The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Objective To investigate the factors influencing the positioning error of conical beam CT(CBCT)radiotherapy and the occurrence of acute radiation dermatitis in breast cancer fixed by cervical and thoracic integrated membrane in order to provide a basis for personalized out-target external boundary,selec-tion of fixed mode and guidance of radiodermatitis clinical practice work.Methods A total of 147 patients with breast cancer in this hospital from June 2022 to October 2023 were selected as the study subjects,inclu-ding 74 cases of breast conserving operation and 73 cases of modified radical(excision)operation.During the treatment period,CBCT scanning once a week obtained the image and conducted the grey match with the planned CT images to acquire the translational error of X(left and right),Y(head and foot)and Z(abdominal and dorsal)and the rotational posing error of X(pitch),Y(roll)and Z(yaw)axis,and at the same time,the acute radiodermatitis in nearly 3 months during radiotherapeutic period was recorded.Results Compared with the Z axis,the translation error of X axis and Y axis was greater,the rotation error was smaller,and the differ-ences were statistically significant(P＜0.05).The PTV external boundary of X,Y and Z axis calculated by the formula was 0.70,0.76,0.46 cm respectively.There was no statistically significant difference in the posi-tioning error of each direction of left and right breast between breast conservation operation and breast resec-tion operation(P＞0.05).The correlation between the age with X,Y and Z axis translation errors was-0.14,0.18 and 0.10 respectively,which of the age with X,Y and Z axis rotation errors was 0.12,＜0.01,0.02 respectively.The occurrence of grade 1 acute radiodermatitis in the patients with breast conserving oper-ation was 100.0％(74/74),which in the patients with excision operation was 13.7％(10/73),the occurrence of grade 2 was 82.2％,which of grade 3 was 4.1％(3/73),and the difference between them was statistically significant(P＜0.05).Conclusion In the every day positioning and target area external expansion,particular attention should be paid to the X and Y axis translational directions and the Z axis rotation direction.Using the integrated cervicothoracic thermoplastic membrane for fixing breast cancer is not affected by the operation mode,affected side position and age.

Objective: To investigate the reduction effect of hoding cricoarytenoid joint reduction with visual laryngoscope under intravenous anesthesia. Methods: The therapeutic effects of 40 patients with arytenoid dislocation(AD)treated by closed reduction in the single center from January 2020 to September 2021 were retrospectively analyzed, including 21 males and 19 females, median age 48 years. The etiology, symptoms, preoperative evaluation methods, reduction mode, reduction times, and the recovery of arytenoid cartilage movement and sound after reduction were evaluated and analyzed. Results: All patients had obvious hoarseness and breath sound before treatment. Under stroboscopic laryngoscope or electronic nasopharyngoscope, different degrees of vocal cord movement disorder and poor glottic closure can be seen. There were 28 cases of left dislocation, 9 cases of right dislocation and 3 cases of bilateral dislocation. The etiology of dislocation of cricoarytenoid joint: 25 cases (62.5%) of tracheal intubation under general anesthesia were the most common causes, was as follows by laryngeal trauma, gastroscopy, cough, vomiting and so on. Among them, 28 cases of reduction were initially diagnosed in our department, and 12 cases were diagnosed later after failure of reduction treatment. Of the 40 patients, 6 underwent reduction 24 hours after dislocation; 18 cases from 3 days to 1 month; 7 cases from 1 to 3 months; 6 cases were reset in 3~6 months; Over 6 months in 3 cases. After one reduction, 10 cases (10/40, 25%) recovered normal pronunciation, 14 cases (14/40, 35%) recovered normal pronunciation after two reduction, 10 cases (10/40, 25%) recovered normal pronunciation after three times, 2 cases (2/40, 5%) recovered normal pronunciation after four times, and 1 case (2.5%) recovered normal pronunciation after five times. Thin slice CT scan of larynx and cricoarytenoid joint reconstruction showed the types of AD: subluxation in 37 cases (92.5%) and total dislocation in 3 cases; 28 cases of left dislocation, 9 cases of right dislocation and 3 cases of bilateral dislocation; 29 cases (72.5%) had posterior dislocation and 11 cases (27.5%) had anterior dislocation. All patients were treated by intravenous anesthesia with arytenoid cartilage clamped by cricoarytenoid joint reduction forceps under visual laryngoscope. The curative effect was evaluated by stroboscopic laryngoscope and/or voice analysis at 1-2 weeks after operation. The vocal cord movement returned to normal and the pronunciation was good in 37 cases (92.5%). Conclusions: Hoding cricoarytenoid joint reduction with the vision laryngoscope under intravenous anesthesia is easy to operate and the reduction effect is more stable. It is a effective method for AD.
Anesthesia, Intravenous/adverse effects* ; Arytenoid Cartilage/injuries* ; Female ; Humans ; Intubation, Intratracheal/adverse effects* ; Joint Dislocations/therapy* ; Laryngeal Diseases/etiology* ; Laryngoscopes/adverse effects* ; Male ; Middle Aged ; Retrospective Studies

