This study was aimed at understanding the Babesia species makeup and distribution in small mammals in Jinsha River Basin of Yunnan Province,and the Babesia carriage status in small mammals in this area,to provide a scientific basis for the preven-tion and control of Babesia disease.A total of 1 493 small mammals belonging to 5 orders,10 families,25 genera,and 54 species were captured from 10 counties(cities)in the Jinsha River Basin of Yunnan Province in various agricultural and forest environments.DNA was extracted from liver and tick tissues,and 150 bp fragments of Babesia 18S rRNA were detected through molecular biological methods.The positive samples showed amplification of a 1 600 bp target fragment of 18S rRNA.Species characteristics were assessed through sequence comparison and phylogenetic analysis.A total of 14 small mammals infected with Babesia were detected in six coun-ties(cities)of Jinsha River Basin,Yunnan Province,with a positivity rate of 0.93%(14/1 493).The Otsu and Kobe types of Babesia voles were analyzed,and their sequences were compared with the sequences from human Babesia cases with high similarity and close evolutionary relationships.The positivity rates were 2.34%(3/128)in Qiaojia County,2.06%(2/97)in Yongshan County,1.88%(4/213)in Yuanmou County,1.03%(3/291)in Deqin County,0.95%(1/105)in Shangri-La City,and 0.78%(1/128)in Shuifu County.The positive small mammals belonged to one order,two families,six genera,and the following eight species:P.leucurus 5.56%(1/18),R.brunneusculus 3.36%(4/119),M.minutus 3.33%(1/30),E.custos 2.94%(1/34),N.confucianus 2.65%(3/113),N.fulvescens 2.35%(2/85),A.latronum 1.16%(1/86),and A.draco 0.98%(1/102).The detection of Babesia in M.minutus was re-poorted first time.Small animals infected with Babesia were detected in all three habitats and altitudes,and higher infection rates were observed in forest regions between 1 500 and 2 500 meters and high-altitude residential areas.Babesia infection was found in many small mammals in several counties(cities)along Jinsha River in Yunnan Province,and the epidemic status of Babesia in these areas warrants attention.

Objective:To preliminarily investigate the safety and efficacy of programmed death-1(PD-1)inhibitor combined with cord blood-derived natural killer cells(NK cells)in the treatment of advanced malignant solid tumors in an exploratory clinical trial.Methods:Three patients with advanced solid tumors treated at the Second Affiliated Hospital of Xi'an Medical University from December 2019 to December 2021 were enrolled.According to tumor type and CSCO guidelines,patients received multiple treatment cycles(21 days per cycle)consisting of standard chemotherapy,targeted therapy,or bevacizumab combined with PD-1 inhibitor.Umbilical cord blood-derived NK cells(8×107 cells per infusion)were infused at appropriate intervals during the treatment course.Target lesion size,tumor markers,levels of 12 peripheral blood cytokines,and lymphocyte subsets were assessed in each treatment cycle.Adverse events were also monitored throughout the treatment.Results:Following the treatment with PD-1 inhibitor combined with cord blood NK cells,2 patients achieved stable disease(SD,per RECIST 1.1 criteria),with durations of 118 days and 92 days,respectively.After NK cell infusion,patient#1 exhibited a marked decrease in the tumor marker CA199 to normal range and sustained for three follow-up periods;patient#2 showed significant reductions in tumor markers CA199,CA242,and CA724.Conclusion:The combination of NK cells with chemotherapy and PD-1 inhibitor demonstrates potential therapeutic efficacy for solid tumors.No severe immune-related adverse reactions were observed in the three patients enrolled in this study.

