[Risk factors for the occurrence of laryngopharyngeal reflux disease in the aged and the clinical characteristics of patients complicated with pneumonia].

Objective: To investigate the risk factors for the occurrence of laryngopharyngeal reflux disease in the aged, and to analyze the characteristics of patients with pneumonia. Methods: Patients who underwent 24-hour laryngopharyngeal pH monitoring from June 2020 to July 2022 and the positive patients of those who underwent 24-hour esophageal pH monitoring from March 2017 to July 2022 at the Second Medical Center of the PLA General Hospital were enrolled retrospectively. Positive results of 24-hour laryngopharyngeal reflux monitoring were in the laryngopharyngeal reflux group, and the negative results were in the non-laryngopharyngeal reflux group. Patients with pneumonia and simple gastroesophageal reflux disease were in the esophageal reflux pneumonia group, and patients with pneumonia and simple laryngopharyngeal reflux disease were in the laryngopharyngeal reflux pneumonia group. Patients' basic data, co-morbidities, drug use and relevant examination and test results were collected. Multivariate logistic regression analysis was used to analyze the risk factors of laryngopharyngeal reflux disease in the aged and its relationship with pneumonia. Results: A total of 80 patients with 24-hour laryngopharyngeal pH monitoring were enrolled finally, including 34 cases, all male, aged (73±12) years, in the laryngopharyngeal reflux group, and 46 cases [44 males, 2 females, aged (78±11) years] in the non-laryngopharyngeal reflux group. Multivariate logistic regression analysis showed that the risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years (OR=13.07, 95%CI: 2.53-67.68), body mass index (BMI) (OR=1.37, each additional 1 kg/m2, 95%CI: 1.03-1.83), use of antipsychotic drugs (OR=8.00, 95%CI: 1.40-45.73) and calcium channel blockers (OR=5.27, 95%CI: 1.13-24.53) (all P<0.05). The protective factors of the laryngopharyngeal reflux disease in the aged included antacids (OR=0.19, 95%CI: 0.04-0.90, P=0.035). The incidence of pneumonia was higher in the laryngopharyngeal reflux group compared with the non-laryngopharyngeal reflux group [44.1% (15/34) vs 21.7% (10/46), P=0.033]. The esophageal reflux pneumonia group included 32 cases [31 males and 1 females, aged (84±12) years]. The laryngopharyngeal reflux pneumonia group included 15 cases [ 15 males, aged (79±11) years]. Compared to the patients in the laryngopharyngeal reflux pneumonia group, the patients in the esophageal reflux pneumonia group had a longer course of antibiotics [(27.7±27.0) vs (14.6±13.9) days, P=0.034], a higher frequency of seizure frequency [(4.3±3.0) vs (1.8±1.5) times/year, P<0.001] and a higher maximal body temperature [(38.2±0.9) vs (37.6±1.1) ℃, P=0.037]. Conclusions: The risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years, higher BMI, use of antipsychotic drugs and calcium channel blockers. The incidence of pneumonia in laryngopharyngeal reflux disease is higher, but the condition of pneumonia is milder.

[Application of omics in the diagnosis of metabolic dysfunction-associated fatty liver disease].

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, and the risk of all-cause and liver-related mortality significantly increases with the degree of fibrosis. Early diagnosis of MAFLD and its degree of liver fibrosis are of great significance, so it is particularly important to find an accurate and simple, non-invasive diagnostic method. In recent years, high-throughput omics technology has developed rapidly and played an important role in the non-invasive diagnosis and prediction of fibrosis degree in MAFLD. This article summarizes the application progress of genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, radiomics, and the combination of multi-omics for the diagnosis of MAFLD disease.

[Study on warfarin medication checklist for improving patient compliance].

This study explored whether clinical pharmacists can improve patients' medication compliance with the use of warfarin medication checklist and the correlation between them. A total of 147 inpatients discharged from Shanghai Tongren Hospital with warfarin from July 2018 to September 2019 were randomly divided into the control group and the intervention group by random number table, including 75 in the control group and 72 in the intervention group. There were no statistically significant differences in gender, age, marital status, drinking history, smoking history, department distribution, type of thromboembolic disease, comorbidity and combined medication between the two groups (P>0.05). The control group received routine warfarin medication education at discharge, while the intervention group received clinical pharmacist's assessment of bleeding risk and targeted medication education using warfarin medication checklist at discharge. The monitoring time and value of the international normalized ratio (INR) between the two groups during hospitalization and within 6 months after discharge were recorded, as well as warfarin-related adverse events. The Morisky Medication Adherence Scale was used to evaluate the medication compliance of patients in the two groups. Spearman correlation analysis was used to study the relationship between warfarin compliance and variables in the warfarin medication checklist. The intervention group had better follow-up regularity than the control group (χ²=34.3, P<0.001), and the medication compliance in the intervention group was better than that in the control group (χ²=38.6, P<0.001). There were significant correlations between warfarin compliance and duration of warfarin therapy (R=-0.275, P=0.027), number of comorbidities (R=-0.335, P=0.004), bleeding risk (R=-0.433, P<0.001). In conclusion, using warfarin medication checklist can improve patients' medication compliance. Patients' medication compliance was significantly negatively correlated with duration of warfarin therapy, number of comorbidities and bleeding risk. Clinical pharmaceutical care can improve the medication compliance of patients with warfarin, so as to improve the medication results, which may be helpful for the drug treatment of patients with chronic diseases.

