BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

Objective:To investigate the clinical efficacy of mifepristone pretreatment combined with delayed hysteroscopic surgery for retained products of conception(RPOC)complicated with enhanced myometrial vascu-larity(EMV),aiming to reduce intraoperative bleeding risk and improve patient outcomes.Methods:A retrospec-tive analysis was conducted on clinical data from 65 RPOC patients with EMV treated between June 2014 and June 2024.Patients were divided into an observation group(mifepristone pretreatment+hysteroscopic surgery,n=34)and a control group(hysteroscopic surgery alone,n=31)based on treatment approach.Patients in the observation group received oral mifepristone(25 mg/d)preoperatively until beta-human chorionic gonadotropin(β-hCG)decreased by≥50％or treatment reached 30 days,with surgery performed when β-hCG fell to<200 U/L or EMV area shrank by>50％.Intraoperative blood loss,operation time,reduction in β-hCG levels,degree of EMV regression,and surgical complication rates were compared between the two groups.Results:Intraoperative blood loss was significantly lower in the observation group than in the control group(20.0 ml vs.40.0 ml,P<0.05),op-eration time was shorter(27.38±8.00 min vs.35.45±8.50 min,P<0.05),and transfusion rate was lower(2.94％vs.19.35％,P<0.05).At 2 weeks postoperatively,both the reduction in β-hCG levels(1395.17 U/L vs.276.56 U/L,P<0.05)and the degree of EMV regression(11.6 cm2 vs.5.0 cm2,P<0.05)were significantly bet-ter in the observation group,with effect sizes quantified as large(Cohen's d=1.85)and very large(Cohen's d=3.47),respectively.The incidence of severe complications(Grade Ⅱ+Ⅲ)was significantly lower in the observa-tion group(2.94％vs.22.58％,P<0.05),but the reintervention rate showed no statistical difference(2.94％vs.12.90％,P=0.299).Conclusions:Mifepristone pretreatment creates safer conditions for hysteroscopic surgery by reducing β-hCG levels and shrinking the EMV area.It significantly reduces intraoperative bleeding,shortens op-eration time,and lowers the incidence of severe complications,making it an effective treatment strategy for RPOC patients complicated with EMV.

Objective:To investigate the clinical efficacy of mifepristone pretreatment combined with delayed hysteroscopic surgery for retained products of conception(RPOC)complicated with enhanced myometrial vascu-larity(EMV),aiming to reduce intraoperative bleeding risk and improve patient outcomes.Methods:A retrospec-tive analysis was conducted on clinical data from 65 RPOC patients with EMV treated between June 2014 and June 2024.Patients were divided into an observation group(mifepristone pretreatment+hysteroscopic surgery,n=34)and a control group(hysteroscopic surgery alone,n=31)based on treatment approach.Patients in the observation group received oral mifepristone(25 mg/d)preoperatively until beta-human chorionic gonadotropin(β-hCG)decreased by≥50％or treatment reached 30 days,with surgery performed when β-hCG fell to<200 U/L or EMV area shrank by>50％.Intraoperative blood loss,operation time,reduction in β-hCG levels,degree of EMV regression,and surgical complication rates were compared between the two groups.Results:Intraoperative blood loss was significantly lower in the observation group than in the control group(20.0 ml vs.40.0 ml,P<0.05),op-eration time was shorter(27.38±8.00 min vs.35.45±8.50 min,P<0.05),and transfusion rate was lower(2.94％vs.19.35％,P<0.05).At 2 weeks postoperatively,both the reduction in β-hCG levels(1395.17 U/L vs.276.56 U/L,P<0.05)and the degree of EMV regression(11.6 cm2 vs.5.0 cm2,P<0.05)were significantly bet-ter in the observation group,with effect sizes quantified as large(Cohen's d=1.85)and very large(Cohen's d=3.47),respectively.The incidence of severe complications(Grade Ⅱ+Ⅲ)was significantly lower in the observa-tion group(2.94％vs.22.58％,P<0.05),but the reintervention rate showed no statistical difference(2.94％vs.12.90％,P=0.299).Conclusions:Mifepristone pretreatment creates safer conditions for hysteroscopic surgery by reducing β-hCG levels and shrinking the EMV area.It significantly reduces intraoperative bleeding,shortens op-eration time,and lowers the incidence of severe complications,making it an effective treatment strategy for RPOC patients complicated with EMV.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.

Objective:To investigate the prenatal management for pathogenic copy number variation (CNV) by analyzing the parental origin of CNV and pregnancy outcomes in 56 pedigrees.Methods:This study retrospectively analyzed the information of patients who received interventional prenatal diagnosis and chromosomal microarray analysis (CMA) at Guangzhou Women and Children's Medical Center from January 2015 to December 2020. The cases with pathogenic CNV indicated by CMA and receiving parental CMA for further verification were finally enrolled. Clinical data including prenatal diagnostic indications, chromosomal distribution of the pathogenic fragments and fragment sizes were collected and analyzed using t test. All cases were followed up by telephone and record review. Results:Fifty-six cases were included in this study. Pathogenic CNV in 13 (23.2%, 13/56) fetuses were inherited from one parent (eight from mothers and five from fathers), and mainly located in chromosomes 22 (3/13), 17 (3/11), 16 (2/7), 1 (2/4), and X (3/6) with fragment sizes all less than 3 Mb. The fragment size of inherited pathogenic CNV was significantly smaller than that of de novo CNV [1.69 (1.36-2.22) vs 7.54 (2.11-12.30) Mb, t=3.47, P=0.001]. Among the 43 cases with de novo pathogenic CNV, seven (16.3%) were lost to follow up and 35 (97.2%) terminated the pregnancy. The other one with a 0.58 Mb microruplication at 16p11.2 indicated at 37 gestational weeks gave birth to a baby weighting 2 900 g at 39 gestational weeks and no abnormalities were reported during an eight-month telephone follow-up. Two out of the 13 cases with inherited pathogenic CNV were lost to follow up and six pregnancies were terminated. The other five pregnancies were continued and babies were delivered with no abnormalities during a median follow-up period of 13 (4-15) months. Conclusion:Pathogenic CNV alone should not be the indication for pregnancy termination.

