OBJECTIVE: To explore the clinical efficacy of orthopedic manipulation combined with daoyin exercises in the treatment of chronic lumbar disc herniation under the guidance of the theory of "equal emphasis on muscles and bones". METHODS: A total of 60 patients with single-segment, unilateral chronic lumbar disc herniation from January 2023 to January 2024 were randomly divided into the traditional physical therapy group and the manipulation treatment group, with 30 cases in each group. Among them, 3 cases were lost to follow-up in the traditional physical therapy group and 2 cases in the manipulation treatment group. There were 27 cases in the traditional physical therapy group, including 15 males and 12 females, aged 25 to 65 years old with an average of (51.96±14.42) years;the course of disease ranged from 3 to 15 months with an average of (9.89±3.32) months;11 cases were on the left side and 16 cases on the right side;15 cases were at the L4, 5 segment and 12 cases at the L5S1 segment. They were treated with lumbar traction, medium-frequency electrical stimulation and ultrasonic therapy. There were 28 cases in the manipulation treatment group, including 14 males and 14 females, aged 24 to 68 years old with an average of (49.82±14.85) years old;the course of disease ranged from 3 to 14 months with an average of (9.61±3.05) months;15 cases were on the left side and 13 cases on the right side;17 cases were at the L4, 5 segment and 11 cases at the L5S1 segment. They were treated with orthopedic manipulation combined with daoyin exercises. The visual analogue scale (VAS), Oswestry disability index (ODI) and bilateral erector spinae muscle tone were compared between the two groups before treatment, after 2 weeks and 4 weeks of treatment. RESULTS: The two groups of patients were followed up and evaluated before treatment, 2 weeks and 4 weeks after treatment. The VAS of the manipulation treatment group and the traditional physical therapy group decreased from (5.46±0.99) and (5.41±1.05) points before treatment to (1.75±0.79) and (2.29±0.82) points after 4 weeks of treatment, respectively. Both groups were significantly improved after treatment compared with before treatment, and the differences were statistically significant (P<0.05);and the manipulation treatment group was better than the traditional physical therapy group at 4 weeks of treatment, with a statistically significant difference (P<0.05). The ODI of the manipulation treatment group and the traditional physical therapy group before treatment was (20.25±2.72) and (18.96±2.52) points, respectively, which decreased to (15.46±1.88) and (16.56±2.01) points after 2 weeks of treatment, and to (11.54±1.23) and (12.85±1.72) points after 4 weeks of treatment. Both groups were significantly improved after treatment compared with before treatment, and the differences were statistically significant (P<0.05), and the ODI in the manipulation treatment group was better than that in the traditional physical therapy group after treatment (P<0.05). There was no significant statistical difference in the displacement of erector spinae muscle tone between the healthy side and the affected side in both the manipulation treatment group and the traditional physical therapy group before treatment (P>0.05). After 2 weeks of treatment, the displacement values of erector spinae muscle tone on the healthy side in the manipulation treatment group and the traditional physical therapy group were (6.68±0.81) mm and (6.45±0.65) mm, respectively, and those on the affected side were (5.87±0.82) mm and (5.61±0.84) mm, respectively. After 4 weeks of treatment, the displacement values of erector spinae muscle tone on the healthy side in the manipulation treatment group and the traditional physical therapy group were (7.51±0.75) mm and (7.04±0.63) mm, respectively, and those on the affected side were (6.87±0.78) mm and (6.33±0.82) mm, respectively. The displacement values of erector spinae muscle tone on both the healthy and affected sides in both groups were significantly higher than those before treatment, and the differences were statistically significant (P<0.05);the displacement of erector spinae muscle tone in the manipulation treatment group after 4 weeks of treatment was better than that in the traditional physical therapy group, with a statistically significant difference (P<0.05). CONCLUSION Orthopedic manipulation combined with daoyin exercises can effectively improve the symptoms and lumbar function of patients with chronic lumbar disc herniation, and has more advantages in improving the tone of the erector spinae muscle.
Humans ; Male ; Female ; Middle Aged ; Adult ; Intervertebral Disc Displacement/physiopathology* ; Aged ; Lumbar Vertebrae/injuries* ; Exercise Therapy ; Chronic Disease/therapy* ; Manipulation, Orthopedic ; Combined Modality Therapy

OBJECTIVES: To investigate the application value of targeted next-generation sequencing (tNGS) in the etiological diagnosis of moderate to severe respiratory distress syndrome (RDS) in neonates. METHODS: A prospective randomized controlled trial was conducted, enrolling 81 term and late-preterm neonates with moderate to severe RDS admitted to Fujian Children's Hospital between December 2023 and December 2024. Patients were randomly assigned to the conventional microbiological test (CMT) group (n=42) or the tNGS group (n=39). For routine pathogen detection, bronchoalveolar lavage fluid was obtained via bronchoscopy, and lower respiratory tract specimens were collected via the endotracheal tube; all specimens underwent culture, and some specimens additionally underwent polymerase chain reaction or antigen testing. In the tNGS group, tNGS was performed in addition to routine pathogen detection on the same specimen types. The detection rate of pathogens, the detection rate of co-infections, and the duration of antibiotic use were compared between the two groups. RESULTS: The pathogen detection rate in the tNGS group (18/39, 46%) was significantly higher than that in the CMT group (8/42, 19%) (P=0.009). The co-infection detection rate was 13% (5/39) in the tNGS group, while no co-infections were identified in the CMT group (P=0.024). Regarding treatment, the duration of antibiotic use in the tNGS group was shorter than that in the CMT group [(12±4) days vs (15±5) days, P=0.003]. CONCLUSIONS tNGS significantly improves the pathogen detection rate in neonates with moderate to severe RDS and offers advantages in the rapid identification of co-infections and reduction of antibiotic treatment duration, suggesting it has clinical utility and potential for wider adoption.
Humans ; Prospective Studies ; Infant, Newborn ; Female ; Respiratory Distress Syndrome, Newborn/etiology* ; Male ; High-Throughput Nucleotide Sequencing/methods*

