Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

Adipose-derived stem cells in diabetic foot care:Bridging clinical trials and practical application

Diabetic foot ulcers(DFUs)pose a critical medical challenge,significantly impairing the quality of life of patients.Adipose-derived stem cells(ADSCs)have been identified as a promising therapeutic approach for improving wound healing in DFUs.Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU,its clinical applications remain elusive.In this review,we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs.The review begins with a discussion of the classification and clinical management of diabetic foot conditions.It then discusses the current landscape of clinical trials,focusing on their geographic distribution,reported efficacy,safety profiles,treatment timing,administration techniques,and dosing considerations.Finally,the review discusses the preclinical strategies to enhance ADSC efficacy.This review shows that many trials exhibit biases in study design,unclear inclusion criteria,and intervention protocols.In conclusion,this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches,with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

Effectiveness of negative pressure wound therapy in complex surgical treatment of necrotizing fasciitis of the upper limb

BACKGROUND Necrotizing fasciitis(NF)of the upper extremities is a severe surgical pathology,and the incidence of this disease has been steadily increasing in recent decades.Surgical treatment is accompanied by the formation of extensive wounds,which can be treated with significant difficulties.In recent years,negative pressure wound therapy(NPWT)has proven to be highly effective.It is also promising for the treatment of NF.AIM To explore the effectiveness of NPWT in the treatment of NF of the upper extremities.METHODS The results of the treatment of 36 patients with NF of the upper extremities in two groups(NPWT group and control group;2022−2023)were retrospectively analyzed.In the NPWT group,the NPWT method(120 mmHg;constant mode)was used after surgical treatment.The number of vacuum-assisted dressings in patients ranged from 1 to 3,depending on the dynamics of the wound process.The duration of fixation of one bandage was up to 2−3 d.In the control group,conventional methods of local wound treatment were used.The following indicators were analyzed:The treatment delay,the prevalence of inflammation,the microbial landscape,the number of debridements,the duration of wound preparation for surgical closure,and the nature of skin plastic surgery.RESULTS Most patients experienced a significant treatment delay[4 d,interquartile range(IQR):2–7 d],which led to the spread of the pathological process to the forearm and shoulder.The most common pathogens were Staphylococcus aureus(14;38.9%)and Streptococcus pyogenes(22;61.1%).The average number of debridements per patient was 5(IQR:3–7),with no difference between groups.The average time to prepare wounds for surgical closure was 11±4 d in the NPWT group and 29±10 d(P=0.00001)in the control group.In the NPWT group,the wounds were more often closed with local tissues(15;83.3%),and in the control group,split-thickness skin grafts were more often used(4;50%).CONCLUSION The predominant isolation of Staphylococcus aureus and/or Streptococcus pyogenes from the lesions allowed us to classify these patients as NF type II.Multiple debridement procedures have become a feature of this disease treatment.The use of NPWT has significantly reduced the time required to prepare wounds for surgical closure.Early closure of wounds allows for more frequent use of local tissue repair,which ensures better results.NPWT is a highly effective way to prepare wounds for early surgical closure in patients with upper extremity NF.

A novel saliva-based miRNA profile to diagnose and predict oral cancer

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

Identification and Distribution of the Clinical Isolates of Imipenem-resistant Pseudomonas aeruginosa Carrying Metallo-β-lactamase and/or Class 1 Integron Genes

To investigate the distribution of the genes of two major metallo-β-1actamases （MBL;i.e.,IMP and VIM） and class 1 integrons （intI） in the clinical imipenem-resistant Pseudomonas aeruginosa, a total of 65 isolates, from a university hospital in Sichuan between December 2004 and April 2005 were screened for MBL genes by PCR using primers specific for blaIMP-1, blaVIM and blaVIM-2 genes. The MBL-positive isolates were further assessed for class 1 integrons by PCRusing specific primers. The nucleotide sequences of several PCR products were also determined. The results revealed that the blaVIM gene was found in 81.5% （53/65） of all isolates, blaVIM-2 gene was found in only 1 isolate and the intl gene was observed in 45.3% （24/53） of blaVIM-positive isolates. One isolate carried simultaneously both blaIMP-1 and intl genes, and to the best of our knowledge this is the first report of such isolate in southwest China. These observations highlight that the genes for VIM β-1actamase and class 1 integrons were predominantly present among the imipenem-resistant P. aeruginosa tested, confirming the current widespread threat of imipenem-resistant, integron-borne P.aeruginosa.

