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

Objective To analyze the clinical value of rebabapide combined with famotidine in the treatment of postoperative ulcers in patients with early gastric cancer.Methods Postoperative ulcer patients with early gastric cancer were selected as the study objects,and were divided into control group and treatment group according to treatment plan using cohort method.Control group was orally treated with famotidine tablet 20 mg,bid;on the basis of the control group,the treatment group was orally treated with rebabapide capsule 0.1 g,tid,and both groups were treated for 4 weeks.The gastric mucosal morphological indexes,gastrointestinal hormone[vasoactive intestinal peptide(VIP),cholecystokinin(CCK),motilin(MTL),pepsinogen[pepsinogen Ⅰ(PG Ⅰ),pepsinogen Ⅱ(PG Ⅱ)]in the two groups were compared.Results There were 40 patients in the treatment group and control group.After treatment,the total clinical effective rate of the treatment group was 92.50％(37 cases/40 cases)and higher than that of the control group[75.00％(30 cases/40 cases)],and the difference was statistically significant(P＜0.05).After treatment,the scores of mucosal thickness in treatment group and control group were(0.22±0.08)and(0.51±0.10)points;the scores of inflammatory cell infiltration degree were(0.42±0.08)and(0.79±0.16)points;the scores of gland density were(0.80±0.12)and(1.16±0.27)points,respectively;mucosal morphology scores were 0.48±0.11 and 0.74±0.12;VIP were(16.78±2.49)and(19.46±3.02)ng·L-1;CCK were(55.38±58.47)and(71.48±10.38)ng·L-1,respectively;MTL were(82.19±14.52)and(97.68±11.58)pg·mL-1;PG Ⅰ were(168.74±17.42)and(136.78±15.44)ng·mL-1,respectively;PG Ⅱ were(16.42±2.50)and(20.58±3.79)ng·mL-1,respectively.Compared with control group,there were statistically significant differences in the above indexes in treatment groups(all P＜0.05).The incidence of adverse drug reactions in the treatment group was 15.00％(6 cases/40 cases)compared with 10.00％(4 cases/10 cases)in the control group,there was no statistical significance(P＞0.05).Conclusion Rebaptidine combined with famotidine is effective and safe in the treatment of postoperative ulcer patients with early gastric cancer.It can improve gastric mucosa morphological indexes,gastrointestinal hormones and pepsinogen.

OBJECTIVE To evaluate the consistency between the quetiapine LC-MS/MS kit and the laboratory-built method(reference method) in the detection results of quetiapine therapeutic drug monitoring. METHODS A total of 120 remaining plasma samples were collected from patients receiving quetiapine therapeutic drug monitoring from March to October in 2021. The plasma concentration of quetiapine was detected by kit and reference method respectively. The analysis of correlations and consistency was performed by outlier analysis, linear regression and Bland-Altman method. RESULTS No outliers were detected. The linear regression equation was Y=1.018X+4.400(r=0.998), indicating a good correlation. The Bland-Altman plot analysis showed good agreement between the two measurements. CONCLUSION The detection results of quetiapine LC-MS/MS kit and reference method are in good agreement. The kit can be used for clinical quetiapine treatment drug monitoring.

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 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.

【Objective】 To evaluate the clinical implications of ARL5B in esophageal cancer and its underlying mechanisms by using bioinformatics methods. 【Methods】 ARL5B transcriptomic expression data were obtained from The Cancer Genome Atlas (TCGA), R software was employed to detect the differential expression mRNAs, and related clinical information was collected for survival analysis. To validate the bioinformatics results, Real-time quantitative PCR (qRT-PCR) and Western blotting were carried out for clinical specimens of esophageal cancer tumor tissues and adjacent tissues. Immunohistochemistry was used to evaluate the expression of ARL5B and its associated clinicopathologic features. The underlying mechanisms of ARL5B in esophageal cancer were preliminarily explored by bioinformatics and qRT-PCR. 【Results】 Bioinformatics method showed that the expression of ARL5B in human esophageal cancer tissues was significantly higher than in adjacent tissues and correlated with poor prognosis. Clinical specimens were detected, the expressions of ARL5B mRNA and protein were the highest in metastases lymph node, followed by esophageal cancer tissues and adjacent tissues, which corresponded with bioinformatics results. The expression of ARL5B was strongly correlated with lymph node metastases and advanced clinical stage. Kaplan-Meier analysis results denoted high ARL5B level, indicating poor prognosis. Enrichment analysis showed that ARL5B was associated the biological processes such as vacuolar transport, late endosome to lysosome transport, and organelle localization. Protein-protein interaction analysis (PPI) suggested that ARL5B might interact with VPS16, KIF1A and TOM1, whose expressions were verified by qRT-PCR and positively correlated with ARL5B expression. 【Conclusion】 ARL5B was highly expressed in esophageal cancer and associated with lymph node metastases, advanced clinical stage, and poor prognosis. ARL5B may be involved in the progression of esophageal cancer with several molecular mechanisms.