Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective To investigate the epidemiological characteristics and spatial distribution characteristics of Clonorchis sinensis human infections in Guangdong Province from 2016 to 2022, so as to provide insights into formulation of the clonorchiasis control measures in the province. Methods Xinhui District of Jiangmen City, Longmen County of Huizhou City and Wengyuan County of Shaoguan City in Guangdong Province were selected as fixed surveillance sites for human clonorchiasis from 2016 to 2022, and additional 10% to 15% counties (districts) endemic for clonorchiasis were sampled from Guangdong Province as mobile surveillance sites each year from 2016 to 2022. A village (community) was randomly selected from each surveillance site according to the geographical orientations of east, west, south, north and middle, and subjects were randomly sampled from each village (community). C. sinensis eggs were detected in subjects’ stool samples using the Kato-Katz technique, and the prevalence and intensity of C. sinensis infections were calculated. In addition, subjects’ gender, age, ethnicity, educational level and occupation were collected. The Guangdong Provincial 1:1 million electronic map in vector format was downloaded from the National Geomatics Center of China, and kernel density analysis and spatial autocorrelation analysis of C. sinensis human infections in Guangdong Province from 2016 to 2022 were performed using the software ArcGIS 10.7. Results A total of 153 188 residents were tested for C. sinensis infections in Guangdong Province from 2016 to 2022, including 75 596 men (49.35%) and 77 592 women (50.65%), and there were 5 369 residents infected with C. sinensis, with 3.50% overall prevalence of infections. The prevalence rates of severe, moderate and mild C. sinensis infections were 0.76%, 7.26% and 91.97% among C. sinensis-infected residents in Guangdong Province from 2016 to 2022, and there were age-, gender-, ethnicity-, occupation- and educational level-specific prevalence of C. sinensis human infections (χ² = 2 578.31, 637.33, 52.22, 2 893.28 and 1 139.33, all P values < 0.05). Global spatial autocorrelation analysis showed a cluster in the prevalence of C. sinensis human infections in Guangdong Province (Moran’s I = 0.63, Z = 27.31, P < 0.05). Kernel density analysis showed that the prevalence of C. sinensis human infections with a high kernel density in Guangdong Province was mainly distributed along the Zhujiang River basin in Pearl River Delta areas, followed by in eastern and northern Guangdong Province. In addition, local spatial autocorrelation analysis identified 73 high-high clusters of the prevalence of C. sinensis human infections in Guangdong Province. Conclusions The prevalence of C. sinensis human infections was high in Guangdong Province from 2016 to 2022, and mild infection was predominant among all clonorchiasis cases, with spatial clusters identified in the prevalence of C. sinensis human infections. Targeted clonorchiasis control measures are required among high-risk populations and areas.

Objective To observe the value of right ventricle modified myocardial performance index(RV-Mod-MPI)for evaluating maternal obstetric antiphospholipid syndrome(OAPS)involving fetal right ventricular function.Methods Forty-five pregnant women with maternal OAPS(OAPS group)and 60 healthy pregnant women(control group)were prospectively enrolled.Fetal RV-Mod-MPI was obtained with tricuspid and pulmonary valve flow images by applying pulsed wave Doppler(PW).Late pregnancy conditions and data of newborns after delivery were recorded.The indexes were compared between groups.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was used to assess the efficacy of fetal RV-Mod-MPI for predicting adverse pregnancy outcomes in OAPS group.Results Compared with those in control group,OAPS group had higher fetal RV-Mod-MPI values,lower newborn birth weight and lower Apgar score at 1 min after birth,as well as higher probability of adverse pregnancy outcomes(all P＜0.05).The AUC of fetal RV-Mod-MPI for predicting adverse pregnancy outcome in OAPS group was 0.726.Conclusion RV-Mod-MPI could be used to evaluate maternal OAPS involving fetal right ventricular function and predict adverse pregnancy outcomes.

