SARS-CoV-2 virus shedding was 23 days (IQR, 17.8–30 days) with a longest one of 51 days. The patients with prolonged virus shedding had higher value of D-dimer (P=0.002), IL-6 (P<0.001), CRP (P=0.005) and more lobes lung lesion (P=0.014) on admission, as well as older age (P=0.017) and more patients with hypertension (P=0.044) than in those the virus shedding less than 23 days. Multivariate regression analysis revealed that prolonged viral shedding was significantly associated with initiation arbidol >8 days after symptom onset [OR: 2.447, 95% CI (1.351–4.431)], ≥3 days from onset of symptoms to first medical visitation [OR: 1.880, 95% CI (1.035–3.416)], illness onset before Jan. 31, 2020 [OR: 3.289, 95% CI (1.474–7.337)]. Arbidol in combination with interferon was also significantly associated with shorter virus shedding [OR: 0.363, 95% CI (0.191–0.690)].

Duration of SARS-CoV-2 virus shedding was long. Early initiation of arbidol and arbidol in combination with interferon as well as consulting doctor timely after illness onset were helpful for SARS-CoV-2 clearance.

This paper proposes a new photoacoustic computed tomography (PACT) imaging system employing dual ultrasonic transducers with different frequencies. When imaging complex biological tissues, photoacoustic (PA) signals with multiple frequencies are produced simultaneously; however, due to the limited bandwidth of a single-frequency transducer, the received PA signals with specific frequencies may be missing, leading to a low imaging quality.

In contrast to our previous work, the proposed system has a compact volume as well as specific selection of the detection center frequency of the transducer, which can provide a comprehensive range for the detection of PA signals. In this study, a series of numerical simulation and phantom experiments were performed to validate the efficacy of the developed PACT system.

The images generated by our system combined the advantages of both high resolution and ideal brightness/contrast.

The interchangeability of transducers with different frequencies provides potential for clinical deployment under the circumstance where a single frequency transducer cannot perform well.

To explore a new artificial intelligence (AI)-aided method to assist the clinical diagnosis of tibial plateau fractures (TPFs) and further measure its validity and feasibility.

A total of 542 X-rays of TPFs were collected as a reference database. An AI algorithm (RetinaNet) was trained to analyze and detect TPF on the X-rays. The ability of the AI algorithm was determined by indexes such as detection accuracy and time taken for analysis. The algorithm performance was also compared with orthopedic physicians.

The AI algorithm showed a detection accuracy of 0.91 for the identification of TPF, which was similar to the performance of orthopedic physicians (0.92±0.03). The average time spent for analysis of the AI was 0.56 s, which was 16 times faster than human performance (8.44±3.26 s).

The AI algorithm is a valid and efficient method for the clinical diagnosis of TPF. It can be a useful assistant for orthopedic physicians, which largely promotes clinical workflow and further guarantees the health and security of patients.

Thrombosis in patients with atrial arrhythmias might be associated with remodeling of the left atrium (LA). We aimed to describe this relationship and identify a novel factor, in addition to the CHA₂DS₂-VASc score, to guide therapeutic strategies for preventing thromboembolism in the hope of improving the prognosis for such patients.

Patients diagnosed with atrial arrhythmias and who met our inclusion criteria were enrolled in this study. Various clinical parameters were recorded; diameters reflecting remodeling of the LA were measured and thrombosis was diagnosed by enhanced CT.

Totally, 192 patients were enrolled in the study. The overall prevalence of left atrial thrombosis was 8.3%. Patients with persistent atrial fibrillation exhibited the highest anteroposterior diameter of the LA (45.1±7.2 mm) and prevalence of thrombosis (15.6%). An anteroposterior LA diameter of ≥50 mm was a strong independent impact risk factor for thrombosis (OR=10.1, 95%CI: 2.8–36.9, P<0.001). The prevalence of LA thrombosis in patients with and without anteroposterior LA diameter of ≥50 mm was 25.8% and 5.0%, respectively.

Marked remodeling of the LA characterized by an anteroposterior LA diameter of ≥50 mm is a strong independent risk factor of thrombosis, and should be considered for the prevention of thromboembolism through various strategies.

Lymphatic endothelial cell (LEC) proliferation is essential for lymphangiogenesis. Hypoxia induces lymphangiogenesis, but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood. The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in hypoxia-repressed LEC proliferation.