Epidemiological and clinical characteristics of COVID-19 patients in Hengyang,Hunan Province,China

BACKGROUND In December 2019,an ongoing outbreak of coronavirus disease 2019(COVID-19)was first identified in Wuhan,China.The characteristics of COVID-19 patients treated in local hospitals in Wuhan are not fully representative of patients outside Wuhan.Therefore,it is highly essential to analyze the epidemiological and clinical characteristics of COVID-19 in areas outside Wuhan or Hubei Province.To date,a limited number of studies have concentrated on the epidemiological and clinical characteristics of COVID-19 patients with different genders,clinical classification,and with or without basic diseases.AIM To study the epidemiological and clinical characteristics of COVID-19 patients in Hengyang(China)and provide a reliable reference for the prevention and control of COVID-19.METHODS From January 16 to March 2,2020,a total of 48 confirmed cases of COVID-19 were reported in Hengyang,and those cases were included in this study.The diagnostic criteria,clinical classification,and discharge standard related to COVID-19 were in line with the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia(Trial Version 7)released by National Health Commission and National Administration of Traditional Chinese Medicine.The presence of SARS-CoV-2 in pharyngeal swab specimens was detected by quantitative reverse transcription polymerase chain reaction.All the data were imported into the excel worksheet and statistically analyzed by using SPSS 25.0 software.RESULTS A total of 48 cases of COVID-19 were collected,of which 1 was mild,38 were moderate,and 9 were severe.It was unveiled that there were 31(64.6%)male patients and 17(35.4%)female patients,with a female-to-male ratio of 1.82:1.The range of age of patients with COVID-19 was dominantly 30-49 years old[25(52.1%)of 48],followed by those aged over 60 years old[11(22.9%)].Besides,29.2%(14 of 48)of patients had basic diseases,and 57.2%(8 of 14)of patients with basic diseases were aged over 60 years old.The occupations of 48 COVID-19 patients were mainly farmers working in agricultural production[15(31.5%)of 48],rural migrant workers from Hengyang to Wuhan[15(31.5%)],and service workers operating in the service sector[8(16.7%)].The mean latent period was 6.86±3.57 d,and the median was 7[interquartile range(IQR):4-9]d.The mean time from onset of symptoms to the first physician visit was 3.38±2.98(95%CI:2.58-9.18)d,with a median of 2(IQR:1-5)d,and the mean time from hospital admission to confirmed diagnosis was 2.29±2.11(95%CI:1.18-6.42)d,with a median of 2(IQR:1-3)d.The main symptoms were fever[43(89.6%)of 48],cough and expectoration[41(85.4%)],fatigue[22(45.8%)],and chills[22(45.8%)].Other symptoms included poor appetite[13(27.1%)],sore throat[9(18.8%)],dyspnea[9(18.8%)],diarrhea[7(14.6%)],dizziness[5(10.4%)],headache[5(10.4%)],muscle pain[5(10.4%)],nausea and vomiting[4(8.3%)],hemoptysis[4(8.3%)],and runny nose[1(2.1%)].The numbers of peripheral blood leukocytes,lymphocytes,and eosinophils were significantly reduced in the majority of the patients.The levels of C-reactive protein,fibrinogen,blood glucose,lactate dehydrogenase,Ddimer,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(γ-GT),myoglobin(MB),and creatine kinase(CK)were increased in 64.6%,44.7%,43.2%,37.0%,29.5%,22.9%,20.8%,21.6%,13.6%,and 12.8%of patients,respectively.The incidence of ALT elevation in male patients was remarkably higher than that in females(P<0.01),while the incidences of AST,CK,and blood glucose elevations in severe patients were remarkably higher than those in moderate patients(P<0.05,respectively).Except for the mild patients,chest computed tomography showed characteristic pulmonary lesions.All the patients received antiviral drugs,38(79.2%)accepted traditional Chinese medicine,and 2(4.2%)received treatment of human umbilical-cord mesenchymal stem cells.On March 2,2020,48 patients with COVID-19 were all cured and discharged.CONCLUSION Based on our results,patients with COVID-19 often have multiple organ dysfunction or damage.The incidences of ALT elevation in males,and AST,CK,and blood glucose elevations in severe patients are remarkably higher.

