Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

OBJECTIVES: To investigate the mechanism by which chitosan (CS) hydrogel loaded with human umbilical cord mesenchymal stem cell (HUVECs)-derived exosomes (hUCMSC-exos) (Exos@CS-Gel) improves diabetic wound healing. METHODS: hUCMSC-exos were extracted and Exos@CS-Gel was prepared. The effect of Exos@CS-Gel on proliferation and migration of HUVECs were evaluated using scratch wound assay and CCK-8 assay. Diabetic rat models with full-thickness skin wounds established by streptozotocin induction were randomized divided into 4 groups for treatment with Exos@CS-Gel (100 µg hUCMSC-exos dissolved in 100 µL 24% CS hydrogel), hUCMSC-exos (100 µg hUCMSC-exos dissolved in 100 µL PBS), CS hydrogel (100 µL 24% CS hydrogel), or PBS (control group). Wound healing and the therapeutic mechanisms were assessed using immunohistochemistry, HE staining, immunofluorescence, and qRT-PCR. RESULTS: In cultured HUVECs, Exos@CS-Gel treatment significantly promoted cell proliferation and migration. In the rat models of chronic diabetic wounds, the wound healing rate in Exos@CS-Gel group reached 92.7% on day 14, significantly higher than those in hUCMSC-exos group (9.12%), CS hydrogel group (16.28%), and control group (25.98%). Microvessel density and the expression levels of vascular endothelial growth factor and transforming growth factor β-1 were significantly increased in the Exos@CS-Gel group. CONCLUSIONS Exos@CS-Gel promotes survival capacity of hUCMSC-exos in vitro and accelerates diabetic wound healing in rats by promoting angiogenesis and cell proliferation.
Animals ; Wound Healing ; Humans ; Chitosan ; Exosomes ; Mesenchymal Stem Cells/cytology* ; Diabetes Mellitus, Experimental ; Rats ; Umbilical Cord/cytology* ; Hydrogels ; Human Umbilical Vein Endothelial Cells ; Cell Proliferation ; Rats, Sprague-Dawley ; Male

OBJECTIVE To observe the efficacy and safety of camrelizumab combined with pemetrexed and nedaplatin in the treatment of epidermal growth factor receptor （EGFR） and anaplastic lymphoma kinase （ALK） wild-type advanced non-squamous non-small cell lung cancer （NSCLC）. METHODS The data of 92 patients with EGFR/ALK wild-type advanced non-squamous NSCLC patients who visited the First Affiliated Hospital of Chongqing Medical University from August 2021 to May 2023 were collected and divided into nedaplatin group （46 cases） and carboplatin group （46 cases） based on different treatment regimens. Nedaplatin group was given camrelizumab for injection+nedaplatin for injection+pemetrexed disodium for injection； carboplatin group was given camrelizumab for injection+carboplatin injection+pemetrexed disodium for injection. Both groups received treatment with 21 days as one cycle， and all patients would be treated at least two cycles. The recent efficacy and the incidence of adverse drug reactions were observed in two groups， and the factors affecting progression-free survival （PFS） of patients were analyzed. RESULTS There was no statistically significant difference in the objective response rate， disease control rate， median PFS， and the incidence of grade 3-5 treatment-related adverse event （TRAE） between the two groups （P＞0.05）. While the incidence of grade 1-2 renal and urinary system TREA， palpitations and pericardial effusion in nedaplatin group were significantly lower than carboplatin group， the incidence of nausea， vomiting and decreased appetite were significantly higher than carboplatin group （P＜0.05）. The patient’s gender， age， smoking history， Eastern United States Cancer Collaboration score， and TNM staging were not significant factors affecting patient’s PFS （P＞0.05）. CONCLUSIONS Camrelizumab combined with pemetrexed and nedaplatin has significant efficacy in the treatment of EGFR/ALK wild-type advanced non-squamous NSCLC， with good safety.

