With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

OBJECTIVE: To investigate the load distribution on the more painful and less painful limbs in patients with mild-to-moderate and severe bilateral knee osteoarthritis (KOA) and explore the compensatory mechanisms in both limbs among bilateral KOA patients with different severity levels. METHODS: A total of 113 participants were enrolled between July 2022 and September 2023. This cohort comprised 43 patients with mild-to-moderate bilateral KOA (Kellgren-Lawrence grade 2-3), 43 patients with severe bilateral KOA (Kellgren-Lawrence grade 4), and 27 healthy volunteers (healthy control group). The visual analogue scale (VAS) score for pain, the Hospital for Special Surgery (HSS) score, passive knee range of motion (ROM), and hip-knee-ankle angle (HKA) were used to assess walking pain intensity, joint function, and lower limb alignment in KOA patients, respectively. Motion trajectories of reflective markers and ground reaction force data during walking were captured using a gait analysis system. Musculoskeletal modeling was then employed to calculate biomechanical parameters, including the peak knee adduction moment (KAM), KAM impulse, peak joint contact force (JCF), and peak medial/lateral contact forces (MCF/LCF). Statistical analyses were performed to compare differences in clinical and gait parameters between bilateral limbs. Additionally, one-dimensional statistical parametric mapping was utilized to analyze temporal gait data. RESULTS: Mild-to-moderate KOA patients showed the significantly higher HSS score (67.7±7.9) than severe KOA patients (51.9±8.9; t=8.747, P<0.001). The more painful limb in all KOA patients exhibited significantly greater HKA and higher VAS scores compared to the less painful limb ( P<0.05). While bilateral knee ROM did not differ significantly in mild-to-moderate KOA patients ( P>0.05), the severe KOA patients had significantly reduced ROM in the more painful limb versus the less painful limb ( P<0.05). Healthy controls showed no significant bilateral difference in any biomechanical parameters ( P>0.05). All KOA patients demonstrated longer stance time on the less painful limb ( P<0.05). Critically, severe KOA patients exhibited significantly higher peak KAM, KAM impulse, and peak MCF in the more painful limb ( P<0.05), while mild-to-moderate KOA patients showed the opposite pattern with lower peak KAM and KAM impulse in the more painful limb ( P<0.05) and a similar trend for peak MCF. CONCLUSION Patients with mild-to-moderate KOA effectively reduce load on the more painful limb through compensatory mechanisms in the less painful limb. Conversely, severe bilateral varus deformities in advanced KOA patients nullify compensatory capacity in the less painful limb, paradoxically increasing load on the more painful limb. This dichotomy necessitates personalized management strategies tailored to disease severity.
Humans ; Osteoarthritis, Knee/physiopathology* ; Range of Motion, Articular ; Male ; Female ; Middle Aged ; Biomechanical Phenomena ; Knee Joint/physiopathology* ; Pain Measurement ; Severity of Illness Index ; Aged ; Gait/physiology* ; Walking/physiology* ; Case-Control Studies ; Adult ; Weight-Bearing

