OBJECTIVE To analyze the characteristics of severe cutaneous adverse reactions （SCARs） induced by oral anticoagulants （OACs）， and provide a reference for clinical safety of drug use. METHODS Case reports of SCARs caused by OACs （warfarin， apixaban， rivaroxaban， edoxaban， dabigatran etexilate） were retrieved from PubMed， Embase， CNKI， Wanfang Data， VIP and other databases with search terms as “oral anticoagulants”“factor Ⅹa inhibitor”“direct thrombin inhibitor” and their Chinese equivalents. A descriptive statistical analysis was performed. RESULTS A total of 11 articles were included， involving 11 patients in total， among whom there were 5 males （45.5%） and 6 females （54.5%）， with an average age of （59.6±21.5） years. The primary underlying diseases were mainly atrial fibrillation， pulmonary embolism， joint replacement and valve replacement. The OACs involved included warfarin in 3 cases， rivaroxaban in 4 cases， apixaban in 2 cases， and dabigatran etexilate in 2 cases. SCARs occurred from 10 hours to 42 days after treatment， and 7 cases （63.6%） within 10 to 28 days. Among 11 patients， 5 cases were diagnosed as drug reaction with eosinophilia and systemic symptoms， 4 cases were diagnosed as Stevens-Johnson syndrome or toxic epidermal necrolysis， and 2 cases were diagnosed as acute generalized exanthematous pustulosis. The clinical manifestations mainly included rash， fever and mucosal damage， etc. Except for 1 patient who died of sepsis and diffuse intravascular coagulation， the rest of the patients improved or recovered after withdrawal and treatment with glucocorticoids. CONCLUSIONS SCARs are rare but serious adverse reactions caused by OACs， typically occurring 10 to 28 days after medication. Once SCARs are suspected to be caused by OACs， the medication should be discontinued immediately， and a treatment plan should be formulated based on the type of SCARs to ensure the safety of patients’ drug use.

Objective:To explore the efficacy and safety of endovascular intervention combined with preoperative laparoscopic exploration in the treatment of patients with acute mesenteric artery ischemia.Methods:This was a prospective cohort study (NCT04686981). The study enrolled 31 patients with acute mesenteric artery ischemia from Oct 1, 2020 to Oct 1, 2022. Among them, 26 patients (84%) were male, with a mean age of (67±13) years and a mean time to onset of (21±8) hours. All patients underwent laparoscopic exploration in the hybrid operating room. If the presence of intestinal necrosis or suspected necrosis was clearly determined, the patient would undergo open surgery (mesenteric artery embolization, intestinal resection and intestinal double stoma) as the treatment by gastrointestinal surgeon. If intestinal necrosis or suspected necrosis was not found by laparoscopy, the patient would undergo endovascular intervention by vascular surgeon. The primary observational endpoints of this study were the proportion of patients who were not dependent on total parenteral nutrition and all-cause mortality within 30 days after operation. The secondary observational endpoints were the rate of mesenteric vascular patency within 30 days and the proportion of interventions that were converted to open surgery.Results:Six patients underwent open surgery and 25 patients underwent endovascular intervention, including 13 cases of thrombus reduction alone, 3 cases of stent implantation during the same period after reduction, and 9 cases of stent implantation alone. Twenty-four patients (77%) were completely weaned from the TPN within 30 days after the procedure, and all-cause mortality was observed in 3 cases (9.7%). The patency rate of the mesenteric artery within 30 days after the procedure was 82.1%. The rate of conversion to open surgery after intervention was 16%.Conclusions:Endovascular intervention combined with preoperative laparoscopic exploration can clarify intestinal ischemia in acute mesenteric patients as early as possible, and individualized treatment strategies for each patient by multidisciplinary care team can potentially improve the prognosis of such patients.