OBJECTIVE: To investigate the clinical application of high-frequency color Doppler ultrasound (HFCDU) in detecting perforators in the deep adipose layers for harvesting super-thin anterolateral thigh flap (ALTF). METHODS: Between August 2019 and January 2023, 45 patients (46 sides) with skin and soft tissue defects in the foot and ankle were treated, including 29 males and 16 females, aged from 22 to 62 years, with an average of 46.7 years. The body mass index ranged from 19.6 to 36.2 kg/m ², with an average of 23.62 kg/m ². The causes of injury included traffic accident injury in 15 cases, heavy object crush injury in 20 cases, mechanical injury in 8 cases, heat crush injury in 1 case, and chronic infection in 1 case. There were 20 cases on the left side, 24 cases on the right side, and 1 case on both sides. After thorough debridement, the wound size ranged from 5 cm×4 cm to 17 cm×11 cm. All patients underwent free super-thin ALTF transplantation repair. HFCDU was used to detect the location of the perforators piercing the deep and superficial fascia, as well as the direction and branches of the perforators within the deep adipose layers before operation. According to the preoperative HFCDU findings, the dimensions of the super-thin ALTF ranged from 6 cm×4 cm to 18 cm×12 cm. The donor sites of the flaps were directly sutured. RESULTS: A total of 55 perforators were detected by HFCDU before operation, but 1 was not found during operation. During operation, a total of 56 perforators were found, and 2 perforators were not detected by HFCDU. The positive predictive value of HFCDU for identifying perforator vessels was 98.2%, and the sensitivity was 96.4%. Among the 54 perforators accurately located by HFCDU, the orientation of the perforators in the deep adipose layers was confirmed during operation. There were 21 perforators (38.9%) traveled laterally and inferiorly, 12 (22.2%) traveled medially and inferiorly, 14 (25.9%) traveled laterally and superiorly, 5 (9.3%) traveled medially and superiorly, and 2 (3.7%) ran almost vertically to the body surface. Among the 54 perforators accurately located by HFCDU, 35 were identified as type 1 perforators and 12 as type 2 perforators (HFCDU misidentified 7 type 2 perforators as type 1 perforators). The sensitivity of HFCDU in identifying type 1 perforators was 100%, with a positive predictive value of 83.3%. For type 2 perforators, the sensitivity was 63.2%, and the positive predictive value was 100%. The surgeries were successfully completed. The super-thin ALTF had a thickness ranging from 2 to 6 mm, with an average of 3.56 mm. All super-thin ALTF survived, however, 1 flap experienced a venous crisis at 1 day after operation, but it survived after emergency exploration and re-anastomosis of the veins; 1 flap developed venous crisis at 3 days after operation but survived after bleeding with several small incisions; 3 flaps had necrosis at the distal edge of the epidermis, which healed after undergoing dressing changes. All 45 patients were followed up 6-18 months (mean, 13.6 months). Three flaps required secondary defatting procedures, while the rest had the appropriate thickness, and the overall appearance was satisfactory. CONCLUSION Preoperative application of HFCDU to detect the perforator in the deep adipose layers can improve the success and safety of the procedure by facilitating the harvest of super-thin ALTF.
Male ; Female ; Humans ; Thigh/surgery* ; Plastic Surgery Procedures ; Prospective Studies ; Skin Transplantation ; Free Tissue Flaps ; Burns ; Soft Tissue Injuries/surgery* ; Ultrasonography, Doppler, Color ; Crush Injuries/surgery* ; Perforator Flap ; Treatment Outcome

ObjectiveTo observe the intervention effect of Huaiqihuang granules （HQH） on immunoglobulin A vasculitis nephritis （IgAVN） mice and explore the underlying therapeutic mechanism. MethodFifty SPF-grade male Kunming mice were randomly divided into a normal group， an IgAVN model group， a dexamethasone group （2.5 mg·kg^-1·d^-1）， a low-dose HQH group （4 g·kg^-1·d^-1）， and a high-dose HQH group （8 g·kg^-1·d^-1）. The mouse model was established using oral administration of gliadin combined with intravenous injection of India ink. After successful modeling， the mice were euthanized after 4 weeks of gastric gavage according to groups. The 24 h urinary total protein （24 h UTP）， urine β₂-microglobulin （β₂-MG）， serum total protein， albumin， IgA， etc. were detected in each group. Flow cytometry was used to determine the proportion of T helper 17 （Th17） cells in spleen cell suspension. Western blot was employed to detect the expression of adenosine 5'-monophosphate-activated protein kinase α （AMPKα）， phosphorylated AMPKα （p-AMPKα）， acetyl-CoA carboxylase 1 （ACC1）， and phosphorylated ACC1 （p-ACC1） in Th17 cells. Pathological changes in the spleen and kidneys were observed. ResultCompared with the normal group， the IgAVN model group showed significant increases in 24 h UTP， urine β₂-MG， total cholesterol （P<0.05）， serum interleukin-17 （IL-17）， IgA， Th17 proportion in the spleen cell suspension， and IL-17 expression in the spleen tissue （P<0.01）， and significantly decreased serum total protein， albumin， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.01）. Compared with the IgAVN model group， in the 4th week， the 24 h UTP， urine β₂-MG， serum IL-17， IgA levels， and renal IgA deposition were significantly reduced in each treatment group （P<0.01）， and the Th17 proportion and IL-17 expression in spleen tissue were significantly decreased （P<0.05， P<0.01）. Serum albumin levels significantly increased （P<0.05）. Compared with the IgAVN model group， the dexamethasone group and the high-dose HQH group showed increases in serum total protein （P<0.01）， p-AMPKα/AMPKα， and p-ACC1/ACC1 expression of Th17 cells （P<0.05， P<0.01）. The high-dose HQH group showed a significant decrease in total cholesterol level （P<0.05）. Various treatment groups showed different degrees of improvement in spleen and kidney pathological changes. ConclusionHQH may affect Th17 cell differentiation by regulating the AMPK/ACC pathway， correcting immune inflammatory disorders， and exerting therapeutic effects on IgAVN.

