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.

Objective:To investigate the status of medical care seeking delay and diagnosis delay of pulmonary tuberculosis (PTB) patients in Tongzhou District and Changping District of Beijing, analyze the related factors and put forward suggestions for early detection and scientific management of PTB patients.Methods:A retrospective epidemiological survey was conducted to collect the incidence data of PTB registered in Tongzhou and Changping from January 1 to December 31, 2021 by using the Chinese Tuberculosis Information Management System, and telephone interview were used for information supplement. Multivariate logistic regression model and decision tree model were used to analyze the influencing factors of medical care seeking delay and diagnosis delay of PTB patients.Results:In 2021, the medical care seeking delay time M( Q1, Q3) in the PTB patients in Tongzhou and Changping was 11 (5, 26) days, with a delay rate of 41.71%. Results from multivariate logistic regression model analysis revealed that factors influencing the medical care seeking delay included regular health check-up ( OR=0.033, 95% CI: 0.008-0.147), coughing for less than 2 weeks or showing any symptom of PTB before medical care seeking ( OR=0.378, 95% CI: 0.215-0.665), showing other symptoms before medical care seeking( OR=2.791, 95% CI: 1.710-4.555), no work or school in medical care seeking ( OR=2.990, 95% CI: 1.419-6.298). The diagnosis delay time M( Q1, Q3) in the PTB patients was 8 (0, 18) days, with a delay rate of 35.20%. Multivariate logistic regression model analysis revealed that the factors influencing the diagnosis delay of PTB included being diagnosed at a specialized tuberculosis hospital ( OR=0.426, 95% CI: 0.236-0.767) or a tuberculosis prevention and control institution ( OR=1.843, 95% CI: 1.061-3.202) and being traced as a source of infection ( OR=2.632, 95% CI: 1.062-6.521). The overall performance of the multivariate logistic regression model was comparable to that of the decision tree model, with the decision tree model exhibiting higher sensitivity but lower specificity. Conclusions:The medical care seeking delay rate and diagnosis delay rate of tuberculosis in Tongzhou and Changping were at low levels in 2021. However, it is still necessary to strengthen the health education and active screening, improve the public awareness of PTB prevention and control, and further improve the level of medical services and medical access to reduce the medical care seeking delay and diagnosis delay of PTB patients.

Objective:To investigate the clinical efficacy of pentoxifylline sequential therapy combined with rasagiline and levodopa in the treatment of elderly patients with symptoms of Parkinson disease (PD), and the influence on hemorheology and serum Toll-like receptor 4 (TLR4) signaling pathway downstream related inflammatory factors.Methods:A prospective study method was used to select 90 elderly patients with PD with fluctuating symptoms who were admitted to the Eighth People′s Hospital of Hebei Province from June 2021 to October 2022 as research objects. The patients were divided into observation group and control group with 45 cases in each group according to random number table method. The observation group was treated with pentoxifylline sequential therapy combined with rasagiline and levodopa. The control group was treated with rasagiline combined with levodopa. The clinical efficacy of the two groups was compared. The unified Parkinson disease rating scale (UPDRS), Montreal cognitive assessment scale (MoCA), Berg balance scale (BBS) and 39-item Parkinson disease quality of life questionnaire (PDQ-39) were scored before and after treatment. Hemorheology indexes and serum levels of related inflammatory factors downstream of TLR4 signaling pathway, including whole blood high viscosity (HBV), whole blood low shear viscosity (LBV), plasma viscosity (PV), fibrinogen (FIB); TLR4, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF) -α, were detected before and after treatment in both groups. The adverse reactions of the two groups were compared.Results:The total effective rate in observation group was significantly higher than that in control group: 93.33% (42/45) vs. 77.78% (35/45), and there was statistical difference ( P<0.05). After treatment, the UPDRS mental activity and emotional disorders, daily living ability, motor function, motor complications scores and PDQ-39 score of the two groups were significantly lower than before treatment, the MoCA and BBS scores were significantly higher than before treatment, and the improvement was more significant in the observation group, there were statistical differences ( P<0.05). After treatment, HBV, LBV, PV and FIB in the observation group were significantly decreased compared with those before treatment: (6.52 ± 0.92) mPa·s vs. (7.25 ± 1.24) mPa·s, (11.45 ± 1.24) mPa·s vs. (14.13 ± 1.64) mPa·s, (1.55 ± 0.17) mPa·s vs. (1.88 ± 0.22) mPa·s, (3.25 ± 0.47) g/L vs. (3.82 ± 0.52) g/L, and there were statistical differences ( P<0.05). There were no significant differences in hemorheology indexes of control group before and after treatment ( P>0.05). After treatment, serum levels of TLR4, IL-1β, IL-6 and TNF-α in both groups were significantly decreased compared with those before treatment, and the indexes in observation group were significantly lower than those in control group: (2.07 ± 0.18) ng/L vs. (2.58 ± 0.21) ng/L, (1.42 ± 0.17) ng/L vs. (2.28 ± 0.25) ng/L, (1.56 ± 0.22) ng/L vs. (2.42 ± 0.28) ng/L, (46.31 ± 3.17) ng/L vs. (54.34 ± 3.65) ng/L, and the differences were statistically significant ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Pentoxifylline sequential therapy combined with rasagiline and levodopa can effectively improve the hemorheology of elderly patients with PD accompanied by symptom fluctuations, reduce the levels of related inflammatory factors downstream of serum TLR4 signaling pathway, and improve clinical efficacy.