Epidemiology of small intestinal bacterial overgrowth

Small intestinal bacterial overgrowth(SIBO)is defined as an increase in the bacterial content of the small intestine above normal values.The presence of SIBO is detected in 33.8%of patients with gastroenterological complaints who underwent a breath test,and is significantly associated with smoking,bloating,abdominal pain,and anemia.Proton pump inhibitor therapy is a significant risk factor for SIBO.The risk of SIBO increases with age and does not depend on gender or race.SIBO complicates the course of a number of diseases and may be of pathogenetic significance in the development of their symptoms.SIBO is significantly associated with functional dyspepsia,irritable bowel syndrome,functional abdominal bloating,functional constipation,functional diarrhea,short bowel syndrome,chronic intestinal pseudo-obstruction,lactase deficiency,diverticular and celiac diseases,ulcerative colitis,Crohn’s disease,cirrhosis,metabolic-associated fatty liver disease(MAFLD),primary biliary cholangitis,gastroparesis,pancreatitis,cystic fibrosis,gallstone disease,diabetes,hypothyroidism,hyperlipidemia,acromegaly,multiple sclerosis,autism,Parkinson’s disease,systemic sclerosis,spondylarthropathy,fibromyalgia,asthma,heart failure,and other diseases.The development of SIBO is often associated with a slowdown in orocecal transit time that decreases the normal clearance of bacteria from the small intestine.The slowdown of this transit may be due to motor dysfunction of the intestine in diseases of the gut,autonomic diabetic polyneuropathy,and portal hypertension,or a decrease in the motor-stimulating influence of thyroid hormones.In a number of diseases,including cirrhosis,MAFLD,diabetes,and pancreatitis,an association was found between disease severity and the presence of SIBO.Further work on the effect of SIBO eradication on the condition and prognosis of patients with various diseases is required.

Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

Gastric acid plays an important role in digesting food （especially protein）, iron absorption, and destroying swallowed micro-organisms. H＋ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms. Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like （ECL） cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, longterm hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastdn levels, leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concem, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and dinically in the regulation of gastric acid secretion.

Clinical Predictors for Reduced Long-Term Survival and Cause of Death after Curative Resection for Rectal Cancer

Purpose: To identify clinical predictors for reduced long-term survival and describe the cause of death after surgical treatment for rectal cancer. Methods: A retrospective follow-up study of 442 consecutive, unselected patients treated for rectal cancer at a tertiary centre from 1990 until 2000 and followed for 17 years or until death. Predictors for death were assessed by Cox regression analysis. The cause of death was obtained from the Norwegian Cause of Death Registry. Results: 254 men and 188 women with a median age of 71 years (21 - 95 years) were resected for rectal cancer with low anterior resection (n = 266), abdominoperineal resection (n = 125), Hartmann’s procedure (n = 19) or diverting stoma only (n = 32). Median follow-up was 5 years (0 - 17 years). The relative five-year survival rates for stages I, II, III and IV was 83.9%, 65.2%, 41.1% and 9.3%, respectively. The proportion of deaths due to recurrence from colorectal cancer in stages I, II, III and IV was 23.5%, 55.8%, 72.3% and 98.0%, respectively. Heart, lung and cerebrovascular disease and other malignancies were the cause of death in the other patients. Higher age, abdominoperineal resection compared to low anterior resection, lack of lymph node dissection compared to total mesorectal excision (TME), postoperative reoperations, TNM stages II and III compared to stage I and residual tumours after surgery were all significant independent predictors of reduced survival in the adjusted Cox regression model. Conclusions: Age, tumour stage, type of surgery, lymph node dissection, residual tumour after surgery and reoperations are predictors for survival after surgery for rectal cancer. In the patients who died, the cause of death was due to a condition other than colorectal cancer recurrence in 32.3% of the patients. The five-year relative survival rate was related to tumour stage.