Objective:To investigate the clinical effect of medial plantar flap combined with free groin flap in the reconstruction of heel defect.Methods:The patients with heel skin and soft tissue defects admitted to the Department of Burns & Plastic and Hand & Foot Surgery of Yulin No.2 Hospital from October 2015 to December 2020 were retrospectively analyzed. After emergency debridement, a plantar medial island flap was used to repair the foot heel defect, a free groin flap was used to repair the medial plantar donor site, and the groin donor site was closed primarily. Postoperatively routine anti-infection, spasmolysis, anticoagulation, expanding treatment were performed after the procedure. The blood supply, survival of the flap, and the healing of the donor area of the flap were observed. The shape and function of the heel were observed in follow-up.Results:Eight patients were enrolled, including 7 males and 1 female, aged from 20 to 71 years, with an average of 32.2 years. There were 5 cases of heel trauma, 1 case of heel squamous cell carcinoma, 1 case of heel frostbite, and 1 case of heel ulcer. The wound area of the heel was 4 cm×3 cm-7 cm×6 cm. The surgical procedure was smooth, and the incision range of the heel island flap and groin flap was 0.5-1.0 cm larger than that of the heel wound. All 8 patients had primary healing after the operation. Follow-up for 3-12 months showed that all patients were satisfied with heel shape, sensory function and walking function. There was no depression, scar hyperplasia, and contracture in the medial plantar donor area, and no local skin ulcer. There is only a linear scar in the groin donor area.Conclusions:Medial plantar island flap combined with a free groin flap can repair the defect of the heel, and the affected foot has good healing, certain sensory function, and satisfactory curative effect.

Objective:To investigate the clinical effect of medial plantar flap combined with free groin flap in the reconstruction of heel defect.Methods:The patients with heel skin and soft tissue defects admitted to the Department of Burns & Plastic and Hand & Foot Surgery of Yulin No.2 Hospital from October 2015 to December 2020 were retrospectively analyzed. After emergency debridement, a plantar medial island flap was used to repair the foot heel defect, a free groin flap was used to repair the medial plantar donor site, and the groin donor site was closed primarily. Postoperatively routine anti-infection, spasmolysis, anticoagulation, expanding treatment were performed after the procedure. The blood supply, survival of the flap, and the healing of the donor area of the flap were observed. The shape and function of the heel were observed in follow-up.Results:Eight patients were enrolled, including 7 males and 1 female, aged from 20 to 71 years, with an average of 32.2 years. There were 5 cases of heel trauma, 1 case of heel squamous cell carcinoma, 1 case of heel frostbite, and 1 case of heel ulcer. The wound area of the heel was 4 cm×3 cm-7 cm×6 cm. The surgical procedure was smooth, and the incision range of the heel island flap and groin flap was 0.5-1.0 cm larger than that of the heel wound. All 8 patients had primary healing after the operation. Follow-up for 3-12 months showed that all patients were satisfied with heel shape, sensory function and walking function. There was no depression, scar hyperplasia, and contracture in the medial plantar donor area, and no local skin ulcer. There is only a linear scar in the groin donor area.Conclusions:Medial plantar island flap combined with a free groin flap can repair the defect of the heel, and the affected foot has good healing, certain sensory function, and satisfactory curative effect.

Objective:To evaluate the value of whole exome sequencing (WES) in prenatal clinical application.Methods:A total of 1 152 cases of congenital abnormal [including structural malformation, nuchal translucency (NT) thickening and intrauterine growth restriction] with traditional prenatal diagnosis [including G-band karyotype analysis and chromosome microarray analysis (CMA)] negative were analyzed. The congenital abnormal fetuses were divided into retrospective group and prospective group according to the time of WES detection, that is whether the pregnancy termination or not. According to the specific location of fetal malformation and their family history, the cohort was divided into subgroups. The clinical prognosis of all fetuses were followed up, and the effect of WES test results on pregnancy decision-making and clinical intervention were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in the third trimester or after birth were re-analyzed.Results:Among 1 152 families who received WES, 5 families were excluded because of nonbiological parents. Among the remaining 1 147 families, 152 fetuses obtained positive diagnosis (13.3%,152/1 147), including 74 fetuses in the retrospective group (16.1%,74/460) and 78 fetuses in the prospective group (11.4%,78/687). In fetuses with negative CMA and G-band karyotype analysis results but new phenotypes in the third trimester or after birth, the positive rate by WES data re-analysis was 4.9% (8/163). A total of 34 (21.3%, 34/160) fetuses were directly affected by the corresponding positive molecular diagnosis. Among 68 cases of live births with diagnostic variation grade 4, 29 cases (42.7%, 29/68) received appropriate medical intervention through rapid review of WES results.Conclusions:WES could increase the detection rate of abnormal fetuses with negative G-banding karyotype analysis and CMA by 13.3%. Prenatal WES could guide pregnancy decision-making and early clinical intervention. It might be an effective strategy to pay attention to the special follow-up of the third trimester and postnatal fetus and to re-analyze the WES data.