Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

AIM: To investigate the mechanism of Hexue Mingmu Tablets(HXMMT)in improving diabetic retinopathy(DR)based on transcriptomics.METHODS: Zebrafish DR models were established by 3-day glucose induction(130 mmol/L)starting at 3 days post-fertilization(dpf). Larvae were randomized into four groups: control group(CG; aquaculture water), model group(MG; 130 mmol/L glucose), low-dose HXMMT treatment group(L-HX; 130 mmol/L glucose +7.5 mg/L HXMMT), and high-dose HXMMT treatment group(H-HX; 130 mmol/L glucose +75 mg/L HXMMT), with a 3-day intervention period until 6 dpf. The area and length of eyes, and body length of zebrafish were observed by stereomicroscopy, retinal morphology was observed by hematoxylin-eosin staining(HE), and retinal vessel diameter was observed under fluorescence microscope. Differentially expressed genes(DEGs)were identified by RNA-sequencing(RNA-seq)technology to further elucidate the molecular mechanism of HXMMT in improving DR in zebrafish, and the sequencing accuracy was validated through quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS: HE staining demonstrated that the intervention with HXMMT significantly improved the disordered cell arrangement, widened gaps, and thickened inner nuclear layer(INL)in ganglion cell layer GCL); retinal vascular diameter quantification revealed that the retinal vessel diameter of the MG significantly increased compared with the CG, and it was significantly changed after the intervention of HXMMT, with significant efficacy in the H-HX(P<0.05); transcriptomics profiling identified 1 470 reversed DEGs, predominantly enriched in the AMPK signaling pathway, FoxO signaling pathway, retinal developmental processes, and tight junction regulation. Technical validation confirmed strong correlation between qRT-PCR and RNA-seq data(R2=0.8571, P<0.05).CONCLUSION: HXMMT may improve retinal vascular microcirculation disorders in DR by regulating core targets including vsx1, pde6c, arr3a, plk1, fbp1b, foxo1a, pcna, and cdk1, as well as synergistically modulating processes such as retinal development in camera-type eyes, visual perception, microtubule cytoskeletal organization, tight junctions, and the AMPK signaling pathway, Foxo signaling pathway.

Meropenem （MEM） is one of the important drugs for the treatment of severe infections， but the standard dose is often difficult to achieve an effective therapeutic concentration target. This article reviews the related studies on the population pharmacokinetics of MEM in patients with severe infection. It is found that the apparent volume of distribution （Vd） and clearance rate are the most important factors affecting the dose adjustment， and the factors affecting Vd include serum albumin， age， overall weight， shock status， and chest/abdomen/cerebrospinal fluid drainage. The main factors affecting the clearance rate were renal function， renal replacement therapy treatment mode and combination therapy. For adult patients with severe infections in China， MEM is recommended to be administered in an individualized manner based on glomerular filtration rate， with a dosage range of 500 to 1 500 mg given every 4 to 6 hours， and prolonged infusion is preferred. When the minimum inhibitory concentration （MIC） of the pathogenic bacteria reaches 64 mg/L， therapeutic drug monitoring is required. For therapeutic efficacy， it is essential to ensure that the trough concentration remains above the MIC； to prevent drug resistance， it should be maintained above 4×MIC. Regarding safety， it is recommended that the upper limit of the trough concentration be 32 mg/L， and blood sampling for monitoring can be conducted as early as after 1 to 2 doses of administration.

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

With the continuous innovation of genomics,proteomics and molecular biological detection technol-ogy,the treatment of non-small cell lung cancer(NSCLC)has changed from traditional chemotherapy to immunotherapy and targeted therapy.Among them,molecular tumor markers targeting tyrosine kinase pathways play more important roles in clinical practice.For advanced NSCLC patients with positive epidermal growth factor receptor(EGFR)mutations,there are many first-line drugs on the market and they could bring significant efficacy,thus completely subverting the treatment pattern of advanced NSCLC.Common mutations of EGFR in Chinese patients are located on exons 19,20 and 21,of which exons 19 and 21 mutations are the more common types.Besides,there is also a subtype of EGFR mutations,known as EGFR 20 exon insertion(EGFR 20ins)mutation.The authors summarized the treatment of a lung adenocarcinoma patient with EGFR 20ins mutation accepting Furmonertinib mesylate,in order to provide effective references for clinical diagnosis and treatment.

Objective:To explore the efficacy and safety of tetrandrine in the treatment of rheumatoid arthritis.Methods:Randomized controlled studies of tetrandrine in the treatment of rheumatoid arthritis were searched in CNKI,VIP,Wanfang database,SinoMed,PubMed,Springer,Web of Science and Cochrane Central Register of Controlled Trails databases.A meta-analysis was conducted using R 3.5.3 software to evaluate the clinical outcomes,including the total effective rate,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF),visual analogue scale(VAS),disease activity score(DAS),tender joint count(TJC),swollen joint count(SJC),and morning stiffness duration,as well as adverse events of rheumatoid arthritis patients.Results:A total of 10 articles were included in the study.The meta-analysis indicated that tetrandrine significantly improved the total effective rate(OR=3.27,95%CI:2.01-5.37,P<0.01),ESR(SMD=1.12,95%CI:0.06-2.19,P<0.05),CRP(SMD=0.75,95%CI:0.28-1.22,P<0.01),VAS(SMD=0.64,95%CI:0.29-1.00,P<0.01),TJC(SMD=1.16,95%CI:0.58-1.74,P<0.01),SJC(SMD=0.85,95%CI:0.40-1.31,P<0.01),and morning stiffness(SMD=1.09,95%CI:0.68-1.50,P<0.01).However,no statistical significance was found in RF(SMD=1.70,95%CI:-1.10-4.51,P>0.05)and DAS(SMD=0.26,95%CI:-0.59-1.11,P>0.05).The overall incidence of adverse events associated with tetrandrine treatment for rheumatoid arthritis was 20%(95%CI:12%-27%,I2=60%,P<0.05),with mild severity and favorable outcomes.Conclusion:Tetrandrine is effective in the treatment of RA patients with a mild degree of adverse events.

Objective To observe the expression levels and related mechanisms of miR-34a and its inflammatory-related factors in broncho-alveolar lavage fluid of patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods Totally 20 patients with acute exacerbation of COPD were recruited as the study group and 20 patients in stable period of COPD were recruited as control group.Bronchoalveolar lavage fluid was collected,A549 cell was cultured and AECOPD cell model was built for evaluating the effects of over-expression of miR-34a,inhibition of miR-34a,and silencing of HIF-1α in cells.ELISA assay was applied to detect the expression of inflammatory factors IL-6,IL-8,TNF-αand TGF-β in bronchoalveolar lavage fluid and cell supernatant.The expression of miR-34a and HIF-1 αwere measured by RT-qPCR,and Western blot was used to detect the expres-sion of HIF-1α.Results Compared with the control group,the expression of inflammatory factors,miR-34a,and HIF-1α in the AECOPD group were significantly elevated(P＜0.05).Over-expression of miR-34a led to further elevation of HIF-1α and inflammatory factor expression(P＜0.05).Inhibition of miR-34a resulted in a significant decrease of HIF-1α and inflammatory factors(P＜0.05).The expression of HIF-1α in the AECOPD group was significantly elevated(P＜0.05),and silencing HIF-1α significantly reduced the expression of inflam-matory factors(P＜0.05).The expression of miR-34a had no significant change.Conclusions miR-34a is in-volved in the inflammatory damage in patients with acute exacerbation of COPD by regulating HIF-1α.Interfering with the miR-34a/HIF-1α pathway alleviates inflammatory response,so it is a potential target in the treatment of acute exacerbation of COPD.

Objective To analyze the effect of endoscopic tumor resection by submucosal tunnel(STER)on recurrence in patients with submucosal tumors(SMT)around cardia.Methods A total of 92 patients with SMT around cardia were selected and divided into the treatment group(n=46)and the control group(n=46)using random number table method.The treatment group and the control group were treated with STER and endoscopic submucosal dissection(ESD),respectively,and both groups were followed up for 12 months after surgery.Periop-erative indexes,therapeutic effects,quality of life,sleep,inflammatory indexes,immune indexes before and 1 week after surgery,complications 1 week after surgery,recurrence 12 months after surgery were compared between the two groups.Results Compared with the control group,the surgery time of the treatment group was longer,the hospital stay was shorter and treatment cost were lower,and the stripping speed was faster(P＜0.05).Compared with before surgery,scores of Pittsburgh sleep Quality index(PSQI),serum levels of interleukin-8(IL-8),inter-leukin-6(IL-6),high-sensitive C-reactive protein(hs-CRP)and whole blood levels of CD8+decreased in the two groups 1 week after surgery,and the levels were lower in the treatment group(P＜0.05).Compared with the preoperative results,the levels of whole blood CD4+and CD4+/CD8+,scores of Quality of Life Core 46 Questionnaire(QLQ-C46),Karnofsky Score(KPS)were higher in the two groups 1 week after surgery,those in the treatment group was higher(P＜0.05).1 week after surgery,the complication rate of the two groups was lower in the treat-ment group(P＜0.05),and 12 months after surgery,the recurrence rate of the two groups was not statistically significant(P＞0.05).Conclusion STER treatment for SMT around cardia was highly effective,resulting in superior perioperative outcomes,enhanced life and sleep quality,reduced systemic inflammation,and bolstered immune function.Moreover,it significantly lowered the risk of complications without raising the rates of recurrence.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

OBJECTIVE To evaluate the efficacy and safety of dimethyl fumarate （DMF） in the treatment of multiple sclerosis （MS）. METHODS Retrieved from CBM， Web of Science， PubMed， the Cochrane Library， Embase， CNKI， Wanfang Data， and VIP， randomized controlled trials （RCTs） about DMF （trial group） versus other drugs or placebo （control group） were collected. After data screening and extraction， quality evaluation， meta-analysis was conducted by using RevMan 5.3 software. RESULTS A total of 6 literature were included， involving 638 patients. Results of meta-analysis showed that the proportion of patients with lesion changes after treatment in the trial group was lower than control group [MD＝－0.65， 95%CI（－1.27， －0.02）， P＝0.04]； there was no statistical significance in recurrence rate [RR＝1.06， 95%CI（0.52，2.17）， P＝0.88]， the proportion of patients with new lesions after treatment [RR＝1.05， 95%CI（0.62，1.80）， P＝0.85]， expanded disability status scale after treatment [MD＝0.02，95%CI （－0.18， 0.23）， P＝0.82]， the incidence of adverse events [RR＝1.33， 95%CI（0.97， 1.84）， P＝0.08] or severe adverse events [RR＝0.95，95%CI（0.48，1.90），P＝0.89] between 2 groups. Results of sensitivity analysis showed the study obtained unstable recurrence rate and the incidence of adverse events， while other results were robust. CONCLUSIONS DMF can control the lesion progression in MS patients to some extent and doesn’t increase the incidence of adverse events and serious adverse events， but there is no significant advantage in reducing the recurrence rate and controlling the disability progression.