Meta-analysis of clinical efficacy and safety of kidney Tonifying therapy in the treatment of interstitial lung disease

Objective:To evaluate the efficacy and safety of kidney tonifying therapy in the treatment of Interstitial Lung Disease(ILD).Methods:We searched Wanfang Data,CNKI,CBM,VIP,Pub Med,EMBASE,Web of science and Cochrane Library for Randomized Controlled Trials(RCTs)of kidney tonifying therapy in the treatment of ILD.The retrieval time was from the establishment of the database to December 15,2020.Rev man 5.3 software was used to analyze and summarize the collected literature,and the methodological quality of the included studies was evaluated by the bias risk assessment scale of Cochrane Collaboration Network.Results:A total of 15 articles with 1045 patients were included.The results of meta-analysis showed that compared with the control group treated with conventional western medicine alone,kidney tonifying therapy or combined with conventional western medicine was beneficial to improve the clinical total effective rate[RR=1.33(95%CI 1.24-1.43),P<0.00001].At the same time,compared with the control group treated with routine western medicine,kidney tonifying therapy or combined with routine western medicine can improve cough and wheezing symptoms of patients[MD=-0.62(95%CI-0.78~-0.46),P<0.00001]and MD=-0.79(95%CI-0.18~-0.49),P<0.00001].However,there was no significant improvement in 6-minute walk test and lung function(DLCO%)(P>0.05);only one study reported 7 patients with adverse reactions,but after corresponding treatment,the symptoms were significantly relieved.The analysis of the characteristics of intervention measures in the treatment group showed that there were a total of 80 traditional Chinese medicines involved,of which Shu Dihuang appeared the most frequently,and the tonic drugs were used the most.The two meridians of the lung and kidney appear most frequently.Among the four qi and five flavors,warm and sweet medicines have the highest frequency.Conclusion:Adopting kidney-tonifying method or combined with conventional Western medicine treatment can improve the total clinical effectiveness of patients.Adopting kidney-tonifying method or combined with conventional Western medicine treatment to improve symptoms such as coughing and wheezing.No serious adverse reactions have been reported,and the safety is reliable.Due to the low quality of the included literature,the results of this study need to be verified by high-quality,large sample randomized controlled trials.

Cause of Death and Clinical Predictors of Survival after Curative Resection for Colon Cancer

Background: Clinical predictors of death and survival in surgical treatment of colon cancer are easily confounded by the modern adjuvant and neo-adjuvant chemotherapy. This study focuses on lethality and survival during implementation of ultra-radical surgery for colonic cancer prior to multimodal therapy. Methods: Retrospective observational follow-up study of 824 consecutive, unselected patients resected for Stage I, II, III and IV colon cancer from 1990 until 2000 at one tertiary centre, with a median follow-up of 45 months (0 - 202 months). Predictors for death were assessed by Cox regression analyses and log-rank test. The cause of death was obtained from the Norwegian Cause of Death Registry. Results: The relative survival rates were 86.3%, 71.9%, 50.3% and 6.6% in Stage I, II, III and IV, respectively. In 28.7% of the patients, the cause of death was other than colorectal cancer recurrence. The adjusted Cox regression model showed that higher age (1.04 (95% CI: 1.03;1.05)), male gender (1.37 (1.14;1.66)), emergency surgery (1.52 (1.21;1.93)), left vs. right hemicolectomy (1.39 (1.03;1.87)), and perioperative blood transfusion (1.25 (1.01;1.55)) were predictors of reduced survival. Health without known comorbidity (0.71 (0.58;0.88)), D2 versus D1 lymph node dissection (0.66 (0.53;0.83)) and tumour Stage I, II, III versus Stage IV 0.10 (0.06;0.16), 0.14 (0.11;0.19), 0.23 (0.18;0.30) were associated with prolonged survival. Conclusions: In 28.7% of the patients, the cause of death was other than colorectal cancer recurrence. Age, sex, comorbidity, emergency resection, lack of lymph node dissection, tumour stage, and preoperative blood transfusions are all significant predictors for reduced survival after surgery for colon cancer.

