[Overexpression of ubiquitin-conjugating enzyme 2T induces radiotherapy resistance in hepatocellular carcinoma by enriching regulatory T cells in the tumor microenvironment].

OBJECTIVE: To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T (UBE2T) on radiosensitivity of hepatocellular carcinoma (HCC). METHODS: Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector, and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay. The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice, and tumor growth following irradiation were recorded. The xenografts were collected for analyzing infiltration of CD4+ T cells and regulatory T cells (Tregs) using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting. The correlations of UBE2T expression with immune cell infiltration, glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database, and the results were verified in a co-culture system of Hepa1-6 cells and Tregs. RESULTS: UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models (especially in C57BL/6 mice). CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells, T follicular helper cells, M2 macrophages, monocytes, lymphocytes and Tregs in HCC. The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA, and irradiation increased infiltration of CD4+ T cells and Tregs in the tumor microenvironment. Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration. GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC. In the cell co-culture system, UBE2T overexpression significantly enhanced lactate production, proliferation and immunosuppressive functions of Tregs. CONCLUSION: A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

[Transcription factor activator protein 2C contribute to molar development in mice].

Objective: Explore the expression pattern of transcription factor activator protein 2C (Tfap2c) and identify the roles of Tfap2c during tooth development. Methods: Real-time quantitative PCR (RT-qPCR) was used to analyze the relative expression level of Tfap2c in various organs of embryo day(E)14.5 mouse embryos and mouse molar germs at E12.5-E18.5 and postnatal day (P)0-P7. The expression position of Tfap2c in mouse molar germs was demonstrated by frozen section immunofluorescence staining. Cultured mandibular molar germs were transfected with control siRNA or Tfap2c siRNA to evaluate the effect of Tfap2c on tooth molar germs development, and RT-qPCR was used to detect the relative expression level of genes related to odontoblast expression. Dental mesenchymal cells were isolated from E14.5 molar germs and transfected with control siRNA or Tfap2c siRNA, cell counting kit 8 and scratch healing test were applied to detect dental mesenchymal cell viability and migration. Results: Tfap2c was highly expressed in the early development period of mouse molar germs. Tfap2c was expressed in the epithelial and mesenchymal tissues of E13.5 mouse molar germs and there was no significant difference of relative expression of Tfap2c between them (t=1.06, P=0.472). Tfap2c was expressed in mesenchymal tissues of E14.5 mouse molar germs and the relative expression of Tfap2c in mesenchymal tissues was significantly higher than epithelial tissues (t=37.29, P<0.0001). For molar germs transfected with Tfap2c siRNA, the relative height of cusps (0.708±0.171) and the ratio of cusp height and crown height (0.321±0.068) was significantly lower than control group (1.000±0.287 and 0.483±0.166) (t=2.79, P=0.012; t=2.85, P=0.015). But there was no significant difference in relative height (1.078±0.206, 0.993±0.254, t=0.83, P=0.419)and relative width (1.000±0.116, 0.999±0.122, t=0.01, P=0.992) of crowns between two groups. The relative expression level of genes related to odontoblast expression was decreased (Dspp: t=15.33, P<0.001; Dmp1: t=13.81, P<0.001). Tfap2c siRNA hinders cell migration in dental mesenchymal cells (t=29.86, P=0.001), but there was no significant difference in CCK8 absorbance value between two groups. The relative expression level of genes related to odontoblast expression was also decreased in dental mesenchymal cells transfected with Tfap2c siRNA (Dspp: t=3.86, P=0.031; Dmp1; t=4.36, P=0.022). Conclusions: Tfap2c highly expressed in the early morphogenesis period of mouse molar germs, mainly in mesenchymal tissues. Tfap2c affected the cusps formation of mouse molar germs and migration of dental mesenchymal cells.

[Characterizing immune microenvironment cell composition of chronic rhinosinusitis with nasal polyps based on mass cytometry technology].