Background Perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure may affect male reproductive health. There are regional differences in PFASs exposure levels among men of childbearing age in China, and current research results on associated influencing factors are inconsistent. Objective To investigate the levels of PFASs in serum and their determinants among men of childbearing age. Methods The participants (n=113, 22-45 years old) were from a cross-sectional study of exposure to environmental pollutants and male reproductive health damage in Hubei Province conducted from April to June 2013 at the Reproductive Medicine Center of Tongji Hospital, Wuhan, Hubei Province. Eleven kinds of PFASs were measured in serum by isotopic dilution-high performance liquid chromatography-tandem mass spectrometry. The included PFASs were prefluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), perfluorotridecanoic acid (PFTrDA), perfluorotetradecanoic acid (PFTeDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). Information about participants' demographic characteristics, lifestyle, and habits was collected by a set of self-designed questionnaires. The associations of demographic characteristics, lifestyle, and habits with exposure to PFASs were analyzed by linear regression. Results The major components of PFASs were PFOS and PFOA, and the concentrations expressed as M (P₂₅, P₇₅) were 8.31 (4.90, 17.79) ng·mL⁻¹ and 2.77 (2.18, 3.46) ng·mL⁻¹, respectively. The positive rates of six PFASs (PFOA, PFNA, PFDA, PFUdA, PFHxS, and PFOS) were 100%, followed by PFDoA and PFTrDA (87.61% and 88.59%, respectively). The linear regression results showed that age was positively associated with the levels of Σ₈PFASs (sum of the concentrations of the eight PFASs with a positive rate greater than 80%) (P < 0.05). The concentration of serum PFOA in men with monthly family income of 2000-4000 yuan was 53.73% (P < 0.01) higher than those in men with monthly family income of <2000 yuan. The serum concentrations of PFNA and PFTrDA were both 32.31% (P < 0.05) higher in men with monthly family income ≥4000 yuan than those in men with monthly family income <2000 yuan. The serum concentration of PFHxS in men who used plastic cups was 33.64% (P < 0.01) higher than that in men who did not report oral contact with plastic products (plastic tableware, plastic cups, and plastic bags for packing food). The serum concentrations of PFHxS, PFOS, and Σ₈PFASs were 33.64% (P < 0.01), 43.33% (P < 0.01), and 36.34% (P < 0.05) higher in men who bathed with laundry soap than those in men who did not use detergents. Men who bathed with toilet soap had a 34.99% (P < 0.05) higher serum concentration of PFHxS than those who bathed without detergents. Conclusion Men of childbearing age are exposed to PFASs extensively. Age, monthly household income, usage of laundry soap or toilet soap in bathing, and usage of plastic cups may influence the level of PFASs in serum. However, further investigation is needed to confirm these results.

Robotics ; Robotic Surgical Procedures ; Kidney Transplantation

Single-cell or low-input multi-omics techniques have revolutionized the study of pre-implantation embryo development.However,the single-cell or low-input proteomic research in this field is rela-tively underdeveloped because of the higher threshold of the starting material for mammalian embryo samples and the lack of hypersensitive proteome technology.In this study,a comprehensive solution of ultrasensitive proteome technology(CS-UPT)was developed for single-cell or low-input mouse oocyte/embryo samples.The deep coverage and high-throughput routes significantly reduced the starting material and were selected by investigators based on their demands.Using the deep coverage route,we provided the first large-scale snapshot of the very early stage of mouse maternal-to-zygotic transition,including almost 5,500 protein groups from 20 mouse oocytes or zygotes for each sample.Moreover,significant protein regulatory networks centered on transcription factors and kinases between the MII oocyte and 1-cell embryo provided rich insights into minor zygotic genome activation.

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness. METHODS: Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13⁺⁶ gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test. RESULTS: The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13⁺⁴ weeks (11⁺⁵ ~ 13⁺⁶ weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS. CONCLUSION NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.
Pregnancy ; Humans ; Female ; Adult ; Infant ; Nuchal Translucency Measurement/methods* ; Prenatal Diagnosis/methods* ; Chromosome Aberrations ; Aneuploidy ; Fetus/diagnostic imaging* ; Ultrasonography, Prenatal ; DNA Copy Number Variations ; Transcription Factors

The gut microbiome shows changes under a plateau environment, while the disbalance of intestinal microbiota plays an important role in the pathogenesis of irritable bowel syndrome (IBS); however, the relationship between the two remains unexplored. In this work, we followed up a healthy cohort for up to a year before and after living in a plateau environment and performed 16S ribosomal RNA (rRNA) sequencing analysis of their fecal samples. Through evaluating the participants' clinical symptoms, combined with an IBS questionnaire, we screened the IBS sub-population in our cohort. The sequencing results showed that a high-altitude environment could lead to changes in the diversity and composition of gut flora. In addition, we found that the longer the time volunteers spent in the plateau environment, the more similar their gut microbiota composition and abundance became compared to those before entering the plateau, and IBS symptoms were significantly alleviated. Therefore, we speculated that the plateau may be a special environment that induces IBS. The taxonomic units g_Alistipes, g_Oscillospira, and s_Ruminococcus_torques, which had been proved to play important roles in IBS pathogenesis, were also abundant in the IBS cohort at high altitudes. Overall, the disbalance of gut microbiota induced by the plateau environment contributed to the high frequency of IBS and the psychosocial abnormalities associated with IBS. Our results prompt further research to elucidate the relevant mechanism.