Effects of the number of neoadjuvant therapy cycles on clinical outcomes, safety, and survival in patients with metastatic colorectal cancer undergoing metastasectomy

The controversial outcomes in patients with metastatic colorectal cancer(mCRC)highlight the need for developing effective systemic neoadjuvant treatment strategies to improve clinical results.The optimal treatment cycles in patients with mCRC for metastasectomy remain undefined.This retrospective study compared the efficacy,safety,and survival of cycles of neoadjuvant chemotherapy/targeted therapy for such patients.Sixty-four patients with mCRC who received neoadjuvant chemotherapy/targeted therapy following metastasectomy were enrolled between January 2018 and April 2022.Twenty-eight patients received 6 cycles of chemotherapy/targeted therapy,whereas 36 patients received≥7 cycles(median,13;range,7–20).Clinical outcomes,including response,progression-free survival(PFS),overall survival(OS),and adverse events,were compared between these two groups.Of the 64 patients,47(73.4%)were included in the response group,and 17(26.6%)were included in the nonresponse group.The analysis revealed chemotherapy/targeted therapy cycle and pretreatment serum carcinoembryonic antigen(CEA)level as independent predictors of the response as well as overall survival and chemotherapy/targeted therapy cycle as an independent predictor of progression(all p<0.05).Furthermore,our results revealed shorter operation time,lower estimated operative blood loss,higher response rate,lower progression rate,and higher survival rate in≥7 cycles of chemotherapy/targeted therapy group(all p<0.05),but no statistical differences in adverse events were observed between the two groups(all p>0.05).The median OS and PFS were 48 months(95%CI,40.855–55.145)and 28 months(95%CI,18.952–37.48)in the≥7-cycle group and 24 months(95%CI,22.038–25.962)and 13 months(95%CI,11.674–14.326)in the 6-cycle group,respectively(both p<0.001).The oncological outcomes in the≥7-cycle group were significantly better than those in the 6-cycle group,without significant increases in adverse events.However,prospective randomized trials are mandatory to confirm the potential advantages of cycle numbers of neoadjuvant chemotherapy/targeted therapy.

Multiple flexor tendon ruptures due to osteochondroma of the hamate:A case report

BACKGROUND Closed rupture of the little and ring finger flexor tendons caused by the hamate is mostly associated with a fracture or nonunion of the hamate hook.Only one case of a closed rupture of the finger flexor tendon caused by osteochondroma in the hamate has been reported.Here,we present a case study to highlight the possibility of hamate osteochondroma as a rare cause of finger closed flexor tendon rupture based on our clinical experience and literature review.CASE SUMMARY A 48-year-old man who had been a rice-field farmer for 7–8 h a day for the past 30 years visited our clinic due to the loss of right little finger and ring finger flexion involving both the proximal and distal interphalangeal joints.The patient was diagnosed with a complete rupture of the ring and little finger flexors because of the hamate and was pathologically diagnosed with an osteochondroma.Exploratory surgery was performed,and a complete rupture of the ring and little finger flexors due to an osteophyte-like lesion of the hamate was observed,which was pathologically diagnosed as an osteochondroma.CONCLUSION One should consider that osteochondroma in the hamate may be the cause of closed tendon ruptures.