[Retrospectively analysis of characteristics and risk factors of immune treatment-related hepatic adverse events in malignant tumor].

Objective: To explore the clinical features and risk factors of hepatic injury due to immune checkpoint inhibitors (CPI) therapy in malignant tumor. Methods: Data of 112 patients (64 men and 48 women) who received CPI between January 2016 and March 2019 in Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen Hospital, and Huazhong University of Science and Techology Union Shenzhen Hospital were retrospectively collected. The median age of these patients was 60 years. Results: Hepatic adverse events were observed in 30 patients out of 112 patients (26.8%). Among them, the incidence of grade 3-5 hepatic adverse events were 7.14% (8/112). The median time of hepatic adverse event occurrence was 3 weeks (2-30) after undergoing therapy. The results of univariate and multivariate analyses showed that liver cancer was attributed to the CPI induced hepatitis (P<0.05). Patients with severe hepatic injury got almost complete resolution after receiving methlprednisolone for 4 to 6 weeks. Conclusion: Live cancer is the risk factor of CPI-related hepatic adverse events.

[Analysis of drug resistance pattern and genes of Salmonella.spp isolated from human infections in Anhui Province].

Objective: To investigate the drug resistance pattern and drug resistance genotypes of Salmonella. spp isolated from fecal specimens and anal swabs of diarrhea cases in Anhui Province. Methods: The 149 strains of Salmonella.spp isolated from feces and anal swabs of diarrhea cases in Anhui Province from April to October 2017 were selected. The serotypes of Salmonella.spp were identified by slide agglutination. The susceptibility of all strains to 14 antibiotics were determined by micro-broth dilution method. Sixty of the cephalosporin-resistant antibiotics were selected. The ß-lactamase encoding genes bla(TEM), bla(SHV), bla(OXA-1), bla(OXA-2), bla(PER), bla(CMY), bla(CTX-M), and colistin resistance genes mcr-1 and mcr-2 were performed using the multi-PCR method. Results: Of the 149 diarrhea cases, the median (P(25), P(75)) of the age was 5.0 (1.1, 38.5). The 92 of them were male and 54.4% were children. Of the 149 strains of Salmonella.spp, 105 strains had different degrees of resistance to 13 antibiotics other than imipenem. The resistance rate of ampicillin was 55.0% (82/149), which was the highest. 53.0% strains (79 strains) were multidrug resistant, main of which were Salmonella typhimurium and Salmonella enteritidis. A total of 53 resistance patterns were detected, and 10 strains were resistant to ampicillin-ampicillin/sulbactam-tetracycline-chloramphenicol-cefazolin-trimethoprim/sulfamethoxazole, which was the most common resistance pattern. Among the 60 cephalosporin resistant strains, 45 strains carried bla(TEM-1), 6 of which also carried bla(CTX-M-14) and 3 of which also carried bla(CTX-M-65). All the 32 strains carried only bla(TEM-1) show resistance to ampicillin and 31 of them show resistance to cefazolin. There were 2 strains showing negative results of gene detection. mcr-1 was detected in a multidrug resistant strain. Conclusion: The resistance of Salmonella.spp to ampicillin shows a serious situation in this region, and there were a number of multidrug resistant strains. The bla(TEM-1) was the major drug resistance gene detected in this research. Detection of the mcr-1 suggests the emergence of surveillance to colistin resistance of Salmonella.spp in this area.

Drug-resistance reversal in colorectal cancer cells by destruction of flotillins, the key lipid rafts proteins.

