Objective To investigate the genetic characteristics of the VP1 region of Coxsackievirus A10 (CVA10) in Yunnan Province. Methods Fecal samples of suspected hand, foot and mouth disease (HFMD) were subjected to real-time fluorescent quantitative PCR for detection of enterovirus CVA10. Positive samples were subjected to VP1 gene sequence amplification and Sanger sequencing. Sequence splicing was performed with DNAstar7.1 Seqman software, and nucleotide sequence and amino acid site analysis were performed using Mega 6.0 software. Results The sequencing of VP1 gene of CVA10 obtained a sequence of 894 nucleotides, encoding 298 amino acids. Compared with the original strain, there were mainly three active amino acid mutation regions, 13-33, 141-142, and 283-285. The nucleotide difference rate between the Yunnan isolates and the reference strain ranged from 16.92% to 30.90%, and the amino acid difference rate ranged from 2.58% to 4.00%. C1 and C2 group nucleotide difference was 10.58%, and the amino acid difference rate was 1.80%. The VP1 150-176 region exhibited highly conserved characteristics. Six CVA10 strains and Sichuan strain MW178898 belonged to the C1 group of the C genotype. The other 14 CVA10 strains belonged to the C2 group. Conclusion VP1 gene mutation is active and CVA10 is an important pathogen of HFMD in Yunnan. C2 genotype of CVA10 is dominant in this study, and C1 and C2 have co-circulated in Yunnan. It is necessary to strengthen monitoring and develop multivalent vaccines containing CVA10 epidemic genotype.

Objective To evaluate the effect of follicular fluid(FF)exosomal miRNAs on follicular dysplasia in patients with polycystic ovary syndrome(PCOS)mediated by glycolysis pathway of granulosa cells(GCs),and to explore the mechanism. Methods Three PCOS infertile patients and three non-PCOS infertile patients were recruited. The baseline hormone levels of the two groups were measured before ovulation induction. The bilateral FF was obtained by puncture after short-acting and long-term ovulation induction,and the exosomes were collected by ultracentrifugation and identified by transmission electron microscopy. The total exosomal RNA was extracted by Trizol method to construct the library,which was compared to the reference genome GRCh38 for statistical analysis after miRNA sequencing and quality control processing. Clustering Profiler R package was used to implement GO annotation analysis and KEGG pathway analysis of the differentially expressed genes(DEGs),and Omnipath software for miRNAs interaction analysis. A total of 16 miRNA were randomly selected and detected by qPCR to verify the accuracy of the miRNA sequencing results. Results Compared with the non-PCOS group,luteinizing hormone(LH),anti-Muerian hormone(AMH),testosterone and antral follicle counts in PCOS group increased significantly(t = 2. 479 ～ 9. 163,each P < 0. 05). The exosomes of FF in both groups showed the cup-shaped vesicles with clear edge and light staining in the center,with the diameters of 100 — 150 nm and intact structure,and the concentration was about 8 × 1010particles/mL. A total of 928 miRNAs were detected by miRNA sequencing. Compared with the non-PCOS group,59 differentially expressed miRNA(DEmiRNA)were screened out in exosomes of POCS group,of which 31 were up-regulated and 28 were down-regulated. The differential trend of gene expression detected by qPCR was highly similar to that of miRNA sequencing. In FF exosomes of PCOS patients,the glycolysis efficiency and apoptosis of GCs were significantly changed by miRNA regulating mRNA. PKM,PFKL and HK2 were the key target genes for miRNA to regulate GCs glycolysis,and SLC2A1 was the key target gene for miRNA to regulate GCs apoptosis. Conclusion The miRNAs in FF exosomes of PCOS patients can weaken the glycolysis of GCs while accelerate the apoptosis,thus reducing the production of ATP and lactic acid,resulting in follicular dysplasia.