Objective: To analyze the cellular composition characteristics of the nasal tissue immune microenvironment in patients with control, chronic rhinosinusitis without nasal polyps (CRSsNP), non-eosinophilic chronic rhinosinusitis with nasal polyps (neCRSwNP), and eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) using mass cytometry flow technology. Methods: Thirteen CRS patients who underwent endoscopic nasal surgery at the Department of Otorhinolaryngology Head and Neck Surgery of Peking Union Medical College Hospital from March to December 2022 were recruited, including 8 males and 5 females, aged 22.3 to 58.3 years. Three control mucosae were obtained from normal ethmoid or sphenoid sinuses of patients with benign tumors of the temporal fossa or non-functional pituitary adenomas who underwent endoscopic surgery, excluding allergic rhinitis and sinusitis. Sixteen clinical tissue samples (3 of control, 3 of CRSsNP, 4 of neCRSwNP, and 6 of eCRSwNP) were prepared into single-cell suspensions. Mass cytometry flow detection was performed using a combination of 42 molecular markers to analyze the differences in cell subpopulations among the groups. Data were analyzed using GraphPad Prism 9. Results: Based on the mass cytometry flow results, cells from control, CRSsNP, neCRSwNP, and eCRSwNP were divided into seven main cell subgroups, with detailed subgrouping of T/NK cells and myeloid cells. In T/NK cells, compared with the control group, the number of NK CD56bright cells increased in the CRSsNP group, while NK CD56dim cells decreased; compared with the CRSsNP group, the eCRSwNP group showed a decrease in NKT cells and CD4+Tem cells; compared with the CRSsNP group, the eCRSwNP group showed a significant increase in CD25 expression within Treg cells; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in Tbet expression in CD8+Teff cells and CD8+TRM cells; in eCRSwNP, the expression of CD103 in CD8+TRM cells was significantly lower than in CRSsNP. In myeloid cells, compared with the other three groups, the eCRSwNP group showed a significant increase in macrophages and a significant decrease in cDC1 and monocytes; compared with the control group and CRSsNP, the eCRSwNP group also showed a significant decrease in resting state macrophages; compared with the CRSsNP group, the eCRSwNP group showed a significant decrease in the level of CX3CR1 within cDC2 and monocytes; the expression levels of NLRP3 in cDC2 and macrophages in the eCRSwNP group were significantly higher than in the other three groups; compared with the control group, the expression levels of Gata3 in cDC2 and macrophages in the eCRSwNP group were also significantly increased; additionally, the expression of CCR2 within monocytes in the eCRSwNP group was lower than in the CRSsNP group. In ILC, compared with the control group, the expression of CCR6 decreased in the eCRSwNP group. Conclusions: Compared with the control group, CRSsNP, and neCRSwNP, eCRSwNP shows an increase in macrophage number, a decrease in cDC1 and resting state macrophages, and depletion of protective cells CD103+CD8+TRM. Additionally, the expression levels of CCR2 and CX3CR1 in monocytes of eCRSwNP are decreased.

[Association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40-89 in selected areas of China].

Objective: To investigate the association of urinary cadmium levels with peripheral leukocyte classification counts among middle-aged and older adults aged 40 to 89 years in selected areas of China. Methods: The research was based on the survey of the impact of soil quality of agricultural land on human health in typical areas conducted in 2019-2020. A total of 5 600 middle-aged and older adults aged 40 to 89 years were included by using a multi-stage stratified random sampling method. Baseline characteristics of the subjects were collected and physical examinations were performed. Random midstream urine was collected to measure urinary cadmium and urinary creatinine and fasting venous blood was collected to measure the leukocyte count, neutrophil count, lymphocyte count, monocyte count and eosinophil count. The linear mixed effect model was used to analyse the association of urinary cadmium levels with leukocyte classification counts, and the dose-response relationship between them was analyzed by using the restricted cubic spline (RCS) function. Results: The age of the subjects was (63.17±12.02) years; 2 851 (50.91%) were males; and the M (Q1, Q3) of urinary creatinine-corrected urinary cadmium levels was 2.69 (1.52, 4.69) µg/g·creatinine. After adjusting for confounding factors, the results of linear mixed effects model analysis showed that for each 1-unit increase in urinary creatinine-corrected urinary cadmium level, the percentage change [% (95%CI)] of leukocyte count and lymphocyte count was -1.70% (-2.61%, -0.79%) and -1.57% (-2.86%, -0.26%), respectively. RCS function showed a negative linear relationship between urinary creatinine-corrected urinary cadmium levels and leukocyte counts and lymphocyte counts, respectively (all Pnon-linear>0.05). Conclusion: Urinary cadmium levels are negatively associated with leukocyte count and lymphocyte count among middle-aged and older adults aged 40 to 89 years in selected areas of China.

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas.

