Omadacycline in the treatment of scrub typhus:Three case reports

BACKGROUND Scrub typhus is a naturally occurring acute infectious disease that is primarily transmitted through the bites of chiggers or larval mites infected by Orientia tsutsugamushi(O.tsutsugamushi).Omadacycline,a novel tetracycline,exhibits potent antibacterial efficacy against both typical bacteria and atypical pathogens.However,omadacycline application in the treatment of scrub typhus remains limited.CASE SUMMARY In the present work,we report several cases of scrub typhus,with the main clinical symptoms being fever,the formation of eschars or ulcers,local or systemic lymphadenopathy,headache,myalgia and rash.Blood samples were collected before omadacycline was administered,and O.tsutsugamushi infection was confirmed through targeted next-generation sequencing(tNGS).After two days of treatment,the patients’symptoms,including fever,were alleviated,with no adverse drug reactions.CONCLUSION tNGS is an effective method for diagnosing scrub typhus.Omadacycline can be considered an alternative option for antiinfective therapy in patients with O.tsutsugamushi infections.

Modified Appleby operation for carcinoma of the pancreatic body and tail

This is a case of a pancreatic tumor with invasion of the celiac stem treated using the modified Appleby operation.Preoperatively,routine B-ultrasound,computed tomography,and magnetic resonance imaging were performed.In the perioperative period,the combined gallbladder was excised;the duration of the operation was 5 h and volume of blood loss was approximately 500 ml.Postoperatively,the liver function temporarily returned and after a liver protection treatment,it returned to normal within 2 weeks.The liver had normal arterial blood supply,and the postoperative course was uneventful.It is safe and feasible to resect the whole pancreatic body and tail tumor combined with celiac stem resection.It can improve the resection rate of tumor and relieve pain.

Fecal microbiota transplantation alleviates experimental colitis through the Toll-like receptor 4 signaling pathway

BACKGROUND Fecal microbiota transplantation(FMT)has shown promising therapeutic effects on mice with experimental colitis and patients with ulcerative colitis(UC).FMT modulates the Toll-like receptor 4(TLR4)signaling pathway to treat some other diseases.However,it remains unknown whether this modulation is also involved in the treatment of UC.AIM To clarify the necessity of TLR4 signaling pathway in FMT on dextran sodium sulphate(DSS)-induced mice and explain the mechanism of FMT on UC,through association analysis of gut microbiota with colon transcriptome in mice.METHODS A mouse colitis model was constructed with wild-type(WT)and TLR4-knockout(KO)mice.Fecal microbiota was transplanted by gavage.Colon inflammation severity was measured by disease activity index(DAI)scoring and hematoxylin and eosin staining.Gut microbiota structure was analyzed through 16S ribosomal RNA sequencing.Gene expression in the mouse colon was obtained by transcriptome sequencing.RESULTS The KO(DSS+Water)and KO(DSS+FMT)groups displayed indistinguishable body weight loss,colon length,DAI score,and histology score,which showed that FMT could not inhibit the disease in KO mice.In mice treated with FMT,the relative abundance of Akkermansia decreased,and Lactobacillus became dominant.In particular,compared with those in WT mice,the scores of DAI and colon histology were clearly decreased in the KO-DSS group.Microbiota structure showed a significant difference between KO and WT mice.Akkermansia were the dominant genus in healthy KO mice.The ineffectiveness of FMT in KO mice was related to the decreased abundance of Akkermansia.Gene Ontology enrichment analysis showed that differentially expressed genes between each group were mainly involved in cytoplasmic translation and cellular response to DNA damage stimulus.The top nine genes correlating with Akkermansia included Aqp4,Clca4a,Dpm3,Fau,Mcrip1,Meis3,Nupr1 L,Pank3,and Rps13(|R|>0.9,P<0.01).CONCLUSION FMT may ameliorate DSS-induced colitis by regulating the TLR4 signaling pathway.TLR4 modulates the composition of gut microbiota and the expression of related genes to ameliorate colitis and maintain the stability of the intestinal environment.Akkermansia bear great therapeutic potential for colitis.

