The polymorphism and thermostability of nirmatrelvir, the main antiviral component of the oral COVID-19 treatment drug, were studied. Four polymorphs of nirmatrelvir were prepared by recrystallization methods. Among them, Form 1 and nirmatrelvir methyl tert-butyl ether solvate (Form 2) had been reported in the literature, while nirmatrelvir isobutyl acetate solvate (NMTW-IBAC) and nirmatrelvir ethyl acetate solvate (NMTW-EA) are two new solvates. The crystal structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The thermostability of polymorphism and crystalline transformation were also investigated by combining Hirshfeld surface analysis and interaction energy analysis. The results showed that nirmatrelvir Form 1 belongs orthorhombic crystal system with the space group P2₁2₁2₁ and one nirmatrelvir molecule included in the asymmetric unit, which has the same crystal structure as nirmatrelvir Form 4 reported in the literature. Owing to its larger thermal expansion, the differences in crystallographic parameters obtained at different temperatures were found between Form 1 and Form 4. Three solvates of nirmatrelvir belonged to the iso-structural with monoclinic crystal system and the space group P2₁, in which the asymmetric unit contains one nirmatrelvir molecule and one solvent molecule. The thermal analysis results showed that nirmatrelvir Form 1 was a solvent-free crystal form with the best thermal stability and the strongest intermolecular hydrogen bonding. Among the three solvates, NMTW-EA has the worst thermal stability and the weakest hydrogen bonding interaction between the nirmatrelvir molecule and the solvent molecule. The energy framework of nirmatrelvir solvates showed that the closer the arrangement between solvent and nirmatrelvir molecules, the greater the total interaction energy between solvent and nirmatrelvir molecules. The phase transition studies of the three solvates showed that NMTW-IBAC and NMTW-EA were transformed into amorphous after desolvation, respectively, while Form 2 undergoes oiling during desolvation. The research provides theoretical guidance for the analysis, identification and quality control of nirmatrelvir polymorphs.

Objective To observe the changes in cardiopulmonary exercise test (CPET) variables of children with frequent premature ventricular contraction (PVC)before and after creatine phosphate treatment,to examine the difference of CPET results between PVC patients and healthy children,and to evaluate the effect of frequent PVC on the cardiac reserve function in children.Methods One hundred and nine frequent PVC children and 98 healthy children underwent treadmill exercise test and CPET respectively,the changes of CPET variables were observed among patients before and after treatment as well as among the healthy children.CPET variables include maximal oxygen consumption/kg (VO2max/kg),maximal oxygen consumption/heart rate( VO2max/HR),HR( at different time point),anaerobic threshold ( AT),and AT/VO2 maximum prediction (AT/VO2max pred).Results Before creatine phosphate treatment,VO2max/kg,VO2max/HR and AT/VO2max in frequent PVC children were ( 22.9±7.4 ) ml/( kg·min),( 9.3 ± 1.5 ) ml,( 15.5 ±2.7 ) ml/( kg· min).After creatine phosphate treatment,VO2 max/kg,VO2 max/HR and AT/VO2 max were (26.4 ± 6.0) ml/( kg· min),( 11.4 ± 3.3 ) ml,and ( 17.4 ± 3.8 ) ml/( kg· min).These CPET variables after creatine phosphate treatment in frequent PVC children were obviously higher than those before treatment and there was a significant difference [ VO2 max/kg ( t =2.11,P ＜ 0.001 ),VO2 max/HR ( t =4.02,P ＜ 0.001 ),AT( t =10.2,P ＜ 0.001 )].Control group of 98 healthy children had negative CPET results.Conclusion Cardiac reserve function decreases in frequent PVC children.After treatment,the exercise capacity and cardiac reserve function can be improved.CPET can reflect cardiac functional reserve changes in PVC children.

Objective To investigate the environmental impact of the Japanese Fukushima No.1 nuclear power plant accident on radiation levels in some areas of Liaoning province.Methods The emergent monitoring was performed by detecting atmosphere aerosols,precipitations,drinking water,vegetables,milk and seafood by gamma spectrometry analysis and gross activity measurements.Results The fission radionuclides of 131I,134Cs and 137Cs were detected in atmosphere aerosols 20 d after nuclear accident.The rad ionuclides of 131I,134Cs and 137Cs were found existing in atmosphere for 25,4 and 6 d,respectively,with the highest concentrations of 4.6 × 10 3,2.9 × 10-4 and 4.2 × 10-4 Bq/m3,respectively.The man-made fission radionuclides could not be detected in vegetablcs,drinking water and milk from Shenyang city and seafood from Dandong city.Conclusions The atmosphere might be slightly contaminated in Liaoning province due to the nuclear accident,whereas the vegetables,milk and drinking water not contaminated.

Objective To study the correlation of human cytomegalovirus infection with carotid atherosclerosis.Methods A total of 120 patients with carotid atherosclerosis and 140 healthy control patients were recruited for HCMV-PP65 antigen detection and Ultrasound examination.Results In carotid atherosclerosis and healthy patients,58.20％(71 cases)and 6.43％(9 cases)of the subjects were positive for HCMV-PP65 antigen(x2 =32.98,P ＜ 0.05).In carotid atherosclerosis group,69.01％(49 cases)of the patients with positive HCMV-PP65 antigen had instable plaques,while it was 47.06％(24 cases)in the patients with negative HCMV-PP65 antigen.The difference in the positivity of HCMV-PP65 between the two groups were significant(x2 =8.22,P ＜ 0.05).Conclusion Active infection of HCMV may be associated with Carotid Atherosclerosis and the plaques will be more instable.