AIMS: This study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). MATERIALS AND METHODS: The 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)-(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). RESULTS: Compared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27-4.12% and 0.64-2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. CONCLUSION: The functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Bromocriptine sensitivity in bromocriptine-induced drug-resistant prolactinomas is restored by inhibiting FGF19/FGFR4/PRL.

PURPOSE: At present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment. METHODS: In our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice. RESULTS: Consistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels. CONCLUSION: Overall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas.

Comprehensive evaluation of advanced platelet-rich fibrin in common complications following sagittal split ramus osteotomy: a double-blind, split-mouth, randomized clinical trial.

The sagittal split ramus osteotomy (SSRO) carries potential risks and complications. A double-blind, split-mouth, randomized clinical trial was performed, involving 30 patients undergoing mandibular setback. Advanced platelet-rich fibrin (A-PRF) was applied to one side, and the other side served as a control. The volume of postoperative drainage over 24 h was recorded. At 1, 2, and 5 days, and 3 months postsurgery, nerve recovery was assessed using the two-point discrimination test (TPD), while pain was evaluated using a visual analogue scale (VAS pain). Facial swelling was evaluated by taking linear measurements from facial reference points at the same time intervals. In the treatment group, the 24-hour drainage volume was lower (P = 0.011), pain was better on day 5 (P = 0.011), and TPD was better on day 2 (P = 0.011), day 5 (P = 0.007), and 3 months postoperatively (P = 0.020) than in the control group. There was also less facial swelling in the treatment group when compared to the baseline of 3 months postoperative (day 1, P = 0.012; day 2, P = 0.001; day 5, P = 0.011). The difference in bone mineral density (HU) at 3 months between the treatment group (469.7 ± 134.2) and the control group (348.3 ± 127.2) was statistically significant (P = 0.011), in favour of the treatment group. A-PRF may reduce postoperative complications such as neurosensory disturbance of the inferior alveolar nerve, pain, swelling, and drainage while enhancing bone healing in the osteotomy gap following SSRO. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Register (ChiCTR2200064534).

[Subphenotypes and precision medicine in acute respiratory distress syndrome].

The presence of significant complex heterogeneity among patients with acute respiratory distress syndrome (ARDS) is a major reason for the failure of drug treatments. Precision medicine seeks to elucidate the potential mechanisms of ARDS heterogeneity, define subtypes of ARDS patients with specific characteristics, and rapidly identify the patient groups most likely to benefit from targeted treatments, thereby maximizing treatment efficiency and minimizing adverse reactions. This review discusses on the current state of research on ARDS subtypes from multiple perspectives, including etiology, onset time, radiology, pathology, oxygenation index, respiratory mechanics, protein biomarkers, genetics, transcriptomics, and microbiomics, with the aim of deepening the understanding of the pathogenesis of ARDS and thereby guiding precision treatment of ARDS.

[Interpretation of the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030)].

On June 16, 2023, National Disease Control and Prevention Administration of the People's Republic of China, in collaboration with other ministries, formulated and issued the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023-2030). The implementation of this plan provides an important basis for achieving the targets set in the "Healthy China 2030" action plan and the implementation of the rural revitalization strategy. This paper describes the background, principles, targets, control strategies, safeguard measures and effectiveness evaluation of the plan, in order to guide the scientific and standardized implementation of actions for schistosomiasis elimination at the grassroots level, and facilitate the progress towards elimination of schistosomiasis in China with a high quality.

[Clinical significance of immune checkpoint inhibitors in neoadjuvant therapy for gastric cancer].

Multiple prospective clinical studies have demonstrated that chemotherapy combined with immune checkpoint inhibitors (ICIs) can prolong the survival of patients with far-advanced gastric cancer. For patients with locally advanced gastric cancer (LAGC), preoperative neoadjuvant chemotherapy combined with immunotherapy has also achieved some encouraging results which benefit some patients, achieve clinical downstage, attenuate hidden metastases, increase R0 resection rate and reduce postoperative recurrence rate, etc. How to apply ICIs or combine immunotherapy with other therapies correctly in the course of neoadjuvant comprehensive treatment for patients with LAGC is still a very challenging and difficult problem. There are three basic principles in immunotherapy to be grasped: (1) Based on high-level clinical practice guidelines; (2) Based on the results of high-quality evidence-based medical research; and (3) Based on molecular pathology and tumor biomarkers. Perioperative immunotherapy for gastric cancer can be correctly applied if these three principles are organically integrated. Referring to the results of domestic and international clinical research in recent years, the three basic principles are demonstrated in this article for readers.

[Call for attention to the value and challenge of liquid biopsy in diagnosis and treatment for peritoneal metastasis of gastric cancer].

Peritoneal metastasis is the common route of metastasis in gastric cancer and is a major cause of death in advanced gastric cancer. Early intervention with comprehensive treatment can effectively improve the prognosis of some patients with peritoneal metastasis. However, early peritoneal metastasis in gastric cancer is predominantly micro-metastasis, which cannot be effectively evaluated by imaging studies. Moreover, the detection of disseminated cancer cells in peritoneal lavage suffers from a low detection rate and significant heterogeneity. In recent years, the development and application of new liquid biopsy technologies such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have provided new means to assess potential peritoneal metastasis at the cellular and molecular levels, gradually becoming research hotspots in this field. This review will summarize the relevant progress of liquid biopsy in peritoneal metastasis, which holds significant importance for improving the prognosis of gastric cancer patients in China.

[Diagnostic value of whole blood cell parameters logistic regression model for radiation injury on radiation workers].

Objective: To explore the diagnostic value of whole blood cell parameters logistic regression model for radiation injury on radiation workers by comparing the differences of whole blood cell parameters between occupational radiation injury population and occupational health examination population. Methods: In February 2023, 184 radiation workers who received occupational health examinations in our hospital and occurrenced chromosome aberration from July 2021 to July 2022 were retrospectively selected as the radiation injury group. And other 184 radiation workers encountered in the same period without chromosome aberration occurrence were selected as the control group. Collected whole blood cell parameters from two groups of research subjects, conducted comparative analysis, constructed a logistic regression model, and evaluated the diagnostic value of the logistic regression model for radiation injury on radiation workers by receiver operating characteristic curve (ROC) and area under curve (AUC) . In addition, with the same standard, 60 radiation workers with chromosome aberration and 60 radiation workers without chromosome aberration from August 2022 to January 2023 were included in the validation queue to validate the logistic regression model. Results: Neu_X, Neu_Y, Neu_Z, Lym_X, Lym_Y, Lym_Z, Mon_X, Mon_Y, Mon_Z, Micro, MCHC in the radiation injury group were significantly higher than those in the control group, and the difference was statistically significant (P<0.05) . And MCV and Macro in the radiation injury group were lower than those in the control group, and the difference was statistically significant (P<0.05) . Moreover, logistic regression analysis showed that Lym_X, Lym_Y, Lym_Z, MCHC, Micro were all independent risk factors for diagnosing radiation injury on radiation workers (OR=1.08、1.02、0.99、1.06、51.32, P<0.05) . ROC curve analysis showed that the AUC, sensitivity, specificity, and accuracy of the logistic regression model based by Lym_X, Lym_Y, Lym_Z, MCHC and Micro in diagnosing radiation injury on radiation workers were 0.80, 85.9%, 65.8% and 75.9% respectively. The validation queue verified the logistic regression model and the AUC, sensitivity, specificity, and accuracy of the logistic regression model were 0.80, 81.7%, 71.7% and 76.7% respectively, the model fitted well. Conclusion: Radiation damage can cause changes in multiple whole blood cell parameters of radiation workers. The logistic regression model based by Lym_X, Lym_Y, Lym_Z, MCHC and Micro showed good diagnosis ability and can be used for the screening of radiation injury on radiation workers.

[Influence of paraspinal muscle degeneration and postoperative Roussouly classification restoration on mechanical complications in female patients with degenerative scoliosis after surgery].

Objective: To investigate the impact of lumbar paraspinal muscle degeneration and postoperative failure to restore ideal Roussouly classification on the occurrence of mechanical complications (MC) following long-segment spinal correction surgery in female patients with degenerative scoliosis (DS). Methods: The clinical data of 72 female DS patients who underwent long-segment spinal correction surgery in Gulou Hospital from June 2017 to November 2021 were retrospectively analyzed. According to whether restoring the ideal Roussouly classification after surgery, the patients were divided into R group(recovery group) (n=51) and N group(non-recovery group) (n=21). According to whether mechanical complications occurred after operation within two years, the patients were divided into MC (mechanical complications)group (n=24) and NMC(non-mechanical complications) group (n=48). The RM group (n=14) experienced mechanical complications in the R group, while the RN group (n=37) did not. The NM group (n=10) experienced mechanical complications in the N group, while the NN group (n=11) did not.Radiographic assessment included Sagittal parameters of spine and pelvis, standardized cross-sectional area (SCSA) and fat infiltration rate (FI%) of paraspinal muscle at each lumbar disc level. Results: The age of DS patients in this study was (61.4±6.2) years.The incidence of MC was 33.33%(n=24)in all patients. The incidence of MC was 27.45%(n=14)in group R and 47.62%(n=10) in group N. The correction amount of pelvic tilt angle (PT) (-11.62°±10.06° vs -7.04°±8.45°, P=0.046) and T1 pelvic angle(TPA)(-12.88°±11.23° vs -7.31°±9.55°, P=0.031)during surgery were significantly higher in MC group compared to the NMC group. In group R, the FI% of paraspinal muscles in each lumbar segment of patients with postoperative MC was higher than that in patients without MC (P<0.05). In the R and N groups, there was no significant difference inthe SCSA of the lumbar paravertebral muscles between patients with postoperative MC and those without MC at each level (all P>0.05). Multivariate logistic regression analysis showed that the average FI% of lumbar PSM was correlated with the occurrence of MC after spinal fusion in DS patients.The average FI% of lumbar PSM≥22.63% was a risk factors for MC after spinal fusion (P=0.010,OR=1.088, 95%CI:1.020-1.160). Conclusions: Female DS patients with higher degree of preoperative paraspinal muscle degeneration have a higher incidence of postoperative mechanical complications. For these patients,.there is still a higher risk of mechanical complications after surgery even if the ideal Roussouly classification is restored after surgery.

[Role of mitochondrial autophagy and the curative effect of rehmannia glutinosa leaves total glycoside capsules on nucleos(t)ide drug-induced renal injury].

Objective: To study the curative effect of rehmannia glutinosa leaves total glycoside capsules and the role of mitochondrial autophagy on nucleos(t)ide drug-induced renal injury. Methods: Adefovir dipivoxil (ADV) was used to construct a hepatitis B virus (HBV) transgenic mouse model for renal injury. Renal function was measured in each group at one and two weeks of modeling. Mitochondrial autophagy indicators were measured at two weeks of modeling in renal tissue. Transmission electron microscopy was used to detect mitochondrial autophagy phenomena in renal tissue. The model was established for two weeks. Mouse with renal injury were treated with rehmannia glutinosa leaves total glycoside capsules or isotonic saline for eight weeks by intragastric administration. Renal function was measured. Renal tissue morphology was observed. Mitochondrial autophagy indicators were detected in renal tissue. The protective effect of different concentrations of verbascoside (the main active ingredient of rehmannia glutinosa capsule) was observed on HK-2 cell damage induced by ADV. HK-2 cells were divided into control, ADV, and ADV plus verbascoside groups. The effects of verbascoside at different times and concentrations were observed on the HK-2 mitochondrial autophagy indicators. Fifty patients with chronic hepatitis B were collected who presented with renal injury after treatment with nucleos(t)ide analogs. The random number method was used to divide 29 cases into a control group that received conventional treatment. The treatment group of 21 cases was treated with rehmannia glutinosa leaves total glycoside capsules on the basis of the control group. Serum creatinine (Scr) and urinary protein were detected at eight weeks.The χ(2) test or t-test was used for statistical analysis. Results: Compared with the control group, two weeks of modeling in the ADV group induced renal function injury in HBV mice. The expression of autophagy indicators was higher in the renal tissue of the ADV group than that of the control group. Transmission electron microscopy had revealed mitochondrial autophagy in the renal tissue of the ADV group. Compared with the control group, the renal function of HBV mice treated with rehmannia glutinosa leaves total glycoside capsules improved for two months, and the expressions of autophagy indicators were down-regulated.Verbascoside promoted proliferation in ADV-damaged HK-2 cells, and the expression of autophagy indicators was down-regulated compared with the ADV alone group. In 50 patients with renal function injury, the urinary protein improvement was significantly superior in the treatment group than that in the control group, with eighteen and three cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with a statistically significant difference (χ(2) = 9.975 0, P = 0.001 6). Serum creatinine was decreased in the treatment group compared with the control group, with 11 and 10 cases being effective and ineffective in the treatment group and 12 and 17 cases being effective and ineffective in the control group, with no statistically significant difference (χ(2) = 0.593 5, P = 0.441 1). Conclusion: Rehmannia glutinosa leaves total glycoside capsule can improve the nucleos(t)ide drug-induced renal function injury in chronic hepatitis B, possibly playing a role via inhibiting PINK1/Parkin-mediated mitochondrial autophagy.

[Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns].

Objective: To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis. Methods: This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results: Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions: The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

[Epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023].

Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023. Methods: The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed. Results: A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M (Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant (P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age (P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion: Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

[RBMX overexpression inhibits proliferation, migration, invasion and glycolysis of human bladder cancer cells by downregulating PKM2].

OBJECTIVE: To investigate the role of RNA-binding motif protein X-linked (RBMX) in regulating the proliferation, migration, invasion and glycolysis in human bladder cancer cells. METHODS: A lentivirus vectors system and RNA interference technique were used to construct bladder cancer 1376 and UC-3 cell models with RBMX overexpression and knockdown, respectively, and successful cell modeling was verified using RT-qPCR and Western blotting. Proliferation and colony forming ability of the cells were evaluated using EdU assay and colony-forming assay, and cell migration and invasion abilities were determined using Transwell experiment. The expressions of glycolysis-related proteins M1 pyruvate kinase (PKM1) and M2 pyruvate kinase (PKM2) were detected using Western blotting. The effects of RBMX overexpression and knockdown on glycolysis in the bladder cancer cells were assessed using glucose and lactic acid detection kits. RESULTS: RT-qPCR and Western blotting confirmed successful construction of 1376 and UC-3 cell models with RBMX overexpression and knockdown. RBMX overexpression significantly inhibited the proliferation, clone formation, migration and invasion of bladder cancer cells, while RBMX knockdown produced the opposite effects. Western blotting results showed that RBMX overexpression increased the expression of PKM1 and decreased the expression of PKM2, while RBMX knockdown produced the opposite effects. Glucose consumption and lactate production levels were significantly lowered in the cells with RBMX overexpression (P < 0.05) but increased significantly following RBMX knockdown (P < 0.05). CONCLUSION: RBMX overexpression inhibits bladder cancer progression and lowers glycolysis level in bladder cancer cells by downregulating PKM2 expression, suggesting the potential of RBMX as a molecular target for diagnosis and treatment of bladder cancer.

[Clinical study of the Cobb+1 to Cobb fusion strategy for Lenke 5C adolescent idiopathic scoliosis patients with the lower lumbar apex].

Objective: To investigate the indications and surgical outcome of Cobb+1 to Cobb fusion strategy in Lenke 5C adolescent idiopathic scoliosis (AIS) patients with the lower lumbar apex. Methods: The clinical data of Lenke 5C AIS patients treated in Nanjing Drum Tower Hospital from August 2015 to December 2018 were retrospectively analyzed. The patients were followed-up for at least 2 years after surgery and treated with selective Cobb+1 to Cobb fusion strategy. The patients were divided into the normal lumbar apex group (apex location of the main curve was between T12 and L1) and the lower lumbar apex group (apex location of the main curve was below the disc of L1/L2). The occurrence of proximal decompensation in the two groups was compared. In addition, according to whether the patients had proximal decompensation at the last follow-up, the patients in the lower lumbar apex group were further divided into proximal decompensation group and non-decompensation group. The radiographic parameters and Scoliosis Research Society-22 (SRS-22) scores of the two groups were compared. Results: A total of 52 patients (19 cases in the normal lumbar apex group and 33 cases in the lower lumbar apex group), aged (15.3±1.6) years, were followed up for 2-5 (3.2±1.2) years. Six patients (6/19) in the normal lumbar apex group and 5 cases (15.2%) in the lower lumbar apex group showed proximal decompensation during follow-up, and the incidence was significantly higher in the normal lumbar apex group (P=0.034). Within the lower lumbar apex group, the patients with proximal decompensation (n=5) showed similar Risser grade, baseline thoracic Cobb angle, and main Cobb angle as those without proximal decompensation(n=28), and the differences were all not statistically significant (all P>0.05). However, the baseline thoracic/lumbar apical vertebra translation (AVT) ratio was significantly larger in patients with proximal decompensation (0.6±0.2 vs 0.4±0.2, P=0.042), but the postoperative upper instrumented vertebra (UIV) tilt angle was similar (4.5°±2.3° vs 6.2°±3.4°, P=0.312). Conclusion: Cobb+1 to Cobb fusion strategy, selecting UIV at 1 level above upper end vertebra (UEV), could be performed in Lenke 5C patients with the lower lumbar apex location. In addition, UIV could be selected at UEV+1 in patients with small baseline thoracic curve.