Human dermal lymphatic endothelial cells (HDLECs) were cultured under normoxic or hypoxic conditions, and cell proliferation was determined using MTT or CCK-8 assays. CEACAM1 expression was silenced by siRNA transfection. Activation of mitogen-activated protein kinases (MAPKs) was examined by Western blotting and blocked by specific inhibitors.

Under hypoxia, HDLECs proliferation was suppressed and CEACAM1 expression was downregulated. Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia, suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation. In addition, silence of CEACAM1 increased phosphorylation of MAPK molecules: extracellular signal-regulated kinase (ERK), p38 MAPK and Jun N-terminal kinase (JNK) in HDLECs. However, only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence.

Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway, leading to inhibition of HDLEC proliferation. These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.

Autophagy is a programmed cell death procedure, which has essential functions in tumorigenesis. However, its temporal expression and function under different status are yet to be determined. This study aims to investigate the temporal expression of autophagy and its possible function in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal-pouch cancer model (HBPCM).

A total of 50 hamster buccal-pouch tumorigenesis models were established by painting DMBA for 4, 8, 10 and 13 weeks. The expression and subcellular localization of LC3, Beclin 1 and Bcl-2 in buccal lesions were evaluated by immunohistochemical staining and Western blotting. DNA damage was observed by immunohistochemical staining of 8-oHdG. The relationship between Beclin 1 and Bcl-2 was analyzed by immunofluorescence colocalization.

The expression levels of LC3 and Beclin 1 associated with autophagy in the experimental buccal pouch of HBPCM were significantly upregulated after 4 weeks (P<0.05), but gradually downregulated after 13 weeks of HBPCM induction. By contrast, the expression level of Bcl-2 was significantly upregulated after 13 weeks. The co-localized regions of Bcl-2 and Beclin 1 peaked after 4 weeks and then decreased gradually. The DNA damage in epithelial cells increased slightly after 4 weeks, and then rapidly decreased over the next 2 months.

Autophagy is motivated by a tumor suppressor that diminishes carcinogen-induced DNA damage. However, autophagy is gradually suppressed, which may be attributed to the interaction between Bcl-2 and Beclin 1. This result indicates that the promotion of autophagy may suppress malignant transformation and provide new insights on future potential treatments of HBPCM.

Primary biliary cholangitis (PBC) is a chronic progressive cholestatic liver disease. In recent years, researchers have found that cysteine-rich angiogenic inducer 61 (Cyr61, also known as CCN1) has a potential role in reducing portal inflammation in patients with PBC. This study aimed to explore the relationship between Cyr61 and PBC to provide new ideas and an experimental basis for the clinical treatment of PBC.

After induction of the overexpression of Cyr61 in a mouse model of PBC using recombinant adenovirus, hematoxylin and eosin staining and pathological scores were used to indicate intrahepatic inflammation and bile duct damage. Real-time PCR was used to detect changes in inflammation-related cytokines in the liver. To further study the mechanism, we assessed whether Cyr61 protects bile duct epithelial cells from cytotoxic effects.

Serum and hepatic Cyr61 levels were increased in the murine model of PBC. Overexpression of Cyr61 alleviated hepatic inflammation and bile duct injury in vivo. Cyr61 inhibited the cytotoxic effects of CD8⁺ T cells by acting on biliary epithelial cells (BECs) in vitro.

Our results provide novel insight into the pathogenesis of PBC and suggest that Cyr61 plays a dominant role in the cytotoxic effects on BECs in PBC. Consequently, therapeutic strategies targeting Cyr61 could be a potent therapy for PBC.

To explore the anti-inflammatory effect of the traditional Chinese medicine Zhikang capsule (ZKC) on lipopolysaccharide (LPS)-induced RAW264.7 cells.

Safe concentrations of ZKC (0.175, 0.35, and 0.7 mg/mL) were used after the half-maximal inhibitory concentration (IC₅₀) of RAW264.7 cells was calculated through the CCK-8 assay. In addition, the optimal intervention duration of ZKC (0.7 mg/mL) on RAW264.7 cells was determined to be 6 h, since all proinflammatory mediators [tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inteleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and monocyte chemotactic protein-1 (MCP-1)] had a decreasing tendency and relatively down-regulated mRNA expression levels as compared with other durations (4, 8, and 12 h). RAW264.7 cells were pretreated with ZKC at various concentrations (0.175, 0.35 and 0.7 mg/mL) for 6 h and then stimulated with LPS (1 µg/mL) for an additional 12 h.