Anti-reflux effects of a novel esophagogastric asymmetric anastomosis technique after laparoscopic proximal gastrectomy

BACKGROUND Reflux esophagitis is a common postoperative complication of proximal gastrectomy.There is an urgent need for a safer method of performing esophageal-gastric anastomosis that reduces the risk of reflux after proximal gastrectomy.We hypothesize that a novel technique termed esophagogastric asymmetric anastomosis(EGAA)can prevent postoperative reflux in a safe and feasible manner.To observe a novel method of EGAA to prevent postoperative reflux.METHODS Initially,we employed a thermal stress computer to simulate and analyze gastric peristalsis at the site of an esophagogastric asymmetric anastomosis.This was done in order to better understand the anti-reflux function and mechanism.Next,we performed digestive tract reconstruction using the EGAA technique in 13 patients who had undergone laparoscopic proximal gastrectomy.Post-surgery,we monitored the structure and function of the reconstruction through imaging exams and gastroscopy.Finally,the patients were followed up to assess the efficacy of the anti-reflux effects.RESULTS Our simulation experiments have demonstrated that the clockwise contraction caused by gastric peristalsis and the expansion of the gastric fundus caused by the increase of intragastric pressure could significantly tighten the anastomotic stoma,providing a means to prevent the reverse flow of gastric fluids.Thirteen patients with esophagogastric junction tumors underwent laparoscopic proximal gastrectomy,with a mean operation time of 304.2±44.3 min.After the operation,the upper gastroenterography in supine/low head positions showed that eight patients exhibited no gastroesophageal reflux,three had mild reflux,and two had obvious reflux.The abdominal computed tomography examination showed a valve-like structure at the anastomosis.During followup,gastroscopy revealed a closed valve-like form at the anastomosis site without stenosis or signs of reflux esophagitis in 11 patients.Only two patients showed gastroesophageal reflux symptoms and mild reflux esophagitis and were treated with proton pump inhibitor therapy.CONCLUSION EGAA is a feasible and safe surgical method,with an excellent anti-reflux effect after proximal gastrectomy.

Dynamic expression of Slit1–3 and Robo1–2 in the mouse peripheral nervous system after injury

The Slit family of axon guidance cues act as repulsive molecules for precise axon pathfinding and neuronal migration during nervous system development through interactions with specific Robo receptors.Although we previously reported that Slit1–3 and their receptors Robo1 and Robo2 are highly expressed in the adult mouse peripheral nervous system,how this expression changes after injury has not been well studied.Herein,we constructed a peripheral nerve injury mouse model by transecting the right sciatic nerve.At 14 days after injury,quantitative real-time polymerase chain reaction was used to detect mRNA expression of Slit1–3 and Robo1–2 in L4–5 spinal cord and dorsal root ganglia,as well as the sciatic nerve.Immunohistochemical analysis was performed to examine Slit1–3,Robo1–2,neurofilament heavy chain,F4/80,and vimentin in L4–5 spinal cord,L4 dorsal root ganglia,and the sciatic nerve.Co-expression of Slit1–3 and Robo1–2 in L4 dorsal root ganglia was detected by in situ hybridization.In addition,Slit1–3 and Robo1–2 protein expression in L4–5 spinal cord,L4 dorsal root ganglia,and sciatic nerve were detected by western blot assay.The results showed no significant changes of Slit1–3 or Robo1–2 mRNA expression in the spinal cord within 14 days after injury.In the dorsal root ganglion,Slit1–3 and Robo1–2 mRNA expression were initially downregulated within 4 days after injury;however,Robo1–2 mRNA expression returned to the control level,while Slit1–3 mRNA expression remained upregulated during regeneration from 4–14 days after injury.In the sciatic nerve,Slit1–3 and their receptors Robo1–2 were all expressed in the proximal nerve stump;however,Slit1,Slit2,and Robo2 were barely detectable in the nerve bridge and distal nerve stump within 14 days after injury.Slit3 was highly ex-pressed in macrophages surrounding the nerve bridge and slightly downregulated in the distal nerve stump within 14 days after injury.Robo1 was upregulated in vimentin-positive cells and migrating Schwann cells inside the nerve bridge.Robo1 was also upregulated in Schwann cells of the distal nerve stump within 14 days after injury.Our findings indicate that Slit3 is the major ligand expressed in the nerve bridge and distal nerve stump during peripheral nerve regeneration,and Slit3/Robo signaling could play a key role in peripheral nerve repair after injury.This study was approved by Plymouth University Animal Welfare Ethical Review Board (approval No.30/3203) on April 12,2014.