Classification of hepatobiliary scintigraphy patterns in segmented gallbladder according to anatomical discordance

BACKGROUND Hepatobiliary scintigraphy(HBS)is a useful diagnostic imaging technique that uses radiotracers to evaluate the function of the gallbladder(GB)and biliary system.In segmented GB,some HBS images reveal a discordant GB boundary as compared to anatomical images.AIM To evaluate the characteristics of HBS in segmented GB and determine the clinical relevance according to HBS characteristics.METHODS A total of 268 patients with chronic cholecystitis,gallstones,or biliary colic symptoms who underwent HBS between 2011 and 2020 were enrolled.Segmented GB was defined as segmental luminal narrowing of the GB body on computed tomography(CT)or magnetic resonance(MR)images,and HBS was examined 1 mo before or after CT or MR.Segmented GB was classified into 3 types based on the filling and emptying patterns of the proximal and distal segments according to the characteristics of HBS images,and GB ejection fraction(GBEF)was identified:Type 1 was defined as a normal filling and emptying pattern;Type 2 was defined as an emptying defect on the distal segment;and Type 3 was defined as a filling defect in the distal segment.RESULTS Segmented GB accounted for 63 cases(23.5%),including 36 patients(57.1%)with Type 1,18 patients(28.6%)with Type 2,and 9 patients(14.3%)with Type 3 emptying pattern.Thus,approximately 43%of HBS images showed a discordant pattern as compared to anatomical imaging of segmented GB.Although there were no significant differences in clinical symptoms,rate of cholecystectomy,or pathological findings based on the type,most gallstones occurred in the distal segment.Reported GBEF was 62.50%±24.79%for Type 1,75.89%±17.21%for Type 2,and 88.56%±7.20%for Type 3.Type 1 showed no difference in reported GBEF compared to the non-segmented GB group(62.50%±24.79%vs 67.40%±21.78%).In contrast,the reported GBEF was higher in Types 2 and 3 with defective emptying and filling when compared to Type 1(80.11%±15.70%vs 62.57%±24.79%;P=0.001).CONCLUSION In segmented GB,discordance in the filling patterns detected by HBS and anatomical imaging could lead to misinterpretation of GBEF.For this reason,clinicians should be cautious when interpreting HBS results in patients with segmented GB.

Importance of proper ventilator support and pulmonary rehabilitation in obese patients with heart failure:Two case reports

BACKGROUND The optimal treatment for heart failure(HF)is a combination of appropriate medications.Controlling the disease using only medical therapy is difficult in patients with HF,severe hypercapnia,and desaturation.These patients should first receive ventilator support followed by pulmonary rehabilitation(PR).CASE SUMMARY We report two cases in which arterial blood gas(ABG)improved and PR was possible with appropriate ventilator support.Two patients with extreme obesity complaining of worsening dyspnea–a 47-year-old woman and a 36-year-old man both diagnosed with HF–were hospitalized because of severe hypercapnia and hypoxia.Despite proper medical treatment,hypercapnia and desaturation resolved in neither case,and both patients were transferred to the rehabilitation department for PR.At the time of the first consultation,the patients were bedridden because of dyspnea.Oxygen demand was successfully reduced once noninvasive ventilation was initiated.As the patients’dyspnea gradually improved to the point where they could be weaned off the ventilator during the daytime,they started engaging in functional training and aerobic exercise.After 4 mo of followup,both patients were able to perform activities of daily living and maintain their lower body weight and normalized ABG levels.CONCLUSION Symptoms of patients with obesity and HF may improve once ABG levels are normalized through ventilator support and implementation of PR.

Real-Time Remote-Mentored Echocardiography in Management of Newborns with Critical Congenital Heart Defects

Background:The management of suspected critical congenital heart defects(CCHD)relies on timely echocardiographic diagnosis.The availability of experienced echocardiographers is limited or even non-existent in many hospitals with obstetric units.This study evaluates remote-mentored echocardiography performed by physicians without experience in imaging of congenital heart defects(CHD).Methods:The setup included a pediatric cardiologist in a separate room,guiding a physician without experience in echocardiographic imaging of CHD in the examination of a symptomatic newborn.This remote-mentoring pair was blinded to the diagnosis of the newborn and presented with a simplified patient history.The echocardiographic images were streamed to the laptop of the mentor,along with a webcam feed showing the probe position.The task was to identify CCHD in need of immediate transfer to a pediatric cardiac surgical center.The result was compared to the previously completed echocardiographic report and the clinical decision of the patient-responsible pediatric cardiologist.Results:During 17 months,15 newborns were recruited.All six newborns with CCHD were correctly labeled by the remotementoring pair.One newborn with Tetralogy of Fallot was erroneously labeled as needing immediate transfer.Eight newborns without CCHD were correctly labeled.Conclusions:Remote-mentored echocardiography performed by examiners without experience in imaging CHD identified all newborns with CCHD in need of immediate transfer for specialist care.The setup shows promising results for improving the management of CCHD in hospitals without continuous pediatric cardiology service.

