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.

ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

ObjectiveTo investigate the value of aspartate aminotransferase-to-platelet ratio index （APRI） and platelet-albumin-bilirubin （PALBI） score in predicting the risk of esophagogastric variceal bleeding in patients with liver cirrhosis. MethodsA total of 119 patients with liver cirrhosis who were admitted to The First Affiliated Hospital of Soochow University from May 2021 and June 2022 were enrolled， and clinical data， routine blood test results， serum biochemistry， and coagulation test results were collected from all patients. According to the presence or absence of esophagogastric variceal bleeding， the patients were divided into non-bleeding group with 59 patients and bleeding group with 60 patients， and a comparative analysis was performed for the two groups. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-squared test or the Fisher’s exact test was used for comparison of categorical data between groups. The multivariate Logistic regression analysis was used to identify the independent risk factors for esophagogastric variceal bleeding in patients with liver cirrhosis and establish a nomogram predictive model. ResultsThe male patients accounted for 75.00% in the bleeding group and 40.68% in the non-bleeding group， and there was a significant difference in sex composition between the two groups （χ²=14.384， P<0.001）. Chronic hepatitis B was the main etiology in both the bleeding group and the non-bleeding group （53.33% vs 38.98%）， and there was no significant difference in composition ratio between the two groups （χ²=2.464， P=0.116）. Compared with the non-bleeding group， the bleeding group had a significantly higher activity of AT-IIIA （t=3.329， P=0.001） and significantly lower levels of PLT， TBil， Ca， TC， and TT （all P<0.05）. There were significant differences in APRI and PALBI between the two groups （χ²=6.175 and 19.532， both P<0.05）. The binary logistic regression analysis showed that APRI （odds ratio ［OR］=0.309， 95% confidence interval ［CI］： 0.109‍ ‍—‍ ‍0.881， P=0.028）， PALBI （OR=7.667， 95%CI： 2.005‍ ‍—‍ ‍29.327， P=0.003）， Ca （OR=0.001， 95%CI： 0.000‍ ‍—‍ ‍0.141， P=0.007）， TC （OR=0.469， 95%CI： 0.226‍ ‍—‍ ‍0.973， P=0.042）， and TT （OR=0.599， 95%CI： 0.433‍ ‍—‍ ‍0.830， P=0.002） were independent influencing factors for esophagogastric variceal bleeding in liver cirrhosis. A nomogram model was established based on the above factors and had an index of concordance of 0.899 and a well-fitted calibration curve. ConclusionAPRI and PALBI have a good value in predicting esophagogastric variceal bleeding in patients with liver cirrhosis， and the nomogram model established based on this study can predict the incidence rate of esophagogastric variceal bleeding in patients with liver cirrhosis.

Objective: To analyze the characteristics of small airway dysfunction in patients with occupational asthma, and explore the significance of small airway function indicators in the evaluation of occupational asthma. Methods: A total of 53 patients with occupational asthma diagnosed in our hospital from December 2008 to December 2018 were retrospectively collected in May 2020. 55 healthy people were included as the control group (NC group) and 58 bronchial asthma patients as BA group. The general information and baseline pulmonary function (FVC、FEV(1)、PEF) of the subjects were collected, the pulmonary function were reexamined and small airway function (FEF(25%)pred、FEF(50%)pred、FEF(75%)pred、MMEF(25-75%)pred) were tested at the time of diagnosis and remission. Results: There was no significant difference in pulmonary function and asthma control score (ACT) between OA group and BA group (P=0.356, 0.610, 0.364, 0.430, 0.533, 0.759, 0.426, 0.632) . The incidence of small airway dysfunction in OA group was 77.4%. The indexes of small airway function (FEF(25%)pred, FEF(50%)pred, FEF(75%)pred, MMEF(25-75%)pred) were lower than those in the NC group (P<0.001) . The small airway function indexes of mild and moderate OA patients in remission stage were improved (P=0.029, 0.182) , but the abnormal rate of small airway function was still 62.3%, and there was no significant difference compared with those at the time of diagnosis (P=0.091) . Small airway function (MMEF(25-75%)pred, FEF(50%)pred) was correlated with large airway function (FEV(1)% pred, PEF% pred) (P=0.001) . Conclusion: Small airway dysfunction often occurs and persists in patients with occupational asthma, and has a certain correlation with large airway function indexes.
Asthma, Occupational ; Humans ; Lung ; Respiratory Function Tests ; Retrospective Studies