Objective:To explore the clinical application value of salivary pepsin test (Peptest) in the diagnosis of gastroesophageal reflux disease (GERD).Methods:From April to October 2022, at the Department of Gastroenterology of the First Affiliated Hospital of Nanjing Medical University, a total of 81 patients with typical reflux and (or) heartburn symptoms for more than 1 month, who were diagnosed with GERD and completed 24-hour esophageal pH impedance monitoring (24 h MII-pH) and high-resolution esophageal manometry were enrolled. Salivary samples were collected after lunch, at the onset of symptoms, and at random time point on the day of intubation, and all patients received standard dose of proton pump inhibitor (PPI) for 2 weeks. The 24 h MII-pH results were taken as the gold standard for diagnosing GERD. The optimal time point of Peptest and the diagnostic value of combination of Peptest and PPI test in GERD diagnosis were analyzed. The 24 h MII-pH negative patients were further divided into Peptest-positive group and Peptest-negative group. The heartbrun scores, gastroesophageal reflux disease questionnaire (GERD-Q), reflux characteristics, and esophageal motility between the 2 groups were compared and to investigate the differential diagnostic value of Peptest in 24 h MII-pH negative patients. Chi-square test and non-parametric test were used for statistical analysis.Results:The results of 24 h MII-pH indicated that 21 patients (25.9%, 21/81) were diagnosed GERD and 60 patients were negative for 24 h MII-pH. The onset of symptoms was the optimal time point for Peptest, with a sensitivity of 80.9%, a specificity of 50.0%, and an accuracy of 58.0%. The specificity and accuracy of Peptest at the onset of symptoms combined with PPI test in GERD diagnosis were higher than those of Peptest at the onset of symptoms alone (75.0% vs. 50.0%, 74.1% vs. 58.0%), and the differences were statistically significant ( χ2=8.00 and 4.65, P=0.005 and 0.031). Among 60 cases of 24 h MII-pH negative patients, 30 were positive for Peptest at the onset of symptoms and 30 were negative for Peptest at the onset of symptoms. The heartburn scores and GERD-Q scores of Peptest-positive group were both higher than those of Peptest-negative group (3.0 (2.0, 3.0) vs. 1.0 (0.0, 2.3), 12.0 (9.8, 13.0) vs. 9.0 (6.0, 11.0) ); the clearance time of acid reflux of Peptest-positive group was longer than that of Peptest-negative group (57.0 s (22.3 s, 88.0 s) vs. 18.3 s (9.6 s, 32.1 s) ); the lower esophageal sphincter resting pressure and integrated relaxation pressure were lower than those of Peptest-negative group (10.40 mmHg (5.75 mmHg, 18.95 mmHg) vs. 21.45 mmHg (10.65 mmHg, 31.70 mmHg), 3.90 mmHg (2.05 mmHg, 5.35 mmHg) vs. 4.90 mmHg (3.76 mmHg, 8.25 mmHg); 1 mmHg=0.133 kPa); the distal mean nocturnal baseline impedance, the distal contractile integral and esophagogastric junction contractile integral were all lower than those of Peptest-negative group ( 1 783 Ω (1 660 Ω, 2 157 Ω) vs. 2 300 Ω(1 805 Ω, 2 370 Ω), 1 416 mmHg·s·cm (919 mmHg·s·cm, 2 176 mmHg·s·cm) vs. 1 858 mmHg·s·cm (1 395 mmHg·s·cm, 2 880 mmHg·s·cm), 27.7 mmHg·cm (19.8 mmHg·cm, 39.5 mmHg·cm) vs. 52.6 mmHg·cm (27.7 mmHg·cm, 74.6 mmHg·cm) ), and the differences were statistically significant ( Z=-4.00, -3.53, -3.31, -2.34, -2.13, -2.75, -2.14 and -2.43; P<0.001, <0.001, =0.001, =0.019, =0.033, =0.006, =0.032 and =0.015). Conclusions:Peptest may be better at diagnosing GERD at the onset of symptoms compared to postprandial, random time points, and the accuracy of diagnosing GERD further improves when combined with PPI test. Peptest at the onset of symptoms may have differential diagnostic value for GERD patients in 24 h MII-pH negative patients.