This study was aimed at understanding the Babesia species makeup and distribution in small mammals in Jinsha River Basin of Yunnan Province,and the Babesia carriage status in small mammals in this area,to provide a scientific basis for the preven-tion and control of Babesia disease.A total of 1 493 small mammals belonging to 5 orders,10 families,25 genera,and 54 species were captured from 10 counties(cities)in the Jinsha River Basin of Yunnan Province in various agricultural and forest environments.DNA was extracted from liver and tick tissues,and 150 bp fragments of Babesia 18S rRNA were detected through molecular biological methods.The positive samples showed amplification of a 1 600 bp target fragment of 18S rRNA.Species characteristics were assessed through sequence comparison and phylogenetic analysis.A total of 14 small mammals infected with Babesia were detected in six coun-ties(cities)of Jinsha River Basin,Yunnan Province,with a positivity rate of 0.93%(14/1 493).The Otsu and Kobe types of Babesia voles were analyzed,and their sequences were compared with the sequences from human Babesia cases with high similarity and close evolutionary relationships.The positivity rates were 2.34%(3/128)in Qiaojia County,2.06%(2/97)in Yongshan County,1.88%(4/213)in Yuanmou County,1.03%(3/291)in Deqin County,0.95%(1/105)in Shangri-La City,and 0.78%(1/128)in Shuifu County.The positive small mammals belonged to one order,two families,six genera,and the following eight species:P.leucurus 5.56%(1/18),R.brunneusculus 3.36%(4/119),M.minutus 3.33%(1/30),E.custos 2.94%(1/34),N.confucianus 2.65%(3/113),N.fulvescens 2.35%(2/85),A.latronum 1.16%(1/86),and A.draco 0.98%(1/102).The detection of Babesia in M.minutus was re-poorted first time.Small animals infected with Babesia were detected in all three habitats and altitudes,and higher infection rates were observed in forest regions between 1 500 and 2 500 meters and high-altitude residential areas.Babesia infection was found in many small mammals in several counties(cities)along Jinsha River in Yunnan Province,and the epidemic status of Babesia in these areas warrants attention.

Objective:To evaluate the clinical efficacy of nasal pedicle tissue flap based on nasal blood supply in the reconstruction of nasal skull base defects.Methods:A retrospective analysis was conducted on 138 clinical cases of skull base tumors and cerebrospinal fluid rhinorrhea treated at the Department of Otolaryngology, Head and Neck Surgery at Xiangya Hospital of Central South University from March 2017 to March 2023. A total of 79 males and 59 females were enrolled, aged from 8 to 82 years, with a median age of 51 years, including 108 patients (78.3%) with skull base tumors and 30 patients (21.7%) with cerebrospinal fluid rhinorrhea (and/or meningoencephalocele). During the surgery, 88 cases (63.8%) were repaired with nasal septal mucosal flaps pedicled with the posterior nasal septal artery, 14 cases (10.1%) with mucosal flaps pedicled with the anterior ethmoidal artery on the lateral wall of the nasal cavity, 6 cases (4.3%) with mucosal flaps pedicled with the posterior lateral nasal artery on the lateral wall and nasal floor, 12 cases (8.7%) with mucosal flaps pedicled with the anterior ethmoidal artery and posterior ethmoidal artery, and 18 cases (13.0%) with nasal septal mucosal extension flaps pedicled with the sphenopalatine artery or internal maxillary artery. Patients were followed up for 12 to 72 months postoperatively. Endoscopic examination or skull base enhanced MRI was performed to assess the growth and tumor recurrence in the skull base repair area. The t-test was used for statistical analysis.Results:Among 138 patients, primary repair was successful in 133 patients (96.4%), while 5 patients (3.6%) experienced postoperative cerebrospinal fluid rhinorrhea. These 5 patients all underwent nasal septal mucosal flap repair with the posterior nasal septal artery as the pedicle. Complications included 1 case of mucosal flap necrosis, 1 case of mucosal flap central perforation, and 3 cases of mucosal flap survival peripheral leakage, of which were all successfully treated with a second repair.Conclusion:The use of nasal pedicle mucosal flap based on nasal blood supply is a reliable, safe, and effective technique for repairing skull base defects.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective: To establish a triple-color pseudovirion-based neutralization assay (PBNA) and evaluate its capability of detecting immunogenicity of the sera generated by the immunization of HPV 9-valent vaccine. Methods: HPV pseudovirus (PsVs) 6/11/16/18/31/33/45/52/58 with the encapsidated fluorescence expressing red fluorescent plasmid N31-MCHREEY, green fluorescent N31-EGFP or blue fluorescent N31-mTagBFP were generated. The concentration of HPV PsVs and the infection titers of HPV PsVs were detected by double-antibody sandwich ELISA and TCID₅₀, respectively. The single- and triple color HPV 16/33/45 PsVs were used to detect the neutralization titers of mice sera immunized with HPV 9-valent vaccine and confirmed the accuracy and specificity of the triple-color PBNAs. Then, the single- and triple color HPV 6/11/18/31/33/45/52/58 PsVs were employed to detect the neutralization titers of cynomolgus macaques sera immunized with HPV 9-valent vaccine and determined whether the triple-color PBNAs could be applied to evaluate the immunogenicity of the sera generated by the immunization of HPV9-valent vaccine. Results: The concentration of HPV16 PsVs encapsulating green, red or blue fluorescent plasmid was 5.0 to 6.0 μg/ml and HPV6/11/18/31/33/45/52/59 triple-color HPV PsVs was about 1.0 to 3.0 μg/ml. 9 types HPV PsVs containing EGFP, Mcherry or mTagBFP reporter plasmid were obtained and the concentration can meet the need of neutralization detection. 9 types single-color fluorescent HPV PsVs had similar infectivity against 293FT cells with the infection titer values between 1×10⁴ and 1×10⁵. The results of PBNAs showed that there was no significant difference in the anti-HPV neutralization titers of mice sera induced by HPV 9-valent vaccine between single-color and triple-color HPV16/33/45 PsVs (P>0.05). Similarly, there was also no significant difference in the anti-HPV neutralization titers of cynomolgus macaques sera induced by HPV 9-valent vaccine between single-color and triple-color HPV6/11/18/31/33/45/52/58 PsVs (P>0.05). Conclusion We successfully established the triple-color PBNAs and verified the accuracy and specificity of triple-color PBNAs consistent with single-color PBNAs. The triple-color PBNAs can be applied to evaluate the immunogenicity of HPV 9-valent vaccine's immune serum.