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Objective:To discuss the regulatory effect of physiological tensile stress on the differentiation of chondrocytes,and to clarify the associated signaling pathway mechanism.Methods:The ATDC5 chondrocytes were cultured in vitro and subjected to physiological tensile stress by four-point bending cell mechanical loading device.Initially,the cells were divided into control group and tensile stress group(2 000 μstrain/2 h group),and further divided into different stress magnitudes(1 000,2 000,and 3 000 μstrain)for 2 h,and 2 000 μstrain for different duration time(1,2,and 4 h)groups;the cells without tensile stress were used as control group.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of type Ⅱ collagen(Col-Ⅱ),type Ⅹ collagen(Col-Ⅹ),aggregated proteoglycom(Aggrecan),sex-determining region Y-box protein 9(SOX9),vascular endothelial growth factor(VEGF),proliferating cell nuclear antigen(PCNA),Nel-like molecule tyep 1(Nell-1),Runt-related transcription factor 2(Runx2),Indian hedgehog(Ihh),patched homolog 1(Ptch-1),GLI family zinc finger protein 1(Gli-1),and hedgehog interacting protein 1(Hhip-1)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1,Runx2,and Ihh proteins in the cells in various groups.The ATDC5 cells were divided into control group,cyclopamine group,tensile stress group,and cyclopamine + tensile stress group.RT-qPCR method was used to detect the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of Nell-1 and Ihh proteins in the cells in various groups.Results:Compared with control group,the expression levels of Col-Ⅱ,Col-Ⅹ,Aggrecan,SOX9,VEGF,and PCNA mRNA in the cells in 2 000 μstrain/2 h group were significantly increased(P<0.01);after treated with 2 000 μstrain tensile stress for different duration time(1,2,and 4 h)or different tensile stresses(1 000,2 000,and 3 000 μstrain)for 2 h,compared with control group,the expression levels of Runx2 mRNA in the cells in other groups were increased with the prolongation of time or the increasing of tensile stress(P<0.01),and the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA were gradually increased(P<0.01),the expression levels reached the peaking at 2 000 μstrain/2 h,and then decreased but remained significantly higher than that in control group(P<0.01).The Western blotting results showed that the expression levels of Nell-1,Runx2,and Ihh proteins in the cells were consistent with the change trend of mRNA expression levels.After pre-treated with cyclopamine,compared with control group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine group were significantly decreased(P<0.01),and the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in tensile stress and cyclopamine+tensile stress groups were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1,Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine+tensile stress group were significantly increased(P<0.01);compared with tensile stress group,the expression levels of Ihh,Ptch-1,Gli-1,and Hhip-1 mRNA in the cells in cyclopamine + tensile stress group were significantly decreased(P<0.01).Compared with control group,the expression level of Ihh protein in the cells in cyclopamine group was significantly decreased(P<0.01),but there was no significant difference in expression level of Nell-1 protein in the cells between control group and cyclopamine group(P>0.05),while the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with cyclopamine group,the expression levels of Nell-1 and Ihh proteins in the cells in tensile stress group and cyclopamine + tensile stress group were significantly increased(P<0.01);compared with tensile stress group,in the expression levels of Nell-1 and Ihh proteins in the cells in cyclopamine + tensile stress group had no significant differences(P>0.05).Conclusion:After stimulated with physiological tensile stress,Nell-1 can activate the Ihh signaling pathway upstream,and regulate the differentiation of the ATDC5 chondrocytes.

Objective:To explore brain network properties and their relationship with cognitive function in children with spastic cerebral palsy (SCP) using diffusion tensor imaging (DTI) based graph theory analysis.Methods:The study was a cross-sectional study. Clinical and imaging data of 21 children with SCP (SCP group) and 32 healthy children (control group) who underwent cranial MRI at the Affiliated Hospital of Zunyi Medical University from August 2020 to April 2022 were analyzed retrospectively. 3D-T 1WI, DTI and Wechsler Intelligence Scale were assessed for all subjects. The Wechsler Intelligence Scale included the verbal comprehension index (VCI), the processing speed index (PSI), the work memory index (WMI), and the perceptual reasoning index (PRI), etc., and ultimately the full scale intelligence quotient (FSIQ) scores were obtained based on the indices of each subscale. Independent samples t-test was used to analyze the differences in the small world attributes [small-world index (σ), normalized shortest path length (λ), normalized clustering coefficients (γ)], global attributes [global efficiency (Eglob), local efficiency (Eloc), characteristic path length (Lp), clustering efficiency (Cp)] and node attributes [degree centrality(DC), nodal efficiency (Ne), betweeness centrality (Bc), nodal shortest path length (NLp), nodal clustering efficiency, nodal local efficiency] between two groups of children′s brain networks. Brain network indicators with statistically significant differences between the 2 groups were correlated with Wechsler Intelligence Scale scores using Spearman. Results:The FSIQ scores on the Wechsler Intelligence Scale and the VCI, WMI, PSI, and PRI were lower in the SCP group than in the control group, and the differences were all statistically significant (all P<0.05). Both groups of children′s brain networks had small world properties. Compared with the control group, Eglob decreased, Lp and λ increased in the SCP group (all P<0.05). Compared with the control group, DC and Ne in multiple brain regions decreased, NLp increased in the SCP group (all P<0.05, FDR corrected). Correlation analysis showed that DC in the right parsopercularis was positively correlated with FSIQ, VCI, WMI and PRI( r=0.53, 0.47, 0.47, 0.60, P=0.019, 0.045, 0.044, 0.020, respectively); NLp in the right parsopercularis was negatively correlated with PRI( r=-0.56, P=0.030); Ne in left paracentral, the right parsopercularis, right precentral, right postcentra were positively correlated with PRI( r=0.62, 0.56, 0.53, 0.54, P=0.015, 0.031, 0.044, 0.039, respectively); Ne in the right precentral was positively correlated with WMI ( r=0.48, P=0.039) in the SCP group. Conclusions:There are changes in the topological attributes of global and multiple regional brain networks in SCP. The changes in the attributes of nodes in the right parsopercularis, right precentral, right postcentral, and left paracentral could reflect cognitive dysfunction in children with SCP.

