Objective:To analyze the molecular epidemiological characteristics of norovirus (NoV) outbreaks in Qingdao.Methods:Anus swab specimens were collected during NoV outbreaks from 2016 to 2020 and detected by real-time RT-PCR. Full length of RNA-dependent RNA polymerase (RdRp) and VP1 gene were amplified by RT-PCR for sequencing, evolutionary analysis, and homology modeling.Results:A total of 65 NoV outbreaks were reported, with 59 outbreaks occurring in kindergartens and primary/secondary schools, showing a double peak epidemic pattern, with peaks occurring from March to May and from October to December. A GⅡ.P16 outbreak in Qingdao first appeared in March 2017 and became the predominant strains from 2017 to 2020(67.9%, 38/56), including two genotypes: GⅡ.2[P16] (97.4%, 37/38) and GⅡ.4 Sydney[P16] (2.6%, 1/38). The GⅡ.2[P16] strains isolated were closely related to the 2010-2012 GⅡ.2[P16] strains, from whichi they probably evolved. The GⅡ.2[P16] Qingdao strains shared five common substitutions, namely D173E (motif F), V175I (motif F), S293T, K357Q (motif D), and T360A (motif D). The RdRp nucleotide consistency between GⅡ.2[P16] and GⅡ.4 Sydney[P16] was greater than 95%, and there were mainly four amino acid differences, namely K54R, V125A, A312T, and K457R.The evolutionary variation of GⅡ.2[P16] VP1 was minimal, with only a few amino acid substitutions taking place. The main functional variations of GⅡ.4 Sydney[P16] VP1 included R297H (epitope A), D310N (NERK motif), D372N (epitope A), and R373H (positive selection site).Conclusions:GⅡ.P16 NoV is the predominant epidemic strain of ad norovirus outbreaks in Qingdao from 2016 to 2020, and continuous monitoring of its epidemic trend and in-depth study of its evolutionary mechanism are necessary.

Objective:To analyze the molecular epidemiological characteristics of norovirus (NoV) outbreaks in Qingdao.Methods:Anus swab specimens were collected during NoV outbreaks from 2016 to 2020 and detected by real-time RT-PCR. Full length of RNA-dependent RNA polymerase (RdRp) and VP1 gene were amplified by RT-PCR for sequencing, evolutionary analysis, and homology modeling.Results:A total of 65 NoV outbreaks were reported, with 59 outbreaks occurring in kindergartens and primary/secondary schools, showing a double peak epidemic pattern, with peaks occurring from March to May and from October to December. A GⅡ.P16 outbreak in Qingdao first appeared in March 2017 and became the predominant strains from 2017 to 2020(67.9%, 38/56), including two genotypes: GⅡ.2[P16] (97.4%, 37/38) and GⅡ.4 Sydney[P16] (2.6%, 1/38). The GⅡ.2[P16] strains isolated were closely related to the 2010-2012 GⅡ.2[P16] strains, from whichi they probably evolved. The GⅡ.2[P16] Qingdao strains shared five common substitutions, namely D173E (motif F), V175I (motif F), S293T, K357Q (motif D), and T360A (motif D). The RdRp nucleotide consistency between GⅡ.2[P16] and GⅡ.4 Sydney[P16] was greater than 95%, and there were mainly four amino acid differences, namely K54R, V125A, A312T, and K457R.The evolutionary variation of GⅡ.2[P16] VP1 was minimal, with only a few amino acid substitutions taking place. The main functional variations of GⅡ.4 Sydney[P16] VP1 included R297H (epitope A), D310N (NERK motif), D372N (epitope A), and R373H (positive selection site).Conclusions:GⅡ.P16 NoV is the predominant epidemic strain of ad norovirus outbreaks in Qingdao from 2016 to 2020, and continuous monitoring of its epidemic trend and in-depth study of its evolutionary mechanism are necessary.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

The preservation of anal sphincter function is an urgent demand for patients with distal rectal carcinoma who expect a good quality of life, especially for aged patients intolerant to surgery due to their poor physical conditions, always posing clinical challenges. Although the clinical complete response (cCR) rates of 24%-49% achieved by neoadjuvant chemoradiotherapy or total neoadjuvant therapy (TNT) allow partial patients to avoid or delay anal resection by adopting a wait-and-see strategy, they still face the risk of local recurrence. Studies have confirmed a dose-response relationship in radiotherapy for rectal cancer, with local doses ranging from 72 to 92 Gy potentially achieving a cCR rate of 50%. In contrast, the tolerated doses for conventional external beam radiotherapy (EBRT) vary between 45 and 54 Gy, while higher doses may cause severe damage to normal organs or tissues. Endorectal brachytherapy, characterized by direct irradiation of tumors, a short irradiation range, and rapid dose fall-off, increases local exposure dose while protecting surrounding organs and even the contralateral normal rectal mucosa. Two main modalities of endorectal brachytherapy are available: 50 kV contact X-ray therapy (CXB) and high-dose-rate brachytherapy (HDR-BT). This review summarizes and analyzes the latest advances in research on endorectal brachytherapy, demonstrating its association with higher cCR rates, long-term local control rates, and lower adverse reaction rates. Therefore, endorectal brachytherapy is a more beneficial alternative for aged patients with distal rectal carcinoma who are intolerant to surgery due to their poor physical conditions and require anal sphincter preservation.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective: To compare the clinical outcomes and biomechanical characteristics of 1-, 2-, and 3-level pedicle subtraction osteotomy (PSO), and establish selection criteria based on preoperative radiographic parameters. Methods: Patients undergone PSO to treat ankylosing spondylitis from February 2009 to May 2019 in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were enrolled. According to the quantity of osteotomy performed, the participants were divided into group A (1-level PSO, n = 24), group B (2-level PSO, n = 19), and group C (3-level PSO, n = 11). Clinical outcomes were assessed before surgery and at the final follow-up. Comparisons of the radiographic parameters and quality-of-life indicators were performed among and within these groups, and the selection criteria were established by regression. Finite element analysis was conducted to compare the biomechanical characteristics of the spine treated with different quantity of osteotomies under different working conditions. Results: Three-level PSO improved the sagittal parameters more significantly, but resulted in longer operative time and greater blood loss (p < 0.05). Greater stress was found in the proximal screws and proximal junction area of the vertebra in the model simulating 1-level PSO. Larger stress of screws and vertebra was observed at the distal end in the model simulating 3-level PSO. Conclusion Multilevel PSO works better for larger deformity correction than single-level PSO by allowing greater sagittal parameter correction and obtaining a better distribution of stress in the hardware construct, although with longer operation time and greater blood loss. Three-level osteotomy is recommended for the patients with preoperative of global kyphosis > 85.95°, T1 pelvic angle > 62.3°, sagittal vertical alignment > 299.55 mm, and pelvic tilt+ chin-brow vertical angle > 109.6°.

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.

Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Adenosine Triphosphate ; Animals ; Chemical and Drug Induced Liver Injury/etiology* ; Flavonoids ; Humans ; Inflammasomes ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein ; Nigericin