Objective:To analyze the relationship between CT attenuation value of pulmonary artery thrombi and the efficacy of interventional thrombolysis in patients with acute pulmonary embolism (APE).Methods:This was a single center cross-sectional study. The clinical and imaging data of 89 APE patients who underwent interventional thrombolysis in Affiliated Hospital of Xuzhou Medical University from January 2018 to December 2022, were retrospectively analyzed. All patients underwent CT pulmonary angiography (CTPA) before and after thrombolysis, the CT attenuation value of pulmonary artery thrombi and ratio of CT attenuation value of thrombi to left subscapularis muscle CT value were obtained; and the difference of Qanadli embolism index (ΔQ) before and after thrombolysis was calculated. According to the median ΔQ, patients were classified as good efficacy group (ΔQ>50%) and poor efficacy group (ΔQ≤50%). The clinical characteristics and quantitative parameters of CT were compared between the two groups, and the factors associated with efficacy of thrombolysis were analyzed with univariate and multivariate logistic regression. The correlation between CT attenuation value of pulmonary artery thrombi and ΔQ was analyzed by Spearman correlation analysis.Results:The CT attenuation value of thrombi and ratio of attenuation value of thrombi to left subscapularis muscle CT value showed significant difference between the two groups ( P<0.05). Multivariate analysis showed that compared with CT attenuation value of emboli≤53.47 HU, the value>53.47 HU might be associated with the good efficacy of thrombosysis ( OR=9.175, 95% CI: 0.937-89.846, P=0.057). There was a positive correlation between CT value of pulmonary artery thrombi and ΔQ ( r=0.365, P<0.001). Conclusion:The CT attenuation value of thrombi can predict the efficacy of interventional thrombolysis in APE patients, and patients with higher CT attenuation value would have a better treatment response.

AIM To investigate the effects of Xinyue Capsules on the expression of glycerophospholipid metabolizing enzymes in isoproterenol(ISO)-induced rat heart tissue and primary myocardial cells of neonatal rats.METHODS The SD rats were randomly divided into the normal group,the model group,the Xinyue Capsules intervention group and Xinyue Capsules control group,with 8 rats in each group.The rat model of cardiac hypertrophy was established by 14 days consecutive intraperitoneal injection of ISO(30 mg/kg).Prior to the modeling,once daily administration of 0.393 g/kg Xinyue Capsules was given by gavage from 3 days in advance to the end of the experiment.After the last administration,the procurement of blood from abdominal aorta,the left and right ventricles were processed.And the rats had their indices levels of the heart,the left ventricle and the right ventricle measured;their pathomorphological changes of myocardial tissue observed using HE staining;their expressions of cardiac hypertrophy-related myocardial embryonic genes ANP,β-MHC and α-SKA mRNA detected using RT-qPCR method;and their serum TC,TG,LDL-C and HDL-C levels detected by biochemical method.In in vitro experiment,the neonatal rat model of myocardial hypertrophy was induced by exposure to ISO 1 μmol/L for 24 h.The investigation of the effect of Xinyue Capsules 12.5 μg/mL on ISO-induced myocardial hypertrophy was conducted by detection of myocardial cell area,embryo genes related to cardiac hypertrophy and myocardial cells protein cuntent.The further anti-cardiac hypertrophy mechanism of Xinyue Capsules research was conducted using RT-qPCR and Western blot to detect the gene and protein expressions of phospholipase A2(PLA2G6),phospholipase A1 member A(PLA1A)and lecithin cholesterol acyltransferase(LCAT)in left ventricle tissue and myocardial cells of each group.RESULTS The in vivo experimental result showed that compared with the normal group,the model group displayed increased indices levels of the heart,the left ventricle and the right ventricle and cross-sectional area of left ventricular myocytes(P＜0.05);and up-regulated expressions of ANP,β-MHC,α-SKA mRNA and PLA2G6,PLA1A and LCAT mRNA and proteins in the left ventricle(P＜0.05);and increased levels of serum TC,TG and LDL-C(P＜0.05);and decreased HDL-C level(P＜0.05).However,the intervention of Xinyue Capsules inhibited the changes of the aforementioned indices(P＜0.05).The in vitro experimental result revealed that Xinyue Capsules inhibited the ISO-induced increases of myocardial cell surface area and myocardial cell protein level,the up-regulation of ANP,β-MHC,α-SKA mRNA expressions and the PLA2G6,PLA1A,LCAT mRNA and protein expressions as well(P＜0.05).CONCLUSION Xinyue Capsules can improve the ISO-induced cardiac hypertrophy in rats,and its mechanism may be associated with its regulation upon the expressions of glycerophospholipid metabolism-related enzymes PLA2G6,PLA1A and LCAT.