This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.

AIM: To evaluate the safety of the laser peripheral iridoplasty ( LPIP ) for the early-stage chronic primary angle-closure glaucoma ( ECPACG) .
METHODS:Sixty-five eyes of 36 patients with ECPACG received LPIP. At preoperative and postoperative, patients were examined with intraocular pressure ( IOP ) , anterior chamber, optical coherence tomography ( OCT) , visual acuity, visual field, fundus and complications. The mean follow-up was 18. 2±6. 7mo (ranged 12~24mo).
RESULTS: The preoperative average IOP were 23. 8±5.6mmHg, postoperative 1wk, 1, 3, 6, 12mo and in the last follow-up time the average IOP were 18. 7±3. 8, 17. 9±3. 2, 17. 6±3. 5, 18. 4±3. 7, 18. 6±3. 7, and 18. 6±7. 8mmHg. There was statistical difference comparing with preoperative (P<0. 05, decreasing average 6. 5±3. 1mmHg compared with the preoperative, the difference was statistically significant (t=5. 32, P<0. 05). Postoperative 1wk, 1, 3, 6mo, the trabecular-iris angle ( TIA500 ) and the angle opening distance at 500μm ( AOD500 ) had the statistical difference comparing with preoperative ( P <0.05). At Postoperative 1a and the last follow-up time, the TIA500 and AOD500 did not have statistical difference comparing with preoperative (P>0. 05). The postoperative visual acuity, visual field, fundus had not changed. There were no complications found.
CONCLUSION:LPIP is safe, and has the short time effect in the treatment of ECPACG. With elapse of time, the effect of LPIP is weakened. We can repeat the treatment.

Objective Dendritic cell-associatedC-type lectin-1 ( Dectin-1) is one of the most important receptors in antifungal innate immune response.This study was to construct a recombinant adenovirus vector expressing themurine Dectin-1gene and acquire a high-concentration adenovirus by amplification and purification. Methods The PCR amplification product CLEC7A-pIRES2-EGFP was cloned into the intermediate vector pDONR221, and then recom-bined with the backbone vector pAD/CMV/V5-DEST to produce a re-combinant plasmid pAD-CLEC7A-pIRE2S -EGFP.The recombinant plasmid was linearized with Pac I and transfected into human embryon-ic kidney ( HEK293) cells to produce recombinant adenovirus pAD-CLEC7Ap-IRES 2-EGFP. The adenovirus was propagated in the HEK293 cells and purified by filtering through the cellulose acetate membrane and concentrating column.Fluorescence microscopy and re-al-time PCR were used to determine the expression of the Dectin-1 gene. Results PCR identification, enzyme digestion, and sequen-cing results manifested theDectin-1 gene in the vector, with the final adenovirus titer of 5×1011 IU/mL.Fluorescence microscopy revealed green fluorescence and real-time PCR assay confirmed that the expression of Dectin-1 was improved by 8677.25 times. Conclusion A relatively high-titer adenovirus expressing Dectin-1 was acquired,which may help to further study the high expression of Dectin-1 in anti-fungal innate immunity in vitro and in vivo.

We retrospectively analyzed the clinical manifestations,treatments and prognosis of infective endocarditis (IE)associated with renal lesions in children.There were 23 confirmed IE cases who were admitted to the Capital Institutes of Pediatrics from 1992 to 2012.There were 6 cases (26％) with renal lesions.Renal lesions included asymptonatic microscopic hematuria(1 case),asymptomatic proteinuria (1 case) and acute nephritic syndrome (4 cases).There were 3 cases of acute renal injury (AKI) resulted from nephritis accompanied with acute heart failure.The serum level of C3 was lower in patients with renal lesions than patients without renal lesions (P ＜ 0.05),but the clinical manifestations,physical signs and other laboratory findings were the same.Patients of both groups were treated with antibiotics.All patients were recovered and discharged.The average hospital days were (39.2-± 15.2)days for patients with renal lesions and (34.9-± 19.2) days for patients without renal lesions (P ＞ 0.05).Renal lesions secondary to IE are relatively common in IE patients in children.Most of renal lesions can be improved by effective antibiotics.Prognosis of those patients accompanying with AKI is bad.

BACKGROUND:S100B protein in patients with cardiac arrest, hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased. Ischemic brain injury may elevate the level of serum S100B protein and the severity of brain damage.METHODS:This article is a critical and descriptive review on S100B protein in serum after ischemic brain injury. We searched Pubmed database with key words or terms such as "S100B protein", "cardiac arrest", "hemorrhagic shock" and "ischemia reperfusion injury" appeared in the last five years.RESULTS:S100B protein in patients with cardiac arrest, hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased. Ischemic brain injury elevated the level of serum S100B protein, and the severity of brain damage.CONCLUSION:The level of S100B protein in serum is elevated after ischemic brain injury, but its mechanism is unclear.