Multi-drug resistance (MDR) of tumor cells attenuates the efficacy of anticancer drugs and has become the main reason for chemotherapy failure. It is indispensable to establish an effective way to reverse multi-drug resistance. Our previous work has shown that down-regulation of the ERK/MAPK signaling pathway activity can reverse the drug-resistance of resistant cells. Further-more, the effect of signal transduction is strongly associated with lipid rafts. The drug-resistance is reversed successfully after lipid rafts are destroyed by heptakis(2, 6-di-O-methyl)-ß-cyclodextrin (MßCD). However, the reversal of the drug-resistance is not associated with down-regulation of the expression of ERK1/2. Cell membrane permeability may increase when lipid rafts are destroyed by MßCD, causing the reversal of drug-resistance due to an increase in accumulation of the drugs in the cytoplasm. To minimize the influence of MßCD on the cell membrane structure, we selected flotillin, a marker protein of lipid rafts, as the target molecule, to further investigate the mechanism of changes in drug resistance after destruction of the lipid rafts. The effect of flotillin on the reversal of the drug resistance was examined using an RNA interference (RNAi) in a retrovirus system in human drug-resistant strains of colorectal cancer cell line HCT-15. The results demonstrate that flotillin-1 downregulation by RNAi (Flot1-RNAi) reduced the drug resistance, caused cell cycle arrest and decreased the expression of ERK1/2; however, apoptosis was not significantly affected. Knockdown of flotillin-2 by RNAi (Flot2-RNAi) had effects similar to those of Flot1-RNAi except that the effects on expression of ERK1/2 and apoptosis were different. Screening of multiple pathways indicated that the PI3K/Akt signaling pathway was closely related. This experiment demonstrates the association between PI3K and drug resistance through the activation of PI3K and suggests that PI3K may play a key role during the development of resistance in CRC. The results reveal that the levels of IRS-1 and PI3K proteins in the Flot1-RNAi and Flot2-RNAi groups were significantly down-regulated. Knockdown of flotillins by RNAi reduced the resistance of HCT-15/ADM cells; the results investigations of the Akt pathway indicate a decrease in resistance after lipid raft destruction. These data confirm that knockdown of flotillin reduces the resistance of HCT-15/ADM cells, and the mechanism may be relevant to the PI3K/Akt pathway. Additionally, flotillin may be used as a potential target for chemotherapy in the treatment of colorectal cancer.

Cutaneous tuberculosis in China - A multicentre retrospective study of cases diagnosed between 1957 and 2013.

BACKGROUND: China has one of the largest populations with tuberculosis worldwide. Cutaneous tuberculosis (CTB) is a rare manifestation of mycobacterial infection. Although CTB is well described, it is important to periodically revisit the prevailing clinical and epidemiological features in most populated countries such as China, India, and Indonesia, where tuberculosis is still a major health problem. OBJECTIVE: This retrospective study aimed to re-evaluate the CTB cases in China in the past 50 years to obtain a comprehensive insight into this multiplex entity. METHODS: Cases of diagnosed CTB with confirmed histology from four large medical centres in central China between 1957 and 2013 were collected and analysed, including demographic data, clinical manifestations and pathological findings. RESULTS: Of the 1194 cases enrolled, there were 666 (55.78%) and 528 cases (44.22%) of true CTB and tuberculids, respectively. Erythema induratum of Bazin (EIB) was the most common CTB (35.8%), followed by lupus vulgaris (LV, 32.7%), tuberculosis verrucosa cutis (18.9%), papulonecrotic tuberculid (8.0%), scrofuloderma (2.8%), tuberculosis cutis ulcerosa (1.3%), penile tuberculids (0.4%), and lichen scrofulosorum (0.1%). EIB was the predominant tuberculid (80.87%), while LV the predominant true CTB (58.7%). The number of diagnosed CTB showed a decreasing trend in the 1960s and 1970s, then increased again, and peaked in the 1990s. CONCLUSIONS: Cutaneous tuberculosis is still a common problem in China. Chronologic changes in CTB cases reported in China over the past 50 years may reflect the prevalence transition of overall tuberculosis. CTB has diverse clinical presentations, and each subtype is characterized by specific gender predilection, duration, age, clinic and pathological findings.

[Curative effects and influenced factors of primary chemotherapy with single-agent methotrexate on low-risk gestational trophoblastic neoplasia].