Objective:To investigate the efficiency and safety of pneumatic retinopexy for rhegmatogenous retinal detachment (RRD).Methods:A prospective case series study. From January 2020 to December 2021, 27 eyes of 27 RRD patients in Joint Shantou International Eye Center were included. Among them, there were 10 males and 17 females; the mean age was 36.0±11.8 years old. There was recurrent retinal detachment in 4 eyes. Best corrected visual acuity (BCVA) and optical coherence tomography were performed. According to whether the retina was successfully reattached after a single intravitreal injection, the patients were divided into a single operation group and a second operation group. All eyes underwent pneumatic retinopexy, the patients received intravitreal injection of 0.3-0.5 ml 100% C 3F 8. On the next day, laser photocoagulation was performed around the retinal breaks. The mean follow-up time was 15.0±6.0 months. Outcome measures included single operation success rate, the BCVA at the last follow up and complications. The age, gender, extent of retinal detachment, number of retinal breaks, and preoperative and postoperative BCVA of patients in the single operation group and the second operation group were compared using Mann-Whiteney test or Fisher's exact test. Results:Twenty of the 27 eyes (74.1%, 20/27) had retinal reattachment after single operation, 7 of the 27 eyes (25.9%, 7/27) had retinal reattachment after the second operation. Among the 7 eyes, retinal detachment recurrence after operation, retinal detachment recurrence after tear opening, and retinal detachment recurrence with new tears occurred in 1, 4, and 2 eyes, respectively; retinas were all reattached after scleral buckling or vitrectomy. The BCVA was stable and improved in 14 and 13 eyes, respectively. Compared with the single operation group, the retinal detachment in the second operation group was wider and the BCVA before operation was worse, the differences were statistically significant ( Z=-2.842,-2.233; P<0.05). Transient intraocular pressure elevation occurred in 5 eyes; no complications such as infectious endophthalmitis, intraocular hemorrhage and lens damage occurred. Conclusion:Pneumatic retinopexy is safe and effective in the treatment of RRD.

ObjectiveTo provide a new idea for exploring the molecular genetic approach to the pathogenesis of schizophrenia via construction of microRNA-messenger RNA （miRNA-mRNA） regulatory network in schizophrenia. MethodsThe microarray datasets of GSE54578 miRNA expression profiles in peripheral blood and GSE145554 mRNA expression in the anterior cingulate in postmortem brain of schizophrenic subjects were downloaded from Gene Expression Omnibus （GEO） database since July 2021. The GEO2R was used to identify the differentially expressed miRNAs and mRNAs， screen the miRNA with target differentially expressed mRNA， and predict their potential upstream transcription factors. The overlapping genes from the mRNA targeted by the differentially expressed miRNA and the mRNA differentially expressed in GSE145554 dataset were collected. Then the biological features of hub genes were analyzed via Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis， and the protein-protein interaction （PPI） network and miRNA-mRNA regulatory network of hub genes were constructed. ResultsA total of 8 up-regulated differentially expressed miRNAs with targeted mRNA were screened out in GSE54578 datasets regarding schizophrenia， which involved in the regulation of 10 transcription factors， 247 down-regulated differentially expressed mRNAs were screened out in GSE145554 datasets， and 17 overlapping mRNAs were obtained. GO analysis showed that the target mRNAs were mainly involved in astrocyte differentiation and development. KEGG pathway enrichment analysis showed that the target mRNAs were mainly involved in Rap1 and Ras signaling pathways. PPI network analysis showed that the mRNAs （KRAS and CD28） might be key genes in schizophrenia. ConclusionThe integrated bioinformatics analysis based on GEO database can identify potential susceptibility genes in schizophrenia， and it also contributes to the construction of miRNA-mRNA regulatory network in schizophrenia.

Asthma, Occupational ; Breath Tests ; Exhalation ; Humans ; Lung ; Nitric Oxide ; ROC Curve

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.