In terms of inflammation, ZKC could reverse LPS-induced upregulation of TNF-α, IL-1β, IL-6, COX-2, iNOS, and MCP-1 at both the mRNA and protein levels in RAW264.7 cells in a dose-dependent manner. In terms of the NF-κB signaling pathway, ZKC could reduce phosphorylated p65 and promote M2 polarization of RAW264.7 cells under LPS stimulation in a dose-dependent manner. Moreover, ZKC exhibited a protective effect on macrophages from apoptosis.

ZKC exhibited obvious antiinflammatory and anti-apoptotic effects on LPS-induced RAW264.7 cells at the cellular level, and a weakened NF-κB signaling pathway may be a potential significant target.

MiRNAs have been recently implicated in the pathogenesis of ischemia-reperfusion (IR) injury. This study aimed to investigate the miRNA expression profiles in the early stages after lung transplantation (LT) and to study the involvement of the Toll-like receptor (TLR) signaling pathway in lung IR injury following LT.

We established the left LT model in mice and selected the miRNA-122 as a research target. The mice were injected with a miRNA-122-specific inhibitor, following which pathological changes in the lung tissue were studied using different lung injury indicators. In addition, we performed deep sequencing of transplanted lung tissues to identify differentially expressed (DE) miRNAs and their target genes. These target genes were used to further perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis.

A total of 12 DE miRNAs were selected, and 2476 target genes were identified. The GO enrichment analysis predicted 6063 terms, and the KEGG analysis predicted 1554 biological pathways. Compared with the control group, inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung wet/dry ratio (P<0.05). In addition, the activity of myeloperoxidase and the expression levels of tumor necrosis factor-alpha and TLR2/4 were decreased (P<0.05); whereas the expression of interleukin-10 was increased (P<0.05). Furthermore, the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway.

Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT. Of these, miRNA-122 promoted IR injury following LT, whereas its inhibition prevented IR injury in a TLR-dependent manner.

This study aimed to explore the orthographic processing of simplified Chinese characters in developmental dyslexic children in Kashgar, Xinjiang, China, and provide a theoretical basis for intervention strategies for developmental dyslexia in Chinese.

Using event-related potential (ERP) measures, 18 developmental dyslexic children and 23 typically developing children performed a character decision task with three types of stimuli: real characters (RCs), pseudocharacters (PCs), and noncharacters (NCs).

Behavioral results showed that the control children displayed a faster and higher accurate performance than the dyslexic children across PCs and NCs. ERP data revealed that the RCs and PCs elicited a stronger P200 than the NCs. Compared with the RCs and NCs, children in the control group showed more N400 negatives for PCs. It is worth mentioning that dyslexic children did not show any difference on N400, which reflected the insufficient orthographic processing of dyslexic children in China.

These results show that Chinese dyslexic children had orthographic processing defects.

Drug-induced sleep endoscopy (DISE) allows for the evaluation of dynamic airway collapse in patients with obstructive sleep apnea. However, a standardized sedation regimen for DISE is not yet available. This study aimed to investigate the safety profiles and efficacies of dexmedetomidine combined with butorphanol for DISE.

Sixty patients with obstructive sleep apnea scheduled to undergo DISE were randomly divided into Group D and Group DB. All recipients were initially given intravenous butorphanol (1 mg) (Group DB) or saline (Group D). Subsequently, both groups were sedated using a loading dose of 1.0 µg/kg/h of dexmedetomidine. Hemodynamic and respiratory parameters, the time to attain sufficient sedation, wakeup time, and adverse events during DISE were recorded.

Compared with Group D, the time until sufficient sedation and wakeup time in Group DB were significantly reduced. A higher performer satisfaction level was achieved in Group DB. Patients in Group DB showed a higher incidence of bradycardia compared with Group D. However, the bradycardia resolved spontaneously in both groups without any treatment. There was no instance of cough, hypotension, arrhythmia, nausea or vomiting in either group.

Compared to dexmedetomidine alone, a small dose of butorphanol infusion (1 mg) as an adjunct treatment to dexmedetomidine during DISE can reduce the dosage of dexmedetomidine, shorten the time until sufficient sedation and enhance the performer satisfaction level. This synergistic combination could be a promising sedation regimen for DISE in terms of procedural convenience and patient safety.