Objective:To explore the efficacy and influencing factors of linaclotide in patients with functional defecation disorder (FDD).Methods:From June 1, 2021 to February 28, 2023, at the First Affiliated Hospital of Nanjing Medical University, 160 patients with FDD were enrolled and randomly divided into linaclotide group and polyethylene glycol group by using a random number table method, with 80 cases in each group, and the treatment course both was 4 weeks. The efficacy, weekly complete spontaneous bowel movement (CSBM), patient assessment of constipation symptom (PAC-SYM), numerical rating scale (NRS), Zung′s self-rating anxiety scale (SAS) and Zung′s self-rating depression scale (SDS) before and after treatment of linaclotide group and polyethyetylene glycol group were recorded and compared. Multivariate logistic regression analysis was performed to analyze the factors affected linaclotide in the treatment of FDD (including anorectal manometry). Receiver operating characteristic curve (ROC) was used to analyze the predictive value of risk factors on the efficacy of linaclotide in FDD. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:After treatment, the weekly CSBM frequencies of linaclotide group and polyethylene glycol group were both higher than those before treatment in the same group (3.20±2.03 vs. 2.44±2.09, 3.10±2.26 vs. 2.58±2.06), and the differences were statistically significant ( t=-4.85 and -5.91, both P<0.001). After treatment, PAC-SYM score of stool shape, rectal symptom, abdominal symptom and total score, NRS score, SAS score and SDS score of linaclotide group and polyethylene glycol group were all lower than those before treatment in the same group (1.41±0.96 vs. 1.89±1.13, 0.95±0.49 vs. 1.14±0.46, 0.69±0.57 vs. 1.00±0.58, 0.96±0.43 vs. 1.23±0.40, 1.54±1.11 vs. 2.48±1.24, 43.54±6.26 vs. 45.13±7.30, 42.10±7.95 vs. 43.78±9.15 and 1.36±1.09 vs. 1.88±1.17, 0.83±0.40 vs. 1.10±0.45, 0.81±0.60 vs. 1.01±0.69, 0.91±0.42 vs. 1.21±0.41, 1.90±1.17 vs. 2.23±1.27, 43.55±7.72 vs. 44.61±8.51, 40.00±6.71 vs. 41.18±7.50), and the differences were statistically significant ( t=7.08, 7.73, 7.15, 9.26, 7.66, 7.96, 8.46, 7.26, 7.16, 5.78, 8.37, 6.17, 4.67 and 7.13, all P< 0.001). After treatment, the NRS score of linaclotide group was lower than that of polyethylene glycol group, and the difference was statistically significant ( t=-2.01, P=0.046). The total effective rate of linaclotide group was higher than that of polyethylene glycol group (77.5%, 62/80 vs. 62.5%, 50/80), and the difference was statistically significant ( χ2=4.29, P=0.038). The results of multivariate logistic regression analysis showed that the threshold of initial sensory volume and maximum tolerable volume were independent risk factors for linaclotide treatment of FDD ( OR=0.965, 95% confidence interval 0.936 to 0.995, P=0.022; OR=0.980, 95% confidence interval 0.962 to 0.999, P=0.041). The results of ROC analysis showed that the efficacy of linaclotide was poor in FDD patients with the threshold of initial sensory volume >67.5 mL or maximum tolerable volume > 117.5 mL. The combined predictive value of initial sensory volume and maximum tolerable volume threshold was higher than that of individual prediction, with an area under the curve of 0.722, sensitivity of 79.0% and specificity of 55.6%. Conclusions:Linaclotide can improve CSBM, constipation symptoms, abdominal pain and psychological status of FDD patients. The initial sensory volume threshold and maximum tolerable volume threshold are independent risk factors of the efficacy of linaclotide in FDD treatment and have certain predictive value in efficacy.

Objective:To integrate the best evidence of non-drug intervention of urinary incontinence in elderly women and to formulate practical recommendations.Methods:In this systematic review study, using “elderly woman”,“urinary incontinence”,“bladder training”,“pelvic floor muscle training”,“enuresis”,“leakage of urine” as the key words, the 6S evidence resource pyramid model was used to search in British Medical Journal best practice, Uptodate, World Health Organization, Guidelines International Network, National Institute for Health and Care Excellence, Chinese Medical Association, Scottish Intercollegiate Guideline Network, Registered Nurses Association of Ontario, Cochrane Library, The Joanna Briggs Institute (JBI), New Zealand Guidelines Group, Polish Society of Gynecologists and Obstetricians, PubMed, Embase, Medline, Web of Science, SinoMed, China National Knowledge Infrastructure, WanFang Data, etc. The evidence retrieved included evidence-based knowledge base resources, clinical practice guidelines, expert consensus, systematic review, etc. Data were retrieved from January 1, 2017 to May 1, 2022, and collated from May 2, 2022 to May 25, 2022. Two researchers independently evaluated the quality of literature and extracted data using the AGREE Ⅱ and JBI evidence-based health care center assessment tools. The JBI evidence-based health care center′s evidence pre-rating system and evidence recommendation rating system were applied to rank the evidence; and under the guidance of the evidence structure of JBI, the strength of evidence recommendation was determined and the best evidence was extracted and summarized in combination with the study group discussion and expert opinion.Results:A total of 9 articles were retrieved, including 7 guidelines and 2 systematic reviews; and 6 guidelines were classified as Grade A and 1 as grade B; both 2 systematic reviews were rated as Grade A; 84% (27/32) of the items were evaluated as “Yes”. Evidence were summarized as 34 pieces of best evidence from 6 dimensions, including “overall recommendation, evaluation of type and degree of urinary incontinence, lifestyle change, behavioral therapy, prevention of precipitating factors, intervention in special population”; the flow chart of screening, evaluation, special symptoms, life style and behavior therapy was combed, and the practical suggestions were formed.Conclusions:The overall quality of the literature on non-drug intervention of urinary incontinence in elderly women is high, and the level of evidence is high. Early identification of urinary incontinence types and assessment of disease severity, lifestyle changes, avoidance of predisposing factors and behavioral therapy are the key to non-drug treatment of urinary incontinence in those patients.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

With the escalation of plastic bans and restrictions, bio-based plastics, represented by polylactic acid (PLA), have become a major alternative to traditional plastics in the current market and are unanimously regarded as having potential for development. However, there are still several misconceptions about bio-based plastics, whose complete degradation requires specific composting conditions. Bio-based plastics might be slow to degrade when it is released into the natural environment. They might also be harmful to humans, biodiversity and ecosystem function as traditional petroleum-based plastics do. In recent years, with the increasing production capacity and market size of PLA plastics in China, there is an urgent need to investigate and further strengthen the management of the life cycle of PLA and other bio-based plastics. In particular, the in-situ biodegradability and recycling of hard-to-recycle bio-based plastics in the ecological environment should be focused. This review introduces the characteristics, synthesis and commercialization of PLA plastics, summarizes the current research progress of microbial and enzymatic degradation of PLA plastics, and discusses their biodegradation mechanisms. Moreover, two bio-disposal methods against PLA plastic waste, including microbial in-situ treatment and enzymatic closed-loop recycling, are proposed. At last, the prospects and trends for the development of PLA plastics are presented.
Humans ; Ecosystem ; Biodegradable Plastics ; Polyesters ; Biodegradation, Environmental

Objective: The etiology of schizophrenia is unknown and is associated with abnormal spontaneous brain activity. There are no consistent results regarding the change in spontaneous brain activity of people with schizophrenia. In this study, we determined the specific changes in the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF) and regional homogeneity (ReHo) in patients with drug-naïve first-episode schizophrenia (Dn-FES). Methods: A comprehensive search of databases such as PubMed, Web of Science, and Embase was conducted to find articles on resting-state functional magnetic resonance imaging using ALFF/fALFF and ReHo in schizophrenia patients compared to healthy controls (HCs) and then, anatomical/activation likelihood estimation was performed. Results: Eighteen eligible studies were included in this meta-analysis. Compared to the spontaneous brain activity of HCs, we found changes in spontaneous brain activity in Dn-FES based on these two methods, mainly including the frontal lobe, putamen, lateral globus pallidus, insula, cerebellum, and posterior cingulate cortex. Conclusion We found that widespread abnormalities of spontaneous brain activity occur in the early stages of the onset of schizophrenia and may provide a reference for the early intervention of schizophrenia.

