ObjectiveTo investigate the influence of entecavir （ETV） versus tenofovir alafenamide fumarate （TAF） on renal function in previously untreated patients with chronic hepatitis B （CHB）. MethodsA retrospective analysis was performed for the clinical data of 167 previously untreated CHB patients who received ETV or TAF treatment for at least 48 weeks at the outpatient service of Department of Infectious Diseases in The First Affiliated Hospital of Nanchang University from September 2019 to November 2023， and according to the antiviral drug used， they were divided into ETV group with 117 patients and TAF group with 50 patients. In order to balance baseline clinical data， propensity score matching （PSM） was used for matching and analysis at a ratio of 2∶1， and the two groups were compared in terms of estimated glomerular filtration rate （eGFR） and the incidence rate of abnormal renal function at week 48. According to eGFR at week 48， the patients were divided into normal renal function group and abnormal renal function group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The multivariate Logistic regression analysis was used to investigate the influencing factors for abnormal renal function， and the receiver operating characteristic （ROC） curve was used to assess the performance of each indicator in predicting abnormal renal function. The Kaplan-Meier method was used to analyze the cumulative incidence rate of abnormal renal function， and the log-rank test was used for comparison. The analysis of variance with repeated measures was used to compare the dynamic changes of eGFR during antiviral therapy in CHB patients. ResultsAfter PSM matching， there were 100 patients in the ETV group and 50 patients in the TAF group. There were no significant differences in baseline clinical data between the ETV group and the TAF group （all P>0.05）， with an eGFR level of 112.29±9.92 mL/min/1.73 m² in the ETV group and 114.72±12.15 mL/min/1.73 m² in the TAF group. There was a reduction in eGFR from baseline to week 48 in both groups， and compared with the TAF group at week 48， the ETV group had a significantly lower eGFR （106.42±14.12 mL/min/1.73 m² vs 112.25±13.44 mL/min/1.73 m²， t=-2.422， P=0.017） and a significantly higher incidence rate of abnormal renal function （17.00% vs 4.00%， χ²=5.092， P=0.024）. After the patients were divided into normal renal function group with 131 patients and abnormal renal function group with 19 patients， the univariate analysis showed that there were significant differences between the two groups in age （Z=-2.039， P=0.041）， treatment drug （ETV/TAF） （χ²=5.092， P=0.024）， and baseline eGFR level （t=4.023， P<0.001）， and the multivariate Logistic regression analysis showed that baseline eGFR （odds ratio ［OR］=0.896， 95% confidence interval ［CI］： 0.841 — 0.955， P<0.001） and treatment drug （OR=5.589， 95%CI： 1.136 — 27.492， P=0.034） were independent influencing factors for abnormal renal function. Baseline eGFR had an area under the ROC curve of 0.781 in predicting abnormal renal function in CHB patients， with a cut-off value of 105.24 mL/min/1.73 m²， a sensitivity of 73.68%， and a specificity of 82.44%. The Kaplan-Meier curve analysis showed that the patients with baseline eGFR≤105.24 mL/min/1.73 m² had a significantly higher cumulative incidence rate of abnormal renal function than those with baseline eGFR>105.24 mL/min/1.73 m² （χ²=22.330， P<0.001）， and the ETV group had a significantly higher cumulative incidence rate of abnormal renal function than the TAF group （χ²=4.961， P=0.026）. With the initiation of antiviral therapy， both the ETV group and the TAF group had a significant reduction in eGFR （F=5.259， P<0.001）， but the ETV group only had a significant lower level of eGFR than the TAF group at week 48 （t=-2.422， P=0.017）； both the baseline eGFR≤105.24 mL/min/1.73 m² group and the baseline eGFR>105.24 mL/min/1.73 m² group had a significant reduction in eGFR （F=5.712， P<0.001）， and there was a significant difference in eGFR between the two groups at baseline and weeks 12， 24， 36， and 48 （t=-13.927， -9.780， -8.835， -9.489， and -8.953， all P<0.001）. ConclusionFor CHB patients initially treated with ETV or TAF， ETV antiviral therapy has a higher risk of renal injury than TAF therapy at week 48.