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

How to test the treatments of Chinese medicine (CM) and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM. For centuries, various approaches have been used to identify and measure the efficacy and safety of CM. However, the high-quality evidence related to CM that produced in China is still rare. Over the recent years, evidence-based medicine (EBM) has been increasingly applied to CM, strengthening its theoretical basis. This paper reviews the past and present state of CM, analyzes the status quo, challenges and opportunities of basic research, clinical trials, systematic reviews, clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China, pointing out how EBM can help to make CM more widely used and recognized worldwide.
Critical Pathways ; Evidence-Based Medicine ; Humans ; Medicine, Chinese Traditional ; Practice Guidelines as Topic ; Randomized Controlled Trials as Topic

Objective To explore the role of Notch signaling pathway in the matrix synthesis of osteoarthritis cartilage cell and its possi -ble mechanism.Methods Selected the femoral condylar cartilage of 8 patients who were admitted into our hospital and treated with knee joint replacement as the observation group,while the normal femoral condyle cartilage of one patient with above-knee amputation was selected as the control group.The specimens were given histological examination or cell isolation culture and detection.The cultured cells were divided into 4 groups,namely the normal cartilage cells,OA cartilage cells,OA cartilage cells with γ-secretase inhibitor DAPT,OA cartilage cells with recombinant human proteins Delta4.Then immunohistochemistry and Western blot were used for detecting the expression of Notch -1,Notch-3, Jagged-1,Jagged-2 and HES5 in chondrocytes in vitro.Results The expression of Notch signaling pathway and the phenotype of cartilage cells changed in the osteoarthritis.The expression of Notch-1,Jagged-1,Jagged-2 and HES5 were activated.γ-secretase inhibitor DAPT (20 μmol/L)could inhibit the expression of Notch-1,HES5,Jagged-1,and Notch-3,while it had no obvious effect on the expreesion of Jag-ged-2.Recombinant human proteins Delta 4(100 ng/μL)could promote the expression of Notch-1,Jagged-2,and HES5,and it had no obvi-ous effect on the expreesion of Jagged-1 and Notch-3.Conclusion The expression of Notch signaling pathway of cartilage cells changed in the osteoarthritis.DLL4 can activate the Notch signaling pathway and DAPT can inhibit the Notch signaling pathway.

There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.
Acute Radiation Syndrome ; blood ; immunology ; prevention & control ; Animals ; Blood Cells ; drug effects ; radiation effects ; Dose-Response Relationship, Drug ; Gamma Rays ; adverse effects ; Hydroxamic Acids ; therapeutic use ; Indoles ; therapeutic use ; Matrix Metalloproteinase Inhibitors ; therapeutic use ; Mice ; Radiation Injuries, Experimental ; blood ; immunology ; prevention & control ; Radiation-Protective Agents ; therapeutic use ; Spleen ; drug effects ; immunology ; radiation effects ; Survival Analysis ; Whole-Body Irradiation

Objective: To evaluate the clinical efficacy and safety of Qilin Pills in the treatment of oligoasthenospermia in infertile men. METHODS: This multi-centered randomized double-blind controlled clinical trial included 216 infertile males with oligoasthenospermia, 108 in the trial group and the other 108 in the control, the former treated with Qilin Pills at the dose of 6 g tid while the latter with Wuziyanzong Pills at 6 g bid, both for 12 weeks. We examined the total sperm count, sperm motility and the count of progressively motile sperm of the patients before and at 4, 8 and 12 weeks after medication and evaluated the safety of the drug based on the adverse events and the laboratory results of blood and urine routine examinations and liver and kidney function tests. RESULTS: Compared with the baseline, the patients in the trial group showed a significant time-dependent improvement after 4, 8 and 12 weeks of medication in sperm motility (21.75% vs 27.54%, 29.04% and 32.95%, P <0.05), total sperm count (156.27 ×106 vs 177.33, 188.18 and 205.44 ×106, P <0.05), and the count of progressively motile sperm (32.08 ×10⁶/ml vs 46.33, 50.98 and 61.10 ×10⁶/ml, P <0.05). The three parameters above were also improved in the controls, but more significantly in the trial group (P <0.05). CONCLUSIONS Qilin Pills can evidently improve the semen quality of oligoasthenospermia patients with no obvious adverse events.
Asthenozoospermia ; drug therapy ; Capsules ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Infertility, Male ; drug therapy ; Male ; Oligospermia ; drug therapy ; Semen Analysis ; Sperm Count ; Sperm Motility ; Treatment Outcome