Objective To investigate the effect of CYP3A5 and C5 gene polymorphisms on the concentration/dose ratio of tacrolimus in Chinese liver transplant patients during the early posttransplantation period.Methods A total of 100 adult patients who underwent primary liver transplantation (LT) were enrolled.Tacrolimus dosage and trough blood concentration were detemined at first week after liver transplantation.Two single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups.The relationship between gene polymorphisms and tacrolimus concentration/dose ratio (C/ D ratio) was analyzed.Results The distribution of allele A in C5 rs17611 was 63.5 ％ among donors and 58.5％ among recipients.For CYP3A5,the rs776746 allele G represented the major alleles in both donors and recipients (71％ and 72％,respectively).The tacrolimus C/D ratio of recipients carrying allele AA in C5 rs17611 was significantly higher than that of recipients carrying the C5 rs17611 allele G.Both donor and recipient CYP3A5 rs776746 polymorphisms were highly correlated with the tacrolimus C/D ratio at first week after liver transplantation.No linkage disequilibrium between CYP3A5 rs776746 and C5 rs17611 polymorphisms was found (D'max =0.392,r2max =0.034).Recipient CYP3A5 rs776746 allele A,C5 rs17611 genotype AA,and donor CYP3A5 rs776746 allele A were associated with rapid tacrolimus metabolism.With increasing number of these alldes,tacrolimus C/D ratio was reduced during the one week after transplantation.Conclusion Recipient C5 rs17611 polymorphism is a new genetic locus that influences tacrolimus metabolism in patients after OLT during the early post-transplantation periocd.

OBJECTIVE:To establish HPLC fingerprint for the leaves of Camptotheca acuminante in Guizhou.METHODS:HPLC method was performed.The determination was performed on Gemini-NX C18 column with mobile phase consisted of acetonitrile-0.2％ phosphoric acid (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 370 ran,and the column temperature maintained at 30 2.The sample size was 10 μtL.Using sorbitol as a reference,HPLC fingerprints of 14 batches of the leaves of C.acuminante were determined.The chromatographic fingerprint was analyzed with Similarity Evaluation System for Chromatographic Fingerprint of TCM (2004 A) in terms of common peak indentification,similarity evaluation and cluster analysis.RESULTS:There were 10 common peaks in HPLC fingerprints for 14 batches of the leaves of C.acuminate.And the similarity of 13 batches of the leaves of C.acuminate was greater than 0.90,and that of another one was less than 0.90.The leaves of C.acuminate were classified into 3 groups.CONCLUSIONS:The established fingerprint can provide reference for identification and quality evaluation of the leaves of C.acuminate.

As the urgent need of both clinic and research,the identification of hypertonia subtypes is becoming more and more important. Hypertonia assessment tool is a standardized discriminative measure with good reliability and validity. Hypertonia assessment tool can identify paediatric hypertonia subtypes. For its easily learning,it can be easily generalized in clinician.