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVES: To evaluate whether adding Fuzheng Jiedu Xiaoji (FZJDXJ) therapy improves survival in advanced hepatitis B virus-related HCC (HBV-HCC) patients. METHODS: This prospective, randomized controlled study was performed at a major academic medical center in Beijing, China from October 2020 to October 2022. Eligible patients with advanced HBV-HCC were randomly divided equally (1:1) to receive either the combination of FZJDXJ and conventional Western medical therapy (63 cases, FZJDXJ group) or solely Western medicine (66 cases, control group). The study endpoints consisted of overall survival (OS) as the primary outcome, with progression-free survival (PFS), disease control rate (DCR), and adverse events (AEs) as secondary measures. RESULTS: The median OS was significantly prolonged in the FZJDXJ group at 8.9 months (95% CI: 6.0-11.9) vs. 4.4 months (95% CI: 3.2-7.3) in the control group (P<0.05). The hazard ratio for mortality in the FZJDXJ group was 0.59 (95% CI: 0.40-0.89), suggesting a 41% lower risk of death compared to the control group. The results revealed that patients receiving FZJDXJ therapy achieved a PFS of 5.1 months (95% CI: 4.1 to 7.2 months), compared to only 2.9 months (95% CI: 2.0 to 4.6 months) in the control group (P<0.05). Additionally, DCR was significantly elevated in the FZJDXJ group (20.6%) compared to the control group (10.6%, P<0.05). Subgroup analysis demonstrated that FZJDXJ significantly improved OS in patients with alpha-fetoprotein levels <400 ng/mL, age <60 years, Barcelona Clinic Liver Cancer (BCLC) stage C, and compensated liver function (Child-Pugh A and B, P<0.05). Multivariate analysis revealed that FZJDXJ therapy acted as an independent factor protecting against mortality within 1 year. Gastrointestinal symptoms are rare side effects, and no fatalities associated with the treatment were reported. CONCLUSION This randomized controlled trial demonstrated that FZJDXJ combined Western conventional therapy significantly improves OS and PFS in patients with advanced HBV-HCC. (registration No. ChiCTR2000033941).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/virology* ; Carcinoma, Hepatocellular/virology* ; Treatment Outcome ; Hepatitis B virus ; Adult ; Aged ; Hepatitis B/drug therapy*

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

Purpose To investigate the expression of LAMB3 and ITGB4 in esophageal squamous cell carcinoma(ESCC)and analyze their associations with clinicopathological features.Methods Bioinformatics was used to assess the expression of LAMB3 and ITGB4 in pan-cancer and ESCC.Immunohistochemistry was performed to evaluate their expression and distribution in ESCC tissues,and correlations clinicopathological features were analyzed.Follow-up data were collected to construct Kaplan-Meier survival curves,and Cox regression analysis was proformed to determine their prognostic significance.Results Bioinformatics analysis showed that LAMB3 and ITGB4 were highly expressed in ES-CC tissues(P＜0.001).Immunohistochemistry confirmed that both proteins were localized in the cytoplasm and membrane of tumor cells.High LAMB3 expression was significantly associated with poor differentiation(P＜0.001),lymph node metastasis(P=0.015),and T staging(P＜0.001).High ITGB4 expression was significantly correlated with poor differentiation(P=0.004)and advanced T staging(P=0.004).Cox regression analysis identified high ex-pression of LAMB3 and ITGB4 as independent prognostic factors for overall survival[HR=4.97(95％CI:2.73-9.02);HR=2.33(95％CI:1.36-3.99)].Conclusion LAMB3 and ITGB4 are highly expressed in ESCC.High LAMB3 expression is associated with tumor differentiation,lymph node metastasis,and T staging,while high ITGB4 expression is correlated with tumor differentiation and T staging.Patients with high expression of LAMB3 or ITGB4 have poorer overall survival,suggesting that these proteins may serve as prognostic biomarkers for unfavorable outcome in ESCC.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Previous studies have shown that the diversity and composition of intestinal microbiota are related to the effect of tumor immunotherapy,but the mechanism of intestinal microbiota affecting tumor immunotherapy resistance has rarely been sum-marized.This article not only expounds the current clinical sta-tus of tumor immunotherapy resistance,but also summarizes the correlation and regulatory mechanism between the composition and homeostasis of intestinal microbiota and drug resistance to different types of tumor immunotherapy,so as to provide a refer-ence for the study of potential targets for improving tumor immu-notherapy resistance based on intestinal microbiota.