Objective: To evaluate the efficacy of primary chemotherapy with single-agent methotrexate (MTX) for low-risk gestational trophoblastic neoplasia and to analysis the influenced factors. Methods: We retrospectively reviewed 259 cases with low-risk gestational trophoblastic neoplasia whose primary chemotherapies were MTX 0.4 mg·kg(-1) (maximum 25 mg) daily for 5 days every other week. Patients' data between January 2001 and June 2015 was collected and the relationships of different factors to outcomes of chemotherapy were also evaluated. Results: 183 of the 259 patients (70.66%, 183/259) achieved complete primary remission and all patients achieved complete remission after salvage chemotherapy. Univariate analysis showed that FIGO score, serum level of HCG before treatment and interval months from previous pregnancy were significantly associated with outcome of chemotherapy (P=0.001, 0.018, 0.014 respectively). Logistic regression analysis showed that the FIGO score (OR=4.094) and antecedent pregnancy (OR=0.268) were two independent factors predictive for the outcome of chemotherapy. Conclusions: Primary chemotherapy with single-agent MTX may still be one of the options for patients with low risk GTN. The FIGO score and antecedent pregnancy are two independent risk factors of outcome of single-agent MTX chemotherapy.

Application of ultrasound technology in the study of ischemic postconditioning to protect testes from ischemia-reperfusion injury.

This study was designed to investigate the application of ultrasound technology in the study of ischemic postconditioning to protect testes from ischemia-reperfusion injury. Seventy-two big white rabbits were divided into mild ischemic groups (Group A: A0, A1, A2, A3), moderate ischemic groups (Group B: B0, B1, B2, B3) under ultrasound monitor, and control group (N = 8). Groups A0 and B0 received direct perfusion, while the other groups received a different short time filling/stopped filling treatment (15 s/15 s, 30 s/30 s, or 45 s/45 s) three times before complete perfusion. Each group received contrast-enhanced ultrasound before complete filling. At 3 days after perfusion, the testicular tissue was removed for biopsy. The parameters of testicular contrast in pre-reperfusion groups A and B differed significantly from those of their corresponding control groups (P < 0.05). The changes in testis-related pathological indicators in groups A1 and A2 were more significant than those of group A0 (P < 0.05), and changes in group B2 were more obvious than those of group B0 (P < 0.05). There were no statistically significant differences in the comparison of other indicators between the corresponding groups (P > 0.05). Ultrasound technology can help build different degree models of ischemic testes and predict the protective effect of post-ischemic treatment.

Development of a real-time impedance matching system for ion cyclotron resonance heating in experimental advanced superconducting tokamak.

To achieve stable operation of an ion cyclotron resonance heating (ICRH) system in the Experimental Advanced Superconducting Tokamak (EAST), a real-time impedance matching system needs to be established to respond to antenna load variation during long pulse discharges. A new impedance matching method based on capacitors was proposed in this study. By considering the reflected voltage of the transmission line as the feedback parameter, the real-time impedance-matching system can quickly control the motors based on a programmable logic controller to determine the minimum reflection voltage. A real-time impedance matching system was successfully used on the test platform in the laboratory and on the ICRH system in EAST. A significant result is that we can match the variable impedance within 1 s by suitably adjusting the motor controller to ensure high-power and long-pulse operation of the ICRH system to satisfy the requirements of the EAST experiment.

Risk factors for early-onset ventilator-associated pneumonia in aneurysmal subarachnoid hemorrhage patients.

This study aimed to investigate the risk factors related to ventilator-acquired pneumonia (VAP) in aneurysmal subarachnoid hemorrhage (SAH) patients. From January 2011 to December 2015, a single-center retrospective study including 200 SAH patients requiring mechanical ventilation (MV) ≥48 h was performed. The clinical data of these patients were collected and analyzed. The age range of the patients were 41-63 and 72 (36%) were male. The Glasgow coma scale score range was 5-15 and the Simplified Acute Physiology Score II range was 31-52. One hundred and forty-eight (74%) patients had a World Federation of Neurosurgeons (WNFS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 168 (84%) patients and 94 (47%) patients presented VAP. Male gender (OR=2.25, 95%CI=1.15-4.45), use of mannitol (OR=3.02, 95%CI=1.53-5.94) and enteral feeding above 20 kcal·kg-1·day-1 (OR=2.90, 95%CI=1.26-6.67) after day 7 were independent factors for VAP. Patients with early-onset VAP had a longer duration of sedation (P=0.03), MV (P=0.001) and ICU length of stay (P=0.003) and a worse Glasgow Outcome Scale score (P<0.001), but did not have a higher death rate.

The first epidemic of dengue hemorrhagic fever in the People's Republic of China.

The first epidemic of dengue in China associated with significant severe and fatal hemorrhagic disease which met the World Health Organization case definition occurred on Hainan Island in 1985-1986. The epidemic began in Zhan County in September 1985, spread throughout the coastal areas, and ultimately involved 13 counties and cities of the island in 1986. The mosquito vector was Aedes aegypti. The morbidity associated with dengue infection on Hainan Island was 1,913 per 100,000 residents, with a case fatality rate of 0.25%. Severe disease was more prevalent in the 10-29-year-old age group. Principal clinical features in laboratory-confirmed cases were fever, osteoarthralgia, hemorrhage and/or shock, and thrombocytopenia. Complications such as acute intravascular hemolysis, diffuse intravascular coagulation, hemoconcentration, pleural effusion, altered mentality, and pneumonia were also observed. One hundred twenty-five isolates of dengue 2 virus were recovered from acute-phase serum samples from 278 patients, and 5 strains of this same virus serotype were isolated from 5 pools of adult Ae. aegypti.

Comparative study on the metabolism of optical gossypol in rats.

The comparative metabolism of (+)- and (-)-gossypol in rats was studied. After oral administration of the drugs to rats, the half-lives of (+)- and (-)-gossypol in the gastrointestinal tract were found to be 18.4 h and 13.5 h, respectively. The tissue distribution of (+)-gossypol was very similar to that of (-)-gossypol. After oral administration, high drug levels were found in the liver while moderate concentrations were present in the spleen, lungs, blood, heart and kidneys. The drug levels in the testes and fat were rather low. The excretion rates of the (+)- and (-)-gossypol were quite similar. Most of the ingested drug was excreted in the feces, while only a small fraction was eliminated in the urine. After i.v. injection of the drugs to rats, the half-lives of free (+)- and (-)-gossypol were found to be 7.80 h and 3.96 h, respectively. The clearance rates of the two optical isomers were 7.81 and 29.36 ml/h, respectively.

A survey of epidemiology of Gnathostoma hispidum and experimental studies of its larvae in animals.

The present study is concerned with a survey of the epidemiology and infectivity of Gnathostoma hispidum larvae in animals. A total or 3,478 pigs were examined in Hongze-Lake, Jiangsu; Po-Lake, Anhui; and Jiujiang, in Jiangxi Province. The infection rate of G. hispidum in pigs was 14.9%. The prevalence in pigs in the lake districts (26.4%) was considerably higher than in the mountainous districts (5.1%). The results of field surveys and experimental studies revealed that in China, 38 animal species served as the first and the second intermediate hosts and paratenic hosts of G. hispidum. Among them, 23 species (6 cyclops, 13 fish, 2 frogs and one each of snake and bird) were similar to the hosts of G. spinigerum. Carnivorous fish, frogs and rodents are an important infection source for gnathostomiasis. Experiments demonstrated that Macaca mulatta was successfully infected with the early 3rd-stage larvae from cyclops or the advanced 3rd-stage larvae from fish. The domestic cat and white rat were experimentally infected by skin penetration by advanced 3rd-stage larvae of G. hispidum obtained from fish; the results of the test were all positive. The survey of epidemiology and biology of G. hispidum and G. spinigerum were quite similar, so the authors consider that humans may be infected by G. hispidum.

[Column switching HPLC method for determination of in vivo release of norethindrone-alpha, beta-poly (3-hydroxypropyl)-DL-asparamide conjugate].

An HPLC method for the determination of in vivo release of norethindrone-alpha, beta-poly (3-hydroxypropyl)-DL-asparamide (NET-PHPA) conjugate was established using column switching technique. The sample prepurification could be omitted. It was extracted by a precolumn (ODS, 9-11 microns) and the analytical column was packed with ODS (15 cm x 4 mm ID. Shimpac CLC). The mobile phases were water and methanol--water (7:3) respectively. The experiment showed that the recovery from serum was 82.6%, the RSD within day was 1.3-1.8% and that in day-to-day was 0.7-5.6% (n = 4).

Aspirin may modify tumor microenvironment via antiplatelet effect.

High-quality evidence suggests that aspirin is a promising agent for cancer prevention and treatment. Direct inhibition of cyclooxygenase-2 (COX-2) pathway is generally thought to be the main mechanism by which aspirin inhibits cancer development. However, either pharmacological properties of aspirin or recent results of epidemiologic studies do not support that mechanism. To address this inconsistency, we hypothesize that antiplatelet effect of aspirin via inhibition of COX-1 may be one of potential mechanisms to inhibit carcinogenesis. Aberrant platelet activation will lead to promote hostility of tumor microenvironment by releasing an abundant array of angiogenesis regulators. Given the outstanding ability of antiplatelet, aspirin may restore balance of pro- and anti-angiogenic factors released from platelet to "normalize" tumor vasculature and shape tumor microenvironment to some extent, which will not only diminish tumor aggressiveness and progression, but also enhance the sensitivity to therapeutic treatment. Thus, targeting the platelet activation leading to alter tumor microenvironment may provide a novel way to tumor therapy.