BACKGROUND: Several randomized controlled studies have suggested that the prophylactic use of proton pump inhibitors (PPIs) in intensive care unit (ICU) patients could not reduce the incidence of gastrointestinal bleeding (GIB) and may increase adverse events such as intestinal infection and pneumonia. Gut microbiota may play a critical role in the process. PPIs have been widely prescribed for GIB prophylaxis in patients with acute coronary syndrome (ACS). This study aimed to determine the short-term effects of PPI and histamine-2 receptor antagonist (H2RA) treatment on gut microbiota of ACS patients. METHODS: The study was designed as a single-blind, multicenter, three-parallel-arm, randomized controlled trial conducted at three centers in Beijing, China. We enrolled ACS patients at low-to-medium risk of GIB and randomized (2:2:1) them to either PPI ( n = 40), H2RA ( n = 31), or control group ( n = 21). The primary outcomes were the alterations in gut microbiota after 7 days of acid suppressant therapy. Stool samples were collected at baseline and 7 days and analyzed by 16S ribosomal RNA (rRNA) gene sequencing. RESULTS: There were no significant changes in the diversity of gut microbiota after the short-term use of acid suppressants, but the abundance of Fusobacterium significantly increased and that of Bifidobacterium significantly decreased, especially in PPI users. In addition, the abundance of some pathogenic bacteria, including Enterococcus and Desulfovibrio, was significantly elevated in the PPI users. The fecal microbiota of the PPI users included more arachidonic acid metabolism than that of control group. CONCLUSIONS: PPIs may increase the risk of infection by adversely altering gut microbiota and elevating arachidonic acid metabolism, which may produce multiple proinflammatory mediators. For ACS patients at low-to-medium risk of GIB, sufficient caution should be paid when acid-suppressant drugs are prescribed, especially PPIs. REGISTRATION www.chictr.org.cn (ChiCTR2000029552).
Humans ; Proton Pump Inhibitors/therapeutic use* ; Acute Coronary Syndrome/microbiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Male ; Middle Aged ; Histamine H2 Antagonists/therapeutic use* ; Aged ; Single-Blind Method

OBJECTIVE: To investigate of effectiveness of free fascia lata flap assisted by indocyanine green angiography (ICGA) in treatment of Myerson type Ⅱ and Ⅲ chronic Achilles tendon ruptures. METHODS: A clinical data of 14 patients with Myerson type Ⅱ and Ⅲ chronic Achilles tendon ruptures between March 2020 and June 2024 was retrospectively analyzed. All Achilles tendon defects were repaired with the free fascia lata assisted by ICGA during operation. There were 12 males and 2 females with an average age of 45.4 years (range, 26-71 years). The causes of Achilles tendon rupture included sports injury in 10 cases, Achilles tendon-related tendinopathy in 3 cases, and glass laceration injury in 1 case. The time from Achilles tendon rupture to operation was 4-40 weeks (median, 4.5 weeks). Preoperative MRI examination showed that the defect length of the Achilles tendon was 2-5 cm (mean, 3.2 cm). The operation time and intraoperative blood loss were recorded. The color Doppler ultrasound (CDU) and MRI were taken to observe the foot blood vessels and the tendon healing. The visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, Achilles Tendon rupture score (ATRS), and range of motion of the ankle joint were used to estimate the pain and function of ankle joint. RESULTS: All operations of the 14 patients were successfully completed. The operation time ranged from 3.00 to 4.50 hours (mean, 3.60 hours). The intraoperative blood loss ranged from 10 to 50 mL (mean, 36.4 mL). After operation, 1 patient had exudation at the recipient site, which healed after dressing change; the other incisions healed by first intention. All incisions at the donor sites healed by first intention. All patients were followed up 6-36 months (mean, 11.4 months). The CDU of the foot at 1 month after operation showed that the blood flow signal of the perforating vessels of the fascia lata flap was clear. The ankle MRI at 2 months after operation showed the good continuity of the Achilles tendon. No complication such as the Achilles tendon re-rupture, ankle stiffness, or scar contracture occurred during follow-up. Compared with preoperative score, the AOFAS score, ATRS score, and plantar flexion range of motion significantly increased at 1, 3, and 6 months after operation ( P<0.05), while the VAS score and dorsiflexion range of motion significantly decreased ( P<0.05). The AOFAS score, ATRS score, and VAS score at 3 and 6 months further improved when compared with those at 1 month ( P<0.05); however, there was no significant difference in the range of motion of the ankle joint ( P>0.05). There was no significant difference in above indicators between 3 and 6 months after operation ( P>0.05). CONCLUSION The treatment of Myerson type Ⅱ and Ⅲ chronic Achilles tendon ruptures with free fascia lata flaps under the guidance of ICGA has the advantages of precise design, fast healing, and a wide range of adaptability.