Objective:To compare the effect of a 3D-printed ankle and foot orthosis (AFO) with that of a traditional AFO on the recovery of walking function after a stroke.Methods:Thirty-four hemiplegic stroke survivors were randomly divided into an observation group and a control group, each of 17. Both groups were taught good limb placement and given joint mobility, standing and walking training for 4 weeks wearing either a 3D-printed or a conventional AFO. Walking speed, walking endurance, and dynamic balance were evaluated before and after the experiment using the 10-metre walk test (10MWT), the 6-minute walk test (6MWT), and the timed up and go test (TUGT). Integrated electromyography (iEMG) was also performed on each subject′s bilateral rectus femoris, anterior tibialis, and gastrocnemius muscles during walking, and their healthy and affected side iEMG results were compared to assess the activation of the affected lower limb muscles.Results:After treatment, the 10MWT, 6MWT, and TUGT results of both groups had improved significantly, but the observation group′s average results were then significantly better than those in the control group. The iEMG disparities between the healthy and affected sides had also decreased significantly, but on average the disparities in the observation group were significantly smaller than in the control group.Conclusion:Both types of AFO can effectively improve the walking speed, walking endurance, and dynamic balance of hemiplegic stroke survivors and promote muscle activation in the affected lower limb. A 3D-printed AFO is relatively more effective.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objectives:This study aimed to assess the efficacy and safety of bendamustine in combination with rituximab (BR regimen) for the treatment of newly diagnosed indolent B-cell non-Hodgkin's lymphoma (B-iNHL) and elderly mantle cell lymphoma (eMCL) .Methods:From December 1, 2020 to September 10, 2022, a multi-center prospective study was conducted across ten Grade A tertiary hospitals in Shandong Province, China. The BR regimen was administered to evaluate its efficacy and safety in newly diagnosed B-iNHL and eMCL patients, and all completed at least four cycles of induction therapy.Results:The 72 enrolled patients with B-iNHL or MCL were aged 24-74 years, with a median age of 55 years. Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1 were observed in 76.4% of patients, while 23.6% had scores of 2. Disease distribution included follicular lymphoma (FL) (51.4% ), marginal zone lymphoma (MZL) (33.3% ), eMCL (11.1% ), and the unknown subtype (4.2% ). According to the Ann Arbor staging system, 16.7% and 65.3% of patients were diagnosed with stage Ⅲ and stage Ⅳ lymphomas, respectively. Following four cycles of BR induction therapy, the overall response rate was 98.6%, with a complete response (CR) rate of 83.3% and a partial response (PR) rate of 15.3%. Only one eMCL patient experienced disease progression during treatment, and only one FL patient experienced a relapse. Even when evaluated using CT alone, the CR rate was 63.9%, considering the differences between PET/CT and CT assessments. The median follow-up duration was 11 months (range: 4-22), with a PFS rate of 96.8% and an OS rate of 100.0%. The main hematologic adverse reactions included grade 3-4 leukopenia (27.8%, with febrile neutropenia observed in 8.3% of patients), grade 3-4 lymphopenia (23.6% ), grade 3-4 anemia (5.6% ), and grade 3-4 thrombocytopenia (4.2% ). The main non-hematologic adverse reactions such as fatigue, nausea/vomiting, rash, and infections occurred in less than 20.0% of patients.Conclusion:Within the scope of this clinical trial conducted in China, the BR regimen demonstrated efficacy and safety in treating newly diagnosed B-iNHL and eMCL patients.