Objective To understand the basic characteristics of Rickettsia bacteria carried by parasitic ticks on the surface of free-range goats in the mountainous areas of Luodian County, Guizhou Province. Methods Ticks were collected from the free-range goats raised in the mountainous areas of Luodian County, Guizhou Province, China. DNA was extracted from individual ticks to prepare pooled DNA samples for full-length 16S rRNA sequencing. Quality-controlled sequences were annotated and classified using the Kraken2 database. The best-quality sequence for each species was selected as the representative sequence, and the consistency of each obtained representative sequence with Rickettsia sequences was assessed using the Basic Local Alignment Search Tool (BLAST) on the National Center for Biotechnology Information (NCBI) website to evaluate the identity of the obtained representative sequence with the Rickettsia sequence. Based on the results of the genetic consistency analysis, the representative sequence with the highest consistency with registered Rickettsia genes on NCBI and other sequences of the same Rickettsia species were selected, then, using the Orientia within the family Rickettsiaceae as the outgroup to construct the phylogenetic tree by MEGA 7.0 software. Results　A total of 66 ticks were collected, of which 63 were Haemaphysalis longicornis and 3 were Rhipicephalus microplus. A total of 499 representative sequences were obtained in this study. BLAST analysis revealed that 21 representative sequences had more than 85% gene identity with 16S rRNA genes of Rickettsia in the NCBI nucleotide database. Among them, 9 sequences were more than 89% gene identity to Rickettsia (KU758903 and KY433580) isolated in China, with OTU47 showing the highest consistency at 95.76% with KU758903. Six sequences were more than 90% identity to the genes of Rickettsia (LC388776 and MT434769) isolated in China and Japan; three sequences were more than 89% identity to the genes of Rickettsia symbionts (KY617772) isolated in Henan Province, China; two sequences had more than 85% genetic identity with Rickettsia japonica (MF496167 and MF496155) isolated in Shandong Province, China; one sequence had more 85% genetic identity with Rickettsia vini isolated in Belgium. Phylogenetic analysis suggests that Rickettsia (OTU47) identified in this study belongs to the same branch as an unidentified Rickettsia species isolated in China (GenBank accession number: KU758903) and is closely related to Rickettsia longicornis isolated in Yunnan, China (GenBank accession number: KY433580).Conclusions The ticks parasitizing free-range goats in Luodian County, Guizhou, carry mostly unidentified Rickettsia species, and their pathogenicity and public health significance need to be further studied.

OBJECTIVES: This study aimed to investigate the clinical characteristics of congenital deciduous teeth absence and its permanent teeth performance type by using panoramic radiographs. METHODS: A total of 15 749 panora-mic radiographs of 3-6-year-old children with deciduous dentition were collected from January 2020 to December 2021. The incidence of congenital deciduous teeth absence was observed, and the abnormality of permanent teeth was recor-ded. SPSS 24.0 software was used for statistical analysis. RESULTS: The incidence of congenital deciduous teeth absence was 2.54% (400/15 749), which was found in 217 girls and 183 boys, and the difference between the genders was statistically significant (P=0.003). The absence of one and two deciduous teeth accounted for 99.75% (399/400) of the subjects. In addition, 92.63% (490/529) of mandibular deciduous lateral incisor was congenitally absent, 44.80% (237/529) of deciduous teeth was absent in the left jaw, and less than 55.20% (292/529) was absent in the right; the difference between them was statistically significant (P=0.017). The absence of 96.41% (510/529) deciduous teeth in the mandibular was significantly more than that of 3.59% (19/529) in the maxillary, and the difference between was statistically significant (P=0.000). Furthermore, 68.00% (272/400) and 32.00% (128/400) of deciduous teeth were absent in unilateral and bilateral, respectively, and the difference was statistically significant (P=0.000). Four types of congenital deciduous teeth absence with permanent teeth were observed as follows: 1) 73.91% (391/529) of permanent teeth was absent; 2) 20.60% (109/529) of permanent teeth was not absent; 3) the number of fused permanent teeth accounted for 4.91% (26/529); 4) the number of supernumerary teeth was 0.57% (3/529). CONCLUSIONS Although the absence of congenital deciduous teeth is less common than that of permanent teeth, it affects deciduous and permanent teeth to some extent. Dentists should pay attention to trace and observe whether abnormalities are present in the permanent teeth and take timely measures to maintain children's oral health.
Male ; Female ; Humans ; Tooth, Deciduous ; Dentition, Permanent ; Tooth, Supernumerary/epidemiology* ; Anodontia/etiology* ; Tooth Abnormalities/complications* ; Fused Teeth/epidemiology*

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype