To analyze the treatment strategy for a 78-year-old female patient with mismatch repair deficient (dMMR) gastric cancer who achieved long-term survival. After third-line chemotherapy failed, gene testing showed ARID1A p.Gln748fs, c.2733-1G＞T variation, with PD-L1 TPS 30%, CPS 60%. The nivolumab was employed, and two weeks later, the best response was partial response (PR). During the fourth-line immunotherapy maintenance treatment, progression of left adrenal metastasis was observed. The expression of human epidermal growth factor receptor-2 (HER-2) was positive, and the antibody drug conjugate disitamab vedotin (RC48) was chosen for treatment. After 10 months of treatment with nivolumab combined with RC48, the best efficacy was assessed as stable disease (SD), with a progression free survival (PFS) of up to 12 months. Radiotherapy was employed, and immunotherapy was maintained, allowing the patient to achieve a PFS of 18 months again. During immunotherapy, a clinical pharmacist developed a personalized pharmaceutical care plan for this patient. At the last follow-up, this patient achieved 78 months of long-term survival.

In the era of informatization, virtual teaching labs have emerged as a pivotal exploration in the construction of new teaching organizations at the primary level. Virtual labs of teaching research and reform require faculty members to collaboratively conduct teaching reform research and practice, thereby fostering new paradigms and achievements for teaching reforms. It serves as a vital foundation for supporting comprehensive reforms in curriculum teaching and specialty construction. This paper delves into the logical framework of virtual teaching research and reform labs from four dimensions (value orientation, construction principles, organizational structure, and operational safeguards), and elaborates on lab construction pathways from four aspects (technological platforms, behavioral relationships, knowledge management, and spiritual culture). Taking virtual teaching labs for medical education as an example, the paper summarizes practical experience in the innovative exploration of reform-oriented virtual teaching labs. Finally, we discuss the most constraining factors in the current construction of virtual teaching labs, and propose that research on virtual teaching labs should pay more attention to solving practical problems in major and curriculum reforms to promote the integration of medical education and practice, ultimately contributing to the realization of the Healthy China initiative.

OBJECTIVE: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis. METHODS: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis. RESULTS: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2^-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2^-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2^-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05). CONCLUSIONS BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans ; Histones ; Caspase 1 ; Large-Conductance Calcium-Activated Potassium Channels ; Lipopolysaccharides ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; L-Lactate Dehydrogenase ; Sepsis ; RNA, Small Interfering ; Caspases

OBJECTIVE: To detecte the carrying rate, the type and distribution of α-Thalassemia gene mutation in Honghe Prefecture, Yunnan Province, and analyze the differences in average erythrocyte volume (MCV), mean erythrocyte hemoglobin content (MCH) and hemoglobin among different types of α-Thalassemia. METHODS: The DNA samples from small cell hypochromic carriers or anemia patients and women of childbearing age who underwent hematological screening in The First People's Hospital of Honghe State was from 2015 to 2019 were enrolled and analyzed, and the mutation types and frequency of alpha-thalassemia positive rate were diagnosed by PCR reverse dot blot or PCR fluorescence dissolution curve. RESULTS: Among the 1 016 samples, 141(13.88%) of the patients were diagnosed as α-thalassemia. The α-thalassemia was subdivided into 3 types, silent (36.17%), minor (51.77%), and HbH disease (12.06%), and the MCV, MCH and HB levels were detected and showed a obvious decrease trend with significant difference (P < 0.05). The gene mutation types were 9 kinds, the deletion type gene was mainly --SEA (51.06%), followed by -α CONCLUSION Alpha-thalassemia in Honghe prefecture of Yunnan Province shows complex genetic diversity and significant genetic heterogeneity, and the mainly type of gene mutation is --SEA and --
China ; Female ; Genotype ; Heterozygote ; Humans ; Mutation ; alpha-Thalassemia/genetics* ; beta-Thalassemia

PURPOSE: Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone. METHODS: From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests. RESULTS: A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ CONCLUSION PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.
Adult ; Aged ; Aged, 80 and over ; Altitude ; China ; Decompressive Craniectomy ; Drainage ; Encephalocele/surgery* ; Hematoma ; Humans ; Intracranial Hemorrhage, Hypertensive/surgery* ; Middle Aged ; Prognosis ; Punctures ; Retrospective Studies ; Treatment Outcome

Objective:To explore the sense of coherence in the main caregivers of cancer patients, analyze its influencing factors, and explore the relationship between sense of coherence and care burden.Methods:From March 2018 to March 2019, convenience sampling method was used to select the main caregivers of 229 cancer patients admitted to two ClassⅢ Grade A hospitals in Harbin as the research object. The questionnaire survey was conducted with the General Information Questionnaire, Sense of Coherence Scale (SOC-13) and the Family Caregiver Burden Scale. Statistical analysis was carried out with t test, single factor analysis of variance, Pearson correlation as well as multiple linear regression. A total of 237 questionnaires were issued and 229 valid questionnaires were returned, with an effective recovery rate of 96.62%. Results:The score of sense of coherence in main caregivers of cancer patients was (55.67±9.23) , which was at a low level. The results of univariate analysis showed that there were statistically significant differences in the score of sense of coherence in main caregivers of cancer patients with different genders of caregivers, occupational status of caregivers, medical cost burden status, patient self-care level, and cumulative care time ( P<0.05) . The results of Pearson correlation analysis showed that the score of sense of coherence in main caregivers of cancer patients was positively correlated with the care burden score of the terminal cancer ( r=0.398, P<0.01) . The results of multiple linear regression analysis showed that the burden of medical expenses, the degree of self-care ability of patients, the cumulative care time, and the care burden of end-of-cancer (physical and mental burden, economic burden, life burden) were the main influencing factors of the sense of coherence in the main caregivers of cancer patients ( P<0.05) , which explained 32.2% variation of the sense of coherence. Conclusions:The main caregivers of cancer patients have a low level of sense of coherence and are affected by many factors. Clinical medical and nursing staff can carry out targeted interventions from patients, caregivers, society and other aspects to enhance the sense of coherence of the main caregivers, thereby improving the quality of life of patients and their main caregivers.

BACKGROUNDAn zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resource-limited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings.

METHODSThis prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96.

RESULTSIn terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19-2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences.

CONCLUSIONAZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; HIV Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stavudine ; administration & dosage ; adverse effects ; therapeutic use ; Zidovudine ; administration & dosage ; adverse effects ; therapeutic use

ObjectiveTo evaluate the clinical outcome of endoscope-assisted combined anterior and posterior procedures for grade-Ⅲ and Ⅳspondylolisthesis.MethodsFrom December 2007 to May 2010,13 patients with grade-Ⅲ and Ⅳ spondylolisthesis were treated with two bilateral decompression,percutaneous pedicle screw restoration,intervertebral bone grafting and plate fixation using microendoscopic discectomy and laparoscopy,including 6 males and 7 females with an average age of 39.8 years(range,18-58 years).Eleven cases were in grade Ⅲ spondylolisthesis and two in Ⅳ.The lesion location was as follows:2 cases were at L4,5 and 11 at L5S1.The clinical outcomes were evaluated according to Oswestry disability questionnaire,and the change of radiographic data including slipping degree,slipping angle and posterior height of intervertebral disc.ResultsThe mean follow-up time was 21 months (range,12-36 months).The mean operative time was 125 min,with a mean blood loss of 415 ml.Slipping degree decreased 56.9％ in average (from preoperative 73.3％±6.1％ to postoperative 16.4％±9.5％),slipping angle decreased 19.6°(from preoperative 27.7°±5.6° to postoperative 8.1°±8.8°),posterior height of intervertebral disc increased 7.1 mm (from preoperative 2.6 ±0.8 mm to postoperative 9.7 ±3.7 mm).The clinical outcomes of the Oswestry disability questionnaire decreased 19.5 (from preoperative 35.8±5.7 to postoperative 16.3±5.2).CT scans demonstrated that solid bony fusion could be obtained in one year after operation.Complications included dural sac tears in 1 case,and superficial incision infection in 1.The results were excellent in 4 cases,good in 8 and fair in 1.ConclusionEndoscope-assisted anterior and posterior procedures for grade-Ⅲ and Ⅳ spondylolisthesis is a reliable method,which can lead to rigid fixation and fusion,and also can achieve thorough decompression and restoration as much as possible.

Objective To evaluate hepatitis B virus large surfsce protein(LHBs) in monitoring of antiviral treatment.Methods LHBs.HBV serum markers and HBV DNA loads in 46 patients with adefovir dipivoxil(ADV) therapy were monitored for the whole course(60 weeks).Enzyme linked immunosorbent assay(ELISA),time differentiate immunofluoresence assay and real.time polymerase chain reaction(RT-PCR)were performed to detect LHBs,HBV serum markers and HBV DNA loads,respectively.And correlation analysis was also performed.Results Both LHBs and HBV DNA declined during the ADV treatment.and the correlation coefficient was 0.97.but LHBs declined after HBV DNA.There were 20 patients with HBV DNA<5×102/mL at 60th week.in which 8 were LHBs negative;in 14 recurrent patients,the HBV DNA turned to negative and became positive again,3 with negative LHBs;while in 12 patients resistant to the ADV therapy.2 were LHBs negative.Conclusion Dynamic monitoring of LHBs is useful in the evaluation of antiviral treatment.