Humans ; Achilles Tendon/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Indocyanine Green ; Rupture/surgery* ; Aged ; Fascia Lata/transplantation* ; Angiography/methods* ; Free Tissue Flaps/blood supply* ; Plastic Surgery Procedures/methods* ; Tendon Injuries/diagnostic imaging* ; Treatment Outcome ; Chronic Disease

OBJECITVE: To investigate the effectiveness of three-dimensional (3D) printing-assisted vascularized fibular graft for repairing metatarsal defects. METHODS: Between November 2021 and February 2024, 11 patients with varying degrees of metatarsal defects caused by trauma were treated. There were 10 males and 1 female, aged 22-67 years, with a mean age of 51.2 years. The defect locations were as follows: the first metatarsal in 4 cases, the fifth metatarsal in 2 cases, the first and the second metatarsals in 1 case, the first to third metatarsals in 1 case, the third and the fourth metatarsals in 1 case, the third to fifth metatarsals in 1 case, and the first to fifth metatarsals in 1 case. The preoperative American Orthopaedic Foot & Ankle Society (AOFAS) score was 67.0 (48.5, 72.5). Based on 3D-printed bilateral feet models and mirrored healthy-side foot arch angles for preoperative planning and design, the vascularized fibular graft was performed to repair the metatarsal defects. At last follow-up, the medial and lateral longitudinal arches of bilateral feet were measured on weight-bearing X-ray films, and functional assessment was conducted using the AOFAS score. RESULTS: All operations were successfully completed, with an operation time ranging from 180 to 465 minutes (mean, 246.8 minutes). All incisions healed by first intention, with no occurrence of osteomyelitis. All patients were followed up 6-22 months (mean, 10 months). X-ray film reviews showed bone graft healing in all cases, with a healing time of 3-6 months (mean, 5 months). All patients underwent internal fixator removal at 6-12 months after operation. At last follow-up, no significant difference was observed in the medial and lateral longitudinal arches between the healthy and affected feet ( P>0.05). The AOFAS score of the affected foot was 78.0 (73.5, 84.0), showing a significant improvement compared to the preoperative score ( P<0.05). The effectiveness was rated as excellent in 1 case, good in 7 cases, fair in 2 cases, and poor in 1 case. Linear scarring remained at the donor site, with no functional impairment in adjacent joint movement. CONCLUSION 3D printing-assisted vascularized fibular graft for repairing metatarsal defects can effectively restore the physiological angle of the foot arch, facilitate the recovery of weight-bearing alignment, promote good bone healing, and yield satisfactory clinical outcomes.
