BACKGROUND:Previous studies have found that neohesperidin can delay bone loss in ovariectomized mice and has the potential to treat osteoporosis,but its specific mechanism of action remains to be explored. OBJECTIVE:To explore the key targets and possible mechanisms of neohesperidin in the treatment of osteoporosis based on bioinformatics and cell experiments in vitro. METHODS:The gene expression dataset related to osteoporosis was obtained from GEO database,and the differentially expressed genes were screened and analyzed in R language.The osteoporosis-related targets were screened from GeneCards and DisGeNET databases,and the neohesperidin-related targets were screened from ChEMBL and PubChem databases,and the common targets were obtained by intersection of the three.The String database was used to construct the PPI network of intersection genes,and the key targets were screened.The DAVID database was used for GO and KEGG enrichment analysis.The AutoDock software was used to verify the molecular docking between the neohesperidin and the target protein.The effect of neohesperidin on osteogenic differentiation of C57 mouse bone marrow mesenchymal stem cells was detected.Complete medium was used as blank control group;osteogenic induction medium was used as the control group;and osteogenic induction medium containing different concentrations of neohesperidin(25,50 μmol/L)was used as experimental group.The expression of alkaline phosphatase,the degree of mineralization,the expression of osteogenic-related genes and target genes during osteogenic differentiation of cells were measured at corresponding time points. RESULTS AND CONCLUSION:(1)9 253 differentially expressed genes,2 161 osteoporosis-related targets,and 326 neohesperidin-related targets were screened.There were 53 common targets among the three.All 53 genes were up-regulated in osteoporosis samples.The PPI network screened the target gene PRKACA of research significance.GO function and KEGG pathway enrichment analysis showed that neohesperidin's treatment of osteoporosis through PRKACA target mainly depended on biological processes such as protein phosphorylation and protein autophosphorylation,acting on endocrine resistance,proteoglycan in cancer,and estrogen signaling pathway to play a therapeutic role.Molecular docking results showed that neohesperidin had a certain binding ability to the protein corresponding to the target PRKACA.(2)The results of alkaline phosphatase staining showed that neohesperidin could promote the expression of alkaline phosphatase in the early stage of osteogenic differentiation of mesenchymal stem cells.Alizarin red staining showed that neohesperidin could promote the mineralization of osteogenic differentiation of mesenchymal stem cells.RT-qPCR results showed that neohesperidin could increase the mRNA expression of alkaline phosphatase,PRKACA,and osteocalcin.(3)These results indicate that neohesperidin may promote osteogenic differentiation through PRKACA target on the estrogen signaling pathway to prevent and treat osteoporosis.

BACKGROUND: The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients. METHODS: 104 EGFR-mutated NSCLC-LM patients who received IP treatment at Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School from January 2018 to June 2024 were analyzed retrospectively. Clinical parameters, treatment regimens, and survival outcomes were collected. The overall survival (OS), progression-free survival (PFS), clinical response rate and adverse events (AEs) were evaluated. RESULTS: The cohort demonstrated a median PFS of 9.6 months and OS of 13.0 months with 6-month and 1-year OS rates of 80.8% and 56.5%, respectively. Clinical response was observed in 77.9% of patients. The common AEs were myelosuppression (58.7%) and elevation of hepatic aminotransferases (25.0%). Nine (8.7%) patients experienced grade 4 myelosuppression and recovered to normal after receiving symptomatic treatment. Subgroup analyses revealed prolonged OS in patients with Karnofsky performance status (KPS) ≥60 versus <60 (14.4 vs 9.0 months, P=0.0022) and those receiving Bevacizumab therapy versus not (19.2 vs 10.5 months, P=0.0011). CONCLUSIONS IP exhibits promising efficacy and manageable toxicity in EGFR-mutated NSCLC-LM patients. When combined with Bevacizumab, it exerts synergistic antitumor effects with the potential to further improve clinical outcomes.
Humans ; Pemetrexed/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Male ; Female ; Middle Aged ; Lung Neoplasms/pathology* ; ErbB Receptors/genetics* ; Aged ; Mutation ; Adult ; Retrospective Studies ; Injections, Spinal ; Meningeal Neoplasms/genetics* ; Treatment Outcome ; Aged, 80 and over