Colorectal adenocarcinoma patients with M1a diseases gain more clinical benefits from palliative primary tumor resection than those with M1b diseases: A propensity score matching analysis

BACKGROUND Surgical resection is regarded as the only potentially curative treatment option for patients with metastatic colorectal cancer(CRC).The National Comprehensive Cancer Network clinical practice guidelines do not recommend palliative surgery unless there is a risk of severe symptoms.However,accumulating evidence has shown that palliative surgery is associated with more favorable outcomes for patients with metastatic CRC.AIM To investigate the separate role of palliative primary tumor resection for patients with stage IVA(M1a diseases)and stage IVB(M1b diseases)colorectal adenocarcinoma(CRA).METHODS CRA patients diagnosed from 2010 to 2015 with definite M1a and M1b categories according to the 8th edition of American Joint Committee on Cancer staging system were selected from the Surveillance Epidemiology and End Results(SEER)database.To minimize potential selection bias,the data were adjusted by propensity score matching(PSM).Baseline characteristics,including gender,year of diagnosis,age,marital status,primary site,surgical information,race,grade,chemotherapy,and radiotherapy,were recorded and analyzed.Univariate and multivariate analyses were performed to explore the separate role of palliative surgery for patients with M1a and M1b diseases.RESULTS A total of 19680 patients with metastatic CRA were collected from the SEER database,including 10399 cases of M1a diseases and 9281 cases of M1b diseases.Common independent prognostic factors for both M1a and M1b patients included year of diagnosis,age,race,marital status,primary site,grade,surgery,and chemotherapy.After PSM adjustment,3732 and 3568 matched patients in the M1a and M1b groups were included,respectively.Patients receiving palliative primary tumor resection had longer survival time than those without surgery(P<0.001).For patients with M1a diseases,palliative resection could increase the median survival time by 9 mo;for patients with M1b diseases,palliative resection could prolong the median survival time by 7 mo.For M1a diseases,patients with lung metastasis had more clinical benefit from palliative resection than those with liver metastasis(15 mo for lung metastasis vs 8 mo for liver metastasis,P<0.001).CONCLUSION CRA patients with M1a diseases gain more clinical benefits from palliative primary tumor resection than those with M1b diseases.Those patients with M1a(lung metastasis)have superior long-term outcomes after palliative primary tumor resection.

Synchronous parathyroid adenoma, papillary thyroid carcinoma and thyroid adenoma in pregnancy: A case report

BACKGROUND There is a common pathologic relationship between parathyroid adenoma and thyroid cancer,but this relationship is infrequent in pregnant patients with primary hyperparathyroidism(PHPT).CASE SUMMARY A 27-year-old gravida 1 woman was transferred to our hospital at 16 wk of pregnancy.She was diagnosed with parathyroidoma,papillary carcinoma of the thyroid and thyroid adenoma and was managed surgically.Both the mother and the newborn were stable after a right inferior parathyroidectomy and total thyroidectomy.The healthy infant was delivered at the 40th week of pregnancy.The mother had no evidence of recurrence over three years of follow-up.CONCLUSION Awareness of concomitant PHPT and thyroid diseases may help in managing patients with a history of hypercalcemia.