Humans ; Printing, Three-Dimensional ; Middle Aged ; Male ; Fibula/blood supply* ; Female ; Metatarsal Bones/injuries* ; Adult ; Bone Transplantation/methods* ; Aged ; Plastic Surgery Procedures/methods* ; Young Adult ; Treatment Outcome

G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation-mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both in vitro and in vivo by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2-TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-κB activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Objective:To understand the current status of personal protection in occupational population at high risk for brucellosis in China and provide evidence for the evaluation of implementation of National Brucellosis Prevention and Control Plan (2016-2020).Methods:Four counties in Shanxi Province and Xinjiang Uygur Autonomous Region were selected to conduct a questionnaire survey in occupational population at high risk for brucellosis from December 2019 to July 2020 by using cross-sectional survey methods.Results:A total of 2 384 persons at high risk for brucellosis were surveyed, and the standardized utilization rate of personal protective equipment (PPE) was 20.13% (480/2 384). The utilization rate of glove, mask, rubber shoe, and work cloth were 38.26% (912/2 384), 31.80% (758/2 384), 32.01% (763/2 384) and 30.87% (736/2 384),respectively. There were significant differences in the utilization rate and standardized utilization rate of the four types of PPE among populations in different age, occupation, educational level and area groups (all P<0.001). The utilization rate and standardized utilization rate of PPE were lower in people over 60 years old, women, farmers, and those with lower educational level. The results of multivariate analysis showed that occupation and area were the influencing factors for the standardized utilization of PPE, the standardized utilization rates of PPE were higher in herdsmen and veterinarians. The standardized utilization rate of PPE in Yanggao County and Huocheng County was significantly higher than that in Zuoyun County and Hunyuan County. Conclusions:The utilization rate of the four types of PPE in occupational population at high risk for brucellosis was not high in China, and the standardized utilization rate was low, lower than the requirement in National Brucellosis Prevention and Control Plan, and there were significant differences among different areas. It is urgent to distribute PPE to occupational population at high risk for brucellosis and carry out health education about PPE utilization. Meanwhile, it is necessary to strengthen information exchange or sharing among different areas.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective To analyze the correlation of interferon-induced protein with tetratricopeptide repeats 1(IFIT1)with immune infiltration and prognosis of ovarian cancer(OC).Methods GEO database was employed to select the tumor immune related genes,and Kaplan-Meier and Prognoscan databases were used to identify the genes significantly associated with OC prognosis.The differential expression of IFIT1 between OC tissue and normal tissue were confirmed with GEPIA,Human Protein Atlas,and Timer databases.The expression level of IFIT1 in OC tissues with different grades and stages were analyzed in the UALCAN database.In addition,based on David database,GO enrichment analysis was used to analyze the interacting genes and proteins of IFIT1 in the String and Genemania databases.Timer and Tisidb databases verified the correlation between IFIT1 and immune cells mutually.Finally,after IFIT1 knockdown xenograft model was constructed based on lentiviral vector of IFIT1 shRNA,the tumor growth was observed in the transplanted nude mice,and infiltration of neutrophils was observed with immunohistochemical assay.Results FIT1,a tumor immune gene,selected from the GEO database,Kaplan-Meier and Prognoscan databases,was negatively correlated with the OC prognosis.GEPIA,Human Protein Atlas,Timer database,and UALCAN database indicated that the expression level of IFIT1 was significantly higher in the OC tissues than the normal ovarian tissues,and had no obvious correlation with tumor stage and grade.Analysis in String,Genemania,and David database found the interaction genes and proteins of IFIT1 were enriched in activation of 2'-5'oligonucleotide synthase,virus defense,and innate immunity,and other processes.The Timer database presented that IFIT1 was positively correlated with the infiltration of CD8+T cells,B cells,dendritic cells,neutrophils,and macrophage in OC,with neutrophils having the most significant correlation.Tisidb and GSCA also confirmed the positive correlation between IFIT1 and neutrophil infiltration in OC(P＜0.05).RT-qPCR and Western blotting confirmed that IFIT1 knockdown resulted in suppressed tumor growth in OC cells xenograft nude mice(P＜0.05)and reduced neutrophil infiltration in the xenograft tissues.Conclusion IFIT1 may influence the malignant progression of OC by promoting neutrophil infiltration.