Objective To evaluate the malaria diagnostic capability in Shanghai Municipal Malaria Diagnostic Reference Laboratory from 2017 to 2022 and to analyze factors affecting the diagnosis results, so as to provide the scientific evidence for increasing the laboratory malaria diagnostic capability during the post-elimination stage. Methods Plasmodium-negative blood smears were randomly sampled using a proportional sampling method each quarter during the period from 2017 to 2022 and scored by Shanghai Municipal Malaria Diagnostic Reference Laboratory. Malaria cases’ blood samples from district centers for disease control and prevention in Shanghai Municipality were re-reviewed using microscopy and multiplex PCR assay to evaluate the capability of malaria diagnosis. Results A total of 7 746 quality control blood smears were collected from district centers for disease control and prevention in Shanghai Municipality from 2017 to 2022, with a mean score of (76.74 ± 14.34) points and a qualification rate of 86.65% (6 712/7 746). A total of 387 blood smears were re-reviewed from 2017 to 2022, with an overall coincidence of 96.38% (373/387) for malaria diagnosis and 95.06% (308/324) for parasite species identification, and there were no significant differences in the coincidence for either malaria diagnosis (χ² = 2.57, P > 0.05) or parasite species identification among years (χ² = 1.04, P > 0.05). A total of 384 whole blood samples were collected from district centers for disease control and prevention, and the detection of whole blood samples was 70.31% (270/384) in district centers for disease control and prevention. All 384 whole blood samples were re-reviewed by Shanghai Municipal Malaria Diagnostic Reference Laboratory using a multiplex PCR assay from 2017 to 2022, with an overall coincidence of 94.07% (254/270) for malaria diagnosis and 99.55% (223/224) for parasite species identification, and there were no significant differences in the coincidence for either malaria diagnosis (χ² = 5.77, P > 0.05) or parasite species identification among years (χ² = 8.37, P > 0.05). The overall coincidence rates of Plasmodium-positive and negative whole blood samples were 100.00% (224/224) and 65.22% (30/46) in district centers for disease control and prevention, with a significant difference (χ² = 82.82, P < 0.001), and there was a significant difference in the coincidence rate for identification of P. falciparum, P. vivax, P. malariae and P. ovale (χ² = 24.28, P < 0.001). A total of 1 584 blind blood smears subjected to microscopic examinations by centers for disease control and prevention and medical institutions across all districts in Shanghai Municipality from 2017 to 2022, with a 96.15% (1 523/1 584) correct rate for malaria diagnosis and 85.07% (1 003/1 179) for parasite species identification, and there were significant differences in the correct rate of both malaria diagnosis (χ² = 20.98, P < 0.001) and parasite species identification among years (χ² = 70.77, P < 0.001). A total of 320 blind nucleic acid samples from malaria cases were tested, with a 99.38% (318/320) correct rate for malaria diagnosis and 100.00% (225/225) for parasite species identification, and there was no significant difference in the correct rate of malaria diagnosis among years (χ² = 6.04, P > 0.05). Conclusions There were still shortcomings in blood smears preparation, microscopic examinations and nucleic acid testing in centers for disease control and prevention across all districts in Shanghai Municipality from 2017 to 2022. A greater role in the quality control of malaria diagnosis is recommended for Shanghai Municipal Malaria Diagnostic Reference Laboratory to prevent the re-establishment of imported malaria and consolidate the elimination achievements.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