Objective Corruption is the most common cadaver phenomenon in forensic practice and an important basis for inferring time of death(PMI),but the definition of corruption degree and the construction of model inference models have always been difficult in the practice of forensic science.Methods In this study,the late postmortem phenomena were observed.Meanwhile,the microbial flora structure of gut and gravesoil and the nature of gravesoil were detected,for analyzing the changes before and after the key moment of abdominal rupture which naturally happened during the cadaver decay.Results The results found that from the macroscopic and microscopic levels,there were significant differences in cadaver decay,including microbial flora structure and gravesoil properties before and after the key moment of the natural abdominal rupture during cadaver decay.The phenomena are highly observable and can be accurately judged by forensic examinations,as well as related means in the field of biology and physiochemistry.In this study,this critical event was called Rupture Point.Conclusion The Rupture Point can be used as an important node for the assessment of cadaver decay degree in the practice of forensic medicine.It can be utilized for a cut-off point as well when constructing PMI inference models based on microbial flora structure changes.The accuracy of PMI inference models can be improved when the models were constructed in segments.

In the case of extremely shortage of donor kidney sources, the number of Expanded Criteria Donors (ECD) with relatively poor kidney quality and transplantation effect is increasing. In order to alleviate the contradiction between supply and demand by using transplantable kidneys as much as possible and avoid the failure or poor effect of transplantation caused by poor quality kidneys, the quality assessment and evaluation criteria of ECD kidney have become a research hotspot in the field of kidney transplantation. This paper analyzed the possible ethical defects in the research process, and put forward some suggestions for the transplantation team to strictly follow the ethical principles of "no harm", "beneficial" and "informed consent", and the organ transplantation ethics committee to pay attention to the ethical review of the quality evaluation process of ECD donor kidney.

Background::The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis.Method::The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors— Gata4, Foxa3, and Hnf1a—or alternatively, the expression of two transcription factors, Gata4 and Foxa3. In vivo, we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibrotic Col1a1-Cre ER; Cas9 fl/fl mice, effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination. Results::Activation of only two factors, Gata4 and Foxa3, via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes, such as drug metabolism and glycogen storage. Additionally, AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis. After 8 weeks of induction, the reprogrammed hepatocytes comprised 0.87% of the total hepatocyte population in the mice, significantly reducing liver fibrosis. Conclusion::CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases.

ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine（TCM） through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects， they were divided into the "1-2 seven" group （under 21 years old）， "3 seven" group （21-27 years old）， "4 seven" group （28-34 years old）， "5 seven" group （35-41 years old）， "6 seven" group （42-48 years old） and "7 seven" and older group （49 years old and above）. The age， average menstrual cycle in the past 3 months， basic hormone levels including follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， testosterone （T） and FSH/LH value， and anti-müllerian hormone （AMH） levels were collected and compared. ResultsA total of 1221 cases were included. The differences in FSH， LH， FSH/LH values， E₂， T， AMH levels and average menstrual cycle among the groups were statistically significant （P＜0.05 or P＜0.01）. AMH peaked in the "3 seven" group. Compared to those in the "3 seven" group， the FSH/LH value in the "4 seven" group increased， while the LH， AMH and T levels decreased， and the menstrual cycle was shortened （P＜0.01）. The FSH/LH， LH， AMH， T and menstrual cycle in the "5 seven" group were consistent with the changing trend of those in the "4 seven" group， while the FSH and E₂ levels in the "5 seven" group were significantly higher （P＜0.05 or P＜0.01）. Compared to those in the "5 seven" group， the FSH， LH and E₂ levels of the "6 seven" group increased， and the AMH and T levels continued to decrease （P＜0.05 or P＜0.01）. Compared to those in the "6 seven" group， the FSH and LH levels of the "7 seven" and older group continued to increase， and the AMH and E₂ levels decreased （P＜0.01）. ConclusionThe law of women reproductive aging in the "seven-year period" theory is basically consistent with the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. The reproductive capacity reaches its peak in the "three-seven-year period" and gradually moves towards reproductive aging in the "four-seven-year period".