Objective To investigate the effect of naringenin on the killing rate of natural killer (NK) cells and related mechanism by amplification of human peripheral blood mononuclear cells into NK cells in vitro and co-culture with hepatocellular carcinoma (HCC) CLC5 cells at a ratio of 1∶ 1. Methods A lymphocyte separation medium was used to isolate human peripheral blood mononuclear cells, which were induced with recombinant human interleukin-2 in vitro to culture NK cells. CCK-8 assay was used to measure the proliferation of HCC cells after human HCC cells were treated with naringenin (0, 3.125, 6.25, 12.5, 25, and 50 μmol/L) for 0, 24, and 48 hours, and after human NK cells were treated with different concentrations of naringenin for 24 hours, CCK-8 assay was used to measure the proliferation of NK cells. CellTiter-LumiTM was used to measure the killing rate of NK cells after the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours. Quantitative real-time PCR was used to measure the gene expression of the activating receptor NKG2D in NK cells and NKG2D ligands in HCC cells. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results After being induced and cultured by recombinant human interleukin-2, NK cells were amplified to 82.33%±0.70% of human peripheral blood mononuclear cells. After naringenin treatment for 24 hours, there was no significant difference in the proliferation rate of HCC CLC5 cells between all mass concentration groups (all P > 0.05), and in the 25 and 50 μmol/L mass concentration groups, naringenin significantly promoted the proliferation of NK cells (both P < 0.000 1). After the NK-HCC cell co-culture system at the ratio of 1∶ 1 was treated with naringenin for 24 hours, there was a significant increase in the killing rate of NK cells in the 25 and 50 μmol/L mass concentration groups (both P < 0.000 1). After the co-culture system was treated with naringenin for 24 hours, naringenin had no effect on the expression of NKG2D in NK cells in the 25 and 50 μmol/L mass concentration groups, and it also had no effect on the expression of MICB and ULBP2 in HCC cells (all P > 0.05); it significantly upregulated the expression of the NKG2D ligands such as ULBP1 and ULBP3 in HCC cells (all P < 0.001). Conclusion Naringenin may increase the killing activity of NK cells by upregulating the expression of NKG2D ligands in HCC cells.

Objective:To investigate the therapeutic effect of rat bone marrow mesenchymal stem cells (BMSCs) transfected with recombinant rat platelet-derived growth factor BB (rrPDGF-BB) gene on the distraction osteogenesis.Methods:From October, 2019 to June, 2020, 48 batches of BMSCs were cultured from 48 young SD rats, 24 of which were transfected with rrPDGF-BB gene by lentivirus. Meanwhile, other 72 male adult SD rats were randomly selected to establish the right femoral distraction osteogenesis model. The rats were equally divided into 3 groups. PBS, BMSCs without intervention and BMSCs transfected with rrPDGF-BB gene were injected into the distraction space of each group of rats assigned as Blank group, Negative group and Experimental group, respectively. Results of the experiment were evaluated by means of imaging and immunohistochemistry. P<0.05 indicated a statistically significant difference. Results:The cultured BMSCs grew well. The expression of CD34(0.1%) and CD45(2.8%) in the third generation of BMSCs was low, and that of CD29 (95.1%) was high, which was consistent with the phenotype of BMSCs described in literatures. After transfection, the expression of green fluorescence gradually increased with the extension of transfection time, confirming the success of transfection. After 14 days, all rats reached the expected distance of distraction. The rats were observed at assigned time points in 2, 4 and 8 weeks. The photos of femur specimen showed that continuous callus could be seen in the experimental group, the hardness and colour were close to the normal bone tissue, and the activity of the distraction space was poor, which was lower than that of the blank group. X-ray examination showed that there were more new callus in the experimental group, and the bone marrow cavity was re-canalized earlier than that of the blank group; Micro-CT examination, in sagittal plane, showed that the distraction space of the experimental group healed well, the broken end was connected, and the recanalization of bone marrow cavity was earlier than that of the blank group; Micro-CT parameters of each group showed that trabecular thickness[(0.297±0.005) mm], trabecular number [(1.663±0.032) mm], bone volume fraction[(59.832±2.187)%] and bone mineral density[(0.586±0.014) g/cm 3] of the experimental group were the greatest, while trabecular separation[(0.399±0.051) mm] of the experimental group was the smallest. There was statistical difference between each group( P < 0.05); HE staining and VEGF immunohistochemistry showed that the vessels and chondrocytes formed earlier and were more in the experimental group than that in the blank group. In 8 weeks, the new callus joined into one piece under the microscope in the experimental group, and the bone marrow cavity was re-canalized with a large number of red blood cells. Conclusion:Studies have shown that BMSCs transfected with rrPDGF-BB gene can promote the formation of callus in the distraction area of rats, shorten the mineralisation time of new callus, and promote the maturation of new bone in the area of distraction osteogenesis.

Reports of tuberculosis (TB) outbreaks among schoolchildren have increased in recent years in countries across the Western Pacific Region. Cases from China, Japan, Mongolia and the Republic of Korea were studied to derive lessons from the challenges and responses to TB outbreaks in schools. Despite differences in the TB burden and outbreak preparedness, the four countries reported similar challenges. These included delayed diagnosis of index cases, lack of experienced health professionals and sustained financial support, and difficulty in responding to intensified media and community attention. Early detection of outbreaks, established resource mobilization networks, coordination among stakeholders and proactive communication were highlights of successful outbreak responses. These principles could be adapted to each context for responses to future TB outbreaks in schools.