Objective: To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. Methods: This study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. Conclusion Positive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

ObjectiveTo adapt the Stanford Expectations of Treatment Scale（SETS） into Chinese（C-SETS） and test the feasibility， validity and reliability of its application in patients with diarrhea-predominant irritable bowel syndrome（IBS-D） with liver-constraint and spleen-deficiency syndrome treated with traditional Chinese medicine（TCM）. MethodsWe obtained authorisation from the developer of the SETS， and followed the principle of "two-way translation" to translate the SETS by literal translation and back translation to form the C-SETS. Ninety-six IBS-D patients with liver-constraint and spleen-deficiency syndrome were enrolled as respondents and filled out C-SETS before receiving treatment； the feasibility was assessed by the recall rate， completion rate and the duration of filling out the scale； the reliability was assessed by Cronbach's α； the structural validity was assessed by exploratory and confirmatory factor analysis， and the content validity was assessed by correlation analysis. ResultsThe C-SETS consists of 10 items， with the 1st， 3rd， and 5th rating items constituting the Positive Expectations subscale， and the 2nd， 4th， and 6th rating items constituting the Negative Expectations subscale， each of which is rated on a 7-point Likert Scale. The recall of C-SETS was 100%（96/96）， the completion rate was 89.58%（86/96）； Cronbach's α for the Positive and Negative Treatment Expectations subscales were 0.845 and 0.854， respectively； exploratory factor analysis showed that the coefficient of commonality for all six entries was larger than 0.4， and that the six entries could be used by both factors to explain 77.092% of the total variance； validation factor analysis showed that the goodness-of-fit index， comparative fit index， root mean square of approximation error， canonical fit coefficient， and chi-square degrees of freedom ratio took the values of 0.943， 1.003， 0， 0.943， and 0.626， respectively； and the results of Spearman's analysis suggested that the C-SETS had good content validity. ConclusionThe C-SETS has well feasibility， reliability， and validity， which initially proves that it can be used as a tool to assess the treatment expectation of patients with IBS-D with liver-constraint and spleen-deficiency syndrome before receiving TCM treatment.

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Objective:To investigate the conversion of stromal vascular fraction (SVF) in the microenvironment of radiation-induced skin injuries to provide guidance for clinical applications.Methods:Based on a random number table, C57BL/6N mice were categorized into four groups: the blank control, negative control, acute injury, and chronic injury groups, with each group containing 25 mice. The backs of mice in the blank control, acute injury, and chronic injury groups were exposed to 15 Gy X-ray irradiation. Then, the mice in the negative control, acute injury, and chronic injury groups were injected subcutaneously with the SVF derived from B6/G-R mice. The survival of these mice was observed 1, 3, 7, 14, and 21 d after the injection through fluorescence tracing and in vivo imaging. Accordingly, the clinical SVF injection regimens were optimized based on the experimental result of mice. Finally, local SVF injection was performed on different frequencies for patients in different wound conditions, with the efficacy being observed. Results:The fluorescence of SVF was observed from the tissue slices of the acute injury, chronic injury, and negative control groups 14 d post-injection. The result showed that the fluorescence intensity of SVF 1, 3, and 7 d post-injection was in the order of the negative control group > the acute injury group > the chronic injury group. The acute injury group ranked at the top and the chronic injury group remained at the bottom 14 d after the injection. The fluorescence of SVF in each group was barely detected 21 d after the injection. Compared to the negative control group, the acute injury group exhibited statistical differences only 14 d post-injection ( t = 4.11, P < 0.05), while the chronic injury group displayed statistical differences 1, 3, 7, and 14 d after the injection ( t = 3.88-5.74, P < 0.05). Furthermore, the acute injury group exhibited significantly higher fluorescence intensity of SVF than the chronic injury group ( t = 4.73-8.38, P < 0.05). The half-life of SVF for the negative control, acute injury, and chronic injury groups was 6.336, 6.014, and 2.163 d, respectively. As indicated by the application of SVF transplantation based on traditional surgical protocols in the clinical trial, SVF can significantly promote wound repair, with earlier SVF transplantation being more beneficial for wound healing. Conclusions:The conversion of SVF differs in the microenvironments of acute and chronic radiation-induced skin injuries. This can serve as an essential guide for the administration timing and injection frequency of SVF in clinical applications.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.

Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.

Objective:To investigate the regulatory role of RNA m 6A methyltransferase (METTL14) in ultraviolet B (UVB) radiation-induced skin injury, and to preliminarily explore the potential of targeted inhibition of METTL14 for treating UVB-induced skin injury. Methods:A UVB radiation-induced skin injury model was established by exposing C57BL/6J mice to 150 mJ/cm 2 UVB, and was assessed and scored with HE staining and Masson staining. UVB radiation-induced cell injury models were established by exposing human immortalized keratinocytes (HaCaT) and human skin fibroblasts (WS1) to 10 and 30 mJ/cm 2 UVB, respectively. The m 6A levels in the mouse skin and cell models after UVB exposure were quantified by colorimetric assay, and m 6A-related enzymes in cells were measured by Western blot. HaCaT and WS1 cell lines overexpressing METTL14 were constructed using recombinant adenoviral vectors, and the overexpression effects were tested by Western blot. The METTL14 overexpression cells were examined for their m 6A levels, proliferative abilities after UVB exposure (by clone formation assay), and changes in apoptosis (by flow cytometry). The model mice with UVB-induced skin injury in the treatment groups received subcutaneous injection of the METTL14 inhibitor S-adenosylhomocysteine (SAH) solution (1 mg/kg, 5 mg/kg) twice consecutively before and after irradiation; and the mice were assessed and scored for skin injury with HE staining and Masson staining. Results:On the 4th day after 150 mJ/cm 2 UVB irradiation, the mice showed remarkable skin injury, pathologically featuring inflammatory infiltration, tissue structure disorganization, and collagen fiber degradation, reaching the maximum score; and the m 6A level in the skin was significantly downregulated ( t = 3.07, P < 0.05). At 24 h after 10 and 30 mJ/cm 2 irradiation, HaCaT and WS1 cells showed significantly reduced survival rates ( t = 7.64, 7.15, P < 0.05), significantly downregulated m 6A levels ( t = 4.78, 4.36, P <0.05), and significantly time-dependent downregulation of METTL14 protein expression ( t = 6.39, 4.76, P < 0.05). In HaCaT and WS1 cells, METTL14 overexpression significantly up-regulated m 6A levels ( t = 7.66, 3.67, P < 0.05), significantly inhibited the clone-forming ability of cells after UVB irradiation ( t = 6.29, 3.84, P < 0.05), and significantly increased the rate of cell apoptosis ( t = 3.48, 9.54, P < 0.05). Compared with those in the normal saline group, the model mice with UVB-induced skin injury in the SAH treatment group (5 mg/kg) showed significantly decreased pathological scores of skin injury ( t = 3.21, 4.27, 5.81, P < 0.05), with milder inflammatory infiltration, more orderly tissue structure, and less collagen fiber degradation. Conclusions:METTL14 can increase the sensitivity of skin cells to UVB radiation, and targeted inhibition of METTL14 can effectively alleviate UVB radiation-induced skin injury, which may be a potential new target for the treatment of UVB radiation-induced skin injury.

Radon, the only natural radioactive gas, is also a primary source of natural radiation for human beings. Studies have revealed its diverse biological effects on the human body. This paper presents a summary of domestic and internal studies on radon conducted in recent years, organizing its impacts on various organs of the human body, along with their mechanisms and medical applications. Accordingly, novel reflections are proposed. This review aims to provide a theoretical basis for the in-depth interdisciplinary exploration into the impacts of radon on human health and their mechanisms in the future, holding great significance for preventing radon′s hazards and promoting its beneficial applications.