Background: The laryngopharyngeal symptoms of gastroesophageal reflux disease (GERD) include hoarseness, foreign body sensation, chronic cough, dysphagia, etc. Its pathogenic mechanisms and reflux characteristics may be different from those of GERD patients simply with typical esophageal symptoms. Aims: To explore the clinical characteristics of GERD patients complicated with laryngopharyngeal symptoms. Methods: Fifty-nine patients having a gastroesophageal reflux disease questionnaire (GerdQ) score ≥8 and abnormal reflux identified by 24 h esophageal impedance-pH monitoring were selected from the outpatients at the First Affiliated Hospital of Nanjing Medical University from January 2019 to December 2021. Twenty-nine cases simply with typical esophageal symptoms were allocated into typical symptom group, and 30 cases complicated with laryngopharyngeal symptoms were allocated into laryngopharyngeal reflux (LPR) group. The general information, results of gastroscopy, 24 h esophageal impedance - pH monitoring and esophageal manometry, as well as the efficacy of proton pump inhibitor (PPI) were collected and compared between the two groups. Results: The proportion of esophagitis in GERD patients in typical symptom group was significantly increased than that in LPR group (P<0.05), while the values of mean nocturnal baseline impedance at 7-3 cm above lower esophageal sphincter (LES) were significantly lower (all P<0.05). Compared with typical symptom group, increased frequency of weak acid reflux, prolonged mean acid clearance time, higher LES relaxation rate, lower velocity of peristaltic waves at 11-7 cm above LES, and poor efficacy of PPI treatment were observed in LPR group (all P<0.05). The severity of heartburn was positively correlated with the percentage of total acid exposure time and DeMeester score (all P<0.05); while the severity of foreign body sensation was positively correlated with the frequency of weak acid reflux and mean time of acid clearance (all P<0.05). Conclusions: The esophageal mucosal injury was mild in GERD patients complicated with laryngopharyngeal symptoms. Laryngopharyngeal symptoms are more likely to be associated with the decreased acid clearance capacity due to esophageal body dysmotility. Strengthened acid suppression therapy should be recommended.

Objective:To analyze the effect of endovascular therapy (including balloon dilation, debulking and anti-restenosis technique) for below-the-ankle atherosclerotic lesions in chronic limb threatening ischemic patients.Methods:A retrospective analysis was performed on the clinical data of 465 patients (570 limbs) with below-the-ankle atherosclerosis who were consecutively admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2018 to December 2021. All patients received balloon dilatation below the ankle artery as basic treatment, including 67 patients in debulking subgroup, 82 patients in anti-restenosis subgroup and 11 patients in the triple therapy subgroup. The reocclusion rate, target lesion reintervention rate at 1, 3, 6 and 12 months after surgery were compared; The wound healing rate at 3 months, limb salvage rate at 6 and 12 months and mortality at 12 months in the Global Limb Anatomic Staging System (GLASS) grading groups P0, P1 and P2 were compared.Results:The technical success rate of this group was 76.0%(433 limbs/570 limbs). The follow-up rates of 6 and 12 months after operation were 85.4%(370 limbs/433 limbs) and 75.3%(326 limbs/433 limbs), respectively. The length of treated lesions was (3.6±1.3)cm; The reocclusion rates were 5.5%(23 limbs/420 limbs), 8.2%(33 limbs/403 limbs), 14.9%(55 limbs/370 limbs) and 23.6%(77 limbs/326 limbs) at 1, 3, 6 and 12 months after operation; The reintervention rate of target lesions in 6, 12 months was 7.6%(28 limbs/370 limbs) and 12.0%(39 limbs/326 limbs) respectively; The wound healing rate in groups P0, P1 and P2 within 3 months was 87.3%(192 limbs), 70.5%(62 limbs) and 10.5%(2 limbs) respectively ( P<0.001), the limb salvage rate in 6 months was 96.2%(200 limbs), 84.7%(127 limbs) and 33.3%(4 limbs) respectively ( P<0.001), and the limb salvage rate in 12 months was 78.7%(170 limbs), 54.5%(55 limbs) and 22.2%(2 limbs) respectively ( P<0.001). The mortality was 6.9%(32/465) 12 months after operation. Conclusions:Endovascular therapy below-the-ankle is feasible and has high technical success rate. The constitute integrity of pedal-plantar loop in limb- threatening phase is related to 3-month wound healing rate and limb salvage rate.