Prognostic role of pretreatment serum ferritin concentration in lung cancer patients:A meta-analysis

BACKGROUND The association between pretreatment serum ferritin concentration(SFC)and long-term survival in lung cancer remains unclear now.AIM To identify the prognostic value of pretreatment SFC in lung cancer patients based on current evidence.METHODS The PubMed,EMBASE and Web of Science databases were searched from inception to May 29,2022 for relevant studies.The primary endpoint was overall survival(OS)and the hazard ratios(HRs)with corresponding 95%confidence intervals(CIs)were combined to assess the predictive role of pretreatment SFC for long-term survival of lung cancer patients.The data were then extracted and assessed on the basis of the Reference Citation Analysis(https://www.reference citationanalysis.com/).RESULTS Twelve retrospective studies involving 1654 patients were analyzed.The results manifested that increased pretreatment SFC was associated with worse OS(HR=1.09,95%CI:1.03-1.15,P=0.004).Subgroup analysis stratified by the country(China vs non-China)showed similar results.However,subgroup analysis stratified by tumor type revealed inconsistent results(lung cancer:HR=1.39,P=0.008;small cell lung cancer:HR=1.99,P=0.175;non-small cell lung cancer:HR=1.03,P=0.281).CONCLUSION Pretreatment SFC might serve as a promising prognostic indicator in lung cancer patients and elevated pretreatment SFC predicts worse prognosis.However,more high-quality studies with big sample sizes are still needed to further verify its prognostic value in lung cancer.

Clinical and microbiological characteristics of patients with biliary disease

BACKGROUND Biliary diseases are common digestive system disorders which may combine with biliary tract infection such as cholecystitis or cholangitis.Thus,rapid identification of the bacteria and their antibiotic susceptibility profiles are crucial for reducing the mortality of patients with biliary tract infection.AIM To identify bacterial species and antibiotic susceptibility for antibacterial therapy and analyze bile cultivation risk factors for increasing detection rates.METHODS This retrospective study was conducted from July 2008 to July 2017.In total,1339 bile samples which were collected during therapeutic endoscopic retrograde cholangiopan-creatography or percutaneous transhepatic cholangiodrainage or other biliary surgeries or biliary drainage were obtained to characterize pathogen spectra,antibiotic susceptibility,and clinical features.Clinical data including age,sex,comorbidities,clinical symptoms,protopathies,and history of biliary tract diseases and surgeries were collated from hospital medical records.Species identification and initial drug susceptibility were further identified by biochemical characterization using the VITEK 2 Compact test.RESULTS Positive microbiological findings were observed in 738 samples.The most frequently encountered strains were gram-negative bacteria(74.94%),including Escherichia coli(37.78%),Pseudomonas aeruginosa(8.96%),and Klebsiella pneumoniae(10.29%).Bile bacteria were largely sensitive to carbapenems,piperacillin/tazobactam,and gentamicin.Gram-negative strains had low susceptibility to ceftriaxone,quinolones and ampicillin.Almost the same microorganisms were present in patients with malignant and benign diseases.The number of samples with Klebsiella pneumoniae in the bile culture were significantly different between patients with malignant and benign diseases(55 vs 30;P=0.019).Age(P<0.001),fever(P<0.001),history of biliary tract diseases and surgeries(both P<0.001),benign disease(P=0.002),and the comorbidity chronic renal insufficiency(P=0.007)affected the positive rates of the bile samples.CONCLUSION Gram-negative bacteria were the most commonly isolated biliary bacteria.We determined the major factors associated with positive detection rates.Microbiological analysis of bile samples allowed accurate antibiotic treatments.