Objective: To compare the effects of aerobic exercise, resistance training, and a combination of aerobic exercise and resistance training (combined exercise) with dietary restrictions on inflammatory factors and gut microbiota in obese children, so as to provide the reference for improving the health level of obese children. Methods: From August to September 2022, a total of 70 obese children aged 10-12 from the Affiliated Experimental Primary School of Minjiang Normal University were recruited through online notifications and WeChat distribution through parent groups. Participants were divided into dietary restriction (DR, n=18) group, aerobic exercise combined with dietary restriction (AE+DR, n=18) group, resistance training combined with dietary restriction (RT+DR, n=17) group and combined exercise combined with dietary restriction (ART+DR, n=17) group,through random number table method. From September to November 2022, each group received different interventions.The daily dietary intake of calories in the DR group was determined according to resting energy consumption. The AE+DR group intervention mainly included skipping rope, aerobics exercises, jogging and sports games, and were maintained for each session lasting 50 minutes. For RT+DR group, the exercise intensity of resistance training was (65%-85%) maximum strength, with a total of 10 actions. The ART+DR group included resistance training (20 minutes), aerobic exercise (20 minutes), preparation and relaxation phases for 5 minutes each. The DR and exercise intervention was administered for 8 weeks (4 times a week for Monday, Tuesday, Thursday and Friday). Before and after different intervention methods, serum inflammatory factors were detected by enzymelinked immunosorbent assay (ELISA) and intestinal flora was calculated by plate colony counting method. Results: Compared to those before intervention, the levels of serum TNF-α, IL-6 and CRP, and the contents of enterococcus and escherichia coli in the faeces significantly decreased, while the contents of lactobacillus and bifidobacterium in the faeces significantly increased after intervention (t=7.19，7.15，4.57，5.42，5.15，-3.51，-7.30；5.14，3.64，3.02，3.27，5.00，-3.09，-3.75；7.10，10.86，7.74，10.92，9.26，-6.63，-6.33，P<0.05) in AE+DR, RT+DR and ART+DR groups. The levels of serum TNF-α and CRP and enterococcus decreased significantly, and the contents of lactobacillus and bifidobacterium in the faeces increased significantly after intervention (t=2.74, 2.22, 2.14, -2.21, -2.81, P<0.05) in the DR Group. After 8 weeks of intervention with different methods, the change differences of enterococcus, escherichia coli, lactobacillus, bifidobacterium in the faeces, and serum TNF-α, IL-6 and CRP levels were statistically significantin the four groups of obese children (H=22.22, 23.75, 13.44, 28.33, 18.02, 33.64, 25.14, P<0.01). In addition, the decreases of enterococcus in the faeces and serum TNF-α, IL-6, CRP levels, and the increases of lactobacillus in the faeces were significantly higher than those in the other three groups. Conclusions Dietary restriction alone or combined with different exercises bring beneficial changes in the inflammatory factors and gut microbiota indicators in obese children. Combined exercise,as well as aerobic exercise combined with dietary restrictions are more reasonable and effective in obese children.

Objective:To construct prediction models of necrotizing enterocolitis (NEC) using machine learning (ML) methods.Methods:From January 2015 to October 2021, neonates with suspected NEC symptoms receiving abdominal ultrasound examinations in our hospital were retrospectively analyzed. The neonates were assigned into NEC group (modified Bell's staging≥Ⅱ) and non-NEC group for diagnostic prediction analysis (dataset 1). The NEC group was subgrouped into surgical NEC group (staging≥Ⅲ) and conservative NEC group for severity analysis (dataset 2). Feature selection algorithms including extremely randomized trees, elastic net and recursive feature elimination were used to screen all variables. The diagnostic and severity prediction models for NEC were established using logistic regression, support vector machine (SVM), random forest, light gradient boosting machine and other ML methods. The performances of different models were evaluated using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, negative predictive value and positive predictive value.Results:A total of 536 neonates were enrolled, including 234 in the NEC group and 302 in the non-NEC group (dataset 1).70 were in the surgical NEC group and 164 in the conservative NEC group (dataset 2). The variables selected by extremely randomized trees showed the best predictive performance in two datasets. For diagnostic prediction models, the SVM model had the best predictive performance, with AUC of 0.932 (95% CI 0.891-0.973) and accuracy of 0.844 (95% CI 0.793-0.895). A total of 11 predictive variables were determined, including portal venous gas, intestinal dilation, neutrophil percentage and absolute monocyte count at the onset of illness. For NEC severity prediction models, the SVM model showed the best predictive performance, with AUC of 0.835 (95% CI 0.737-0.933) and accuracy of 0.787 (95% CI 0.703-0.871). A total of 25 predictive variables were identified, including age of onset, C-reactive protein and absolute neutrophil count at clincial onset. Conclusions:NEC prediction model established using feature selection algorithm and SVM classification model in ML is helpful for the diagnosis of NEC and grading of disease severity.

In order to promote the development of hair transplantation, particularly the establishment of standards, the Hair Transplantation Expert Group of Plastic and Aesthetic National Medical Quality Control Center invited experts in the field of hair transplantation across China and formed a draft of the Expert Consensus on Standard Terminology for Hair Transplantation based on the collation of relevant literature and monographs. By combining Delphi methodology and consensus meetings, the expert group conducted several rounds of consultations on issues such as follicular unit anatomy, harvesting, dissection, and implantation, ultimately presenting 54 terminologies. This consensus considers the original Chinese and English meanings as well as the professional characteristics of terms used in hair transplantation, highlights the unique features and advantages of hair transplantation, and preserves its essence while promoting innovation, with the hope of providing valuable reference for clinical researchers engaged in hair transplantation both domestically and internationally, and better facilitating the standardization and advancement of the field.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.