Diagnostic use of superb microvascular imaging in evaluating septic arthritis of the manubriosternal joint:A case report

BACKGROUND Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical characteristic.Conventional ultrasound,plain radiographs,and computed tomography are not able to confirm or even suspect arthritis early.Superb microvascular imaging is a new advanced Doppler technique in evaluating low-flow microvascular patterns.The higher sensitivity for increased perisynovial vascularity helps to suspect septic arthritis and forms a methodical approach to using magnetic resonance imaging(MRI).CASE SUMMARY A 34-year-old immunocompetent woman presented with a fever and a dull ache in the chest radiating to the right arm.Traumatic injury and the most common respiratory and cardiac disorders were ruled out.Blood cultures came back positive for Staphylococcus aureus,and sepsis was confirmed.A small lump was noted on the chest during the first week of hospitalization.Superb microvascular imaging was performed and septic arthritis of the manubriosternal joint was detected.MRI confirmed the diagnosis and showed septic arthritis of the manubriosternal joint with several localized abscesses behind the sternum.The patient was treated for three weeks with intravenous antibiotics and the outcome was favorable:Inflammatory markers became normal,and the lump disappeared.Three months later,the patient was examined for a new episode of mild pain in the sternum and was diagnosed with persistent perichondritis by ultrasound in comparison with MRI.CONCLUSION Superb microvascular imaging is a useful tool for the early diagnosis of septic arthritis of the manubriosternal joint and following-up.

Network pharmacology and preliminary cell screening studies on the anti-liver cancer activity of Nauclea Officinalis

Objective:To explore the mechanism of Nauclea Officinalis of anti-liver cancer effect based on network pharmacology,and to preliminarily verify anti-liver cancer activity of Nauclea Officinalis through cell screening.Methods:Network pharmacology was used to screen for common targets of Nauclea Officinalis and liver cancer,protein-protein interaction(PPI)network was constructed,and enrichment analysis and mechanism prediction were conductd.Molecular docking of main active ingredients of Nauclea Officinalis with core targets was made.Preliminary verification was performed by in vitro cell experiments such as CCK8,cell apoptosis,and PCR.Results:After the screening,14 active ingredients of Nauclea Officinalis were obtained,with 587 related targets.After mapping with liver cancer targets,there were 288 common targets,mainly including TP53,SRC,STAT3,and other core targets.Among them,compounds such as strictosamide,pumiloside and vincosamide may be potential active ingredients of Nauclea Officinalis of anti-liver cancer effect.They may participate in protein phosphorylation and negative regulation of the apoptosis process by mediating cancer pathways,PI3K/Akt and EGFR tyrosine kinase inhibitors resistance signaling pathways to play an anti-liver cancer role;molecular docking results showd that active ingredients of Nauclea Officinalis had a stable binding with liver cancer core targets;in vitro cell experiments showd that main ingredient strictosamide of Nauclea Officinalis had cytotoxicity against liver cancer cells,inhibited liver cancer cell proliferation(P<0.001),down-regulated gene expression of liver cancer HepG2 cells SRC,STAT3,MAPK3(P<0.05),and induced liver cancer cell apoptosis(P<0.001).Conclusion:This study preliminarily explores the potential mechanism of active ingredients of Nauclea Officinalis against liver cancer and its preliminary pharmacological effects,providing a theoretical basis for the study of Nauclea Officinalis of anti-liver cancer mechanism.