Effective immune-inflammation index for ulcerative colitis and activity assessments

BACKGROUND The inverse association between systemic immune-inammation index(SII)and overall survival in tumors has been studied.AIM To evaluate the hematological indexes for assessing the activity of ulcerative colitis(UC).METHODS In this case-control study,172 UC patients and healthy participants were included.Comparisons were made among groups of white blood cells,hemoglobin,platelets,neutrophils,lymphocytes,monocytes,SII,neutrophil-tolymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).The relationship with hematological inflammation was verified by Spearman correlation analyses.The efficiency of SII,NLR,and PLR for distinguishing between UC and severe disease status was assessed by the receiver operator curve and logistic regression analyses.RESULTS The values of SII,NLR,and PLR were higher in UC patients than in controls(P<0.001)and were positively correlated with the Mayo endoscopic score,extent,Degree of Ulcerative Colitis Burden of Luminal Inflammation(DUBLIN)score,and Ulcerative Colitis Endoscopic Index of Severity(UCEIS).The cut-off NLR value of 562.22 predicted UC with a sensitivity of 79.65%and a specificity of 76.16%.Logistic regression analysis revealed that patients with SII and NLR levels above the median had a significantly higher risk of UC(P<0.05).Risk factors independently associated with DUBLIN≥3 included SII≥1776.80[odds ratio(OR)=11.53,P=0.027]and NLR value of 2.67-4.23(OR=2.96,P=0.047)on multivariate analysis.Compared with the first quartile,SII≥1776.80 was an independent predictor of UCEIS≥5(OR=18.46,P=0.012).CONCLUSION SII has a certain value in confirming UC and identifying its activity.

Fecal microbiota transplantation ameliorates experimental colitis via gut microbiota and T-cell modulation

BACKGROUND Emerging evidence has demonstrated that fecal microbiota transplantation(FMT)has a promising therapeutic effect on mice with experimental colitis and patients with ulcerative colitis(UC),although the mechanism of FMT is unclear.AIM To evaluate the protective effect of FMT on UC and clarify its potential dependence on the gut microbiota,through association analysis of gut microbiota with colon transcriptome in mice.METHODS Dextran sodium sulfate(DSS)-induced experimental colitis was established and fecal microbiota was transplanted by gavage.Severity of colon inflammation was measured by body weight,disease activity index,colon length and histological score.Gut microbiota alteration was analyzed through 16S ribosomal ribonucleic acid sequencing.The differentially expressed genes(DEGs)in the colon were obtained by transcriptome sequencing.The activation status of colonic T lymphocytes in the lamina propria was evaluated by flow cytometry.RESULTS Compared with the DSS group,the weight loss,colon length shortening and inflammation were significantly alleviated in the FMT group.The scores of disease activity index and colon histology decreased obviously after FMT.FMT restored the balance of gut microbiota,especially by upregulating the relative abundance of Lactobacillus and downregulating the relative abundance of Clostridium_sensu_stricto_1 and Turicibacter.In the transcriptomic analysis,128 DEGs intersected after DSS treatment and FMT.Functional annotation analysis suggested that these DEGs were mainly involved in T-lymphocyte activation.In the DSS group,there was an increase in colonic T helper CD4^(+)and T cytotoxic CD8^(+)cells by flow cytometry.FMT selectively downregulated the ratio of colonic CD4^(+)and CD8^(+)T cells to maintain intestinal homeostasis.Furthermore,Clostri dium_sensu_stricto_1 was significantly related to inflammation-related genes including REG3G,CCL8 and IDO1.CONCLUSION FMT ameliorated DSS-induced colitis in mice via regulating the gut microbiota and T-cell modulation.

Targeting tumor endothelial hyperglycolysis enhances immunotherapy through remodeling tumor microenvironment

Vascular abnormality is a hallmark of most solid tumors and facilitates immune evasion.Targeting the abnormal metabolism of tumor endothelial cells(TECs)may provide an opportunity to improve the outcome of immunotherapy.Here,in comparison to vascular endothelial cells from adjacent peritumoral tissues in patients with colorectal cancer(CRC),TECs presented enhanced glycolysis with higher glyceraldehyde-3-phosphate dehydrogenase(GAPDH)expression.Then an unbiased screening identified that osimertinib could modify the GAPDH and thus inhibit its activity in TECs.Low-dose osimertinib treatment caused tumor regression with vascular normalization and increased infiltration of immune effector cells in tumor,which was due to the reduced secretion of lactate from TECs by osimertinib through the inhibition of GAPDH.Moreover,osimertinib and anti-PD-1 blockade synergistically retarded tumor growth.This study provides a potential strategy to enhance immunotherapy by targeting the abnormal metabolism of TECs.

Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients

BACKGROUND Transendoscopic enteral tubing(TET)has been used in China as a novel delivery route for fecal microbiota transplantation(FMT)into the whole colon with a high degree of patient satisfaction among adults.AIM To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease(IBD).METHODS An anonymous questionnaire,evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China.Question formats included single-choice questions,multiple-choice questions and sorting questions.Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET.Patients who had experience of FMT,the way they underwent FMT and acceptance of TET were the main interest.Then all the patients were asked whether they would recommend FMT and TET.This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it.RESULTS A total of 620 eligible questionnaires were included in the analysis.The survey showed that 44.6%(228/511)of patients did not know that FMT is a therapeutic option in IBD,and 80.6%(412/511)of them did not know the concept of TET.More than half(63.2%,323/511)of the participants stated that they would agree to undergo FMT through TET.Of the patients who underwent FMT via TET[62.4%(68/109)],the majority[95.6%(65/68)]of them were satisfied with TET.Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not(94.5%vs 86.3%,P=0.018 and 98.5%vs 87.8%,P=0.017).Patients’choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT.When compared to patients without experience of FMT,Crohn’s disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET(P<0.001)and colonic TET(P<0.001),respectively.CONCLUSION Patients’experience of FMT through TET lead them to maintain a positive attitude towards FMT.The present findings highlighted the significance of patient education on FMT and TET.

Mining Syndrome Differentiating Principles from Traditional Chinese Medicine Clinical Data

Syndrome differentiation-based treatment is one of the key characteristics of Traditional Chinese Medicine(TCM).The process of syndrome differentiation is difficult and challenging due to its complexity,diversity and vagueness.Analyzing syndrome principles from historical records of TCM using data mining(DM)technology has been of high interest in recent years.Nevertheless,in most relevant studies,existing DM algorithms have been simply developed for TCM mining,while the combination of TCM theories or its characteristics with DM algorithms has rarely been reported.This paper presents a novel Symptom-Syndrome Topic Model(SSTM),which is a supervised probabilistic topic model with three-tier Bayesian structure.In the SSTM,syndromes are considered as observed topic labels to distinguish certain symptoms from possible symptoms according to their different positions.The generation of our model is in full compliance with the syndrome differentiation theory of TCM.Experimental results show that the SSTM is more effective than other models for syndrome differentiating.

Treatment of dilated cardiomyopathy caused by coronary microvascular dysfunction with anisodamine: a report of 5 cases

The management of dilated cardiomyopathy(DCM) is well established. However, a subset of patients does not have recovery from or have recurrences of left ventricular(LV) dysfunction despite receiving optimal medical therapy. Coronary microvascular dysfunction(CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. Dilated myocardial phenotype may be responsible for CMD in DCM. Anisodamine can exert a significant effect on relieving microvascular spasm, and improving and dredging the coronary microcirculation. However,whether CMD can be potentially improved with anisodamine to make DCM better remains incompletely understood.

Factors Associated with Thrombolysis Outcome in Ischemic Stroke Patients with Atrial Fibrillation

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation（AF）is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome（P ／ 0.001） and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were：heart failure（P = 0.045）; high systolic pressure（P = 0.039）; high blood glucose（P = 0.030）; and a high National Institutes of Health Stroke Scale（NIHSS） score（P ／ 0.001）. Moreover, high systolic pressure at admission（P = 0.007）, high blood glucose（P = 0.027）, and a high NIHSS score（P ／ 0.001） were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score（P = 0.006） and warfarin taken within 48 h before stroke onset（P = 0.032） were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke.