AIM:To evaluate the clinical efficacy of lamellar keratectomy and corneal collagen crosslinking(LKCCC)in treating superficial fungal keratitis.METHODS: Retrospective analysis. Totally 79 patients(79 eyes)with superficial fungal keratitis who underwent LKCCC in our hospital from January 2014 to October 2023 were included. After admission, routine antifungal drug treatment for 7 d showed no obvious improvement or progressive aggravation. The maximum diameter of corneal lesions in all patients was ≤7 mm, the maximum depth was no more than 50% of the corneal thickness at the location, and the remaining healthy corneal thickness was ≥300 μm. The follow-up time was 90 to 112 d.RESULTS:Among the included 79 eyes, the lesions were located in the central region of the cornea in 6 eyes, in the paracentral region in 61 eyes, and in the peripheral region in 12 eyes. Hypopyon was observed in 5 cases. LKCCC was successfully administered in 79 eyes, cured in 76 eyes(96%), and failed in 3 eyes(4%). The healing time of corneal epithelium in 76 cured eyes was 3-15 d, of which 51 eyes(67%)healed within 7 d and 24 eyes(32%)healed within 3 d. The uncorrected visual acuity(UCVA)and best corrected visual acuity(BCVA)of 76 eyes of cured patients were statistically significant compared with those preoperatively(P<0.0167). Two of the 3 failed eyes were located at the edge of the lesion and recovered after re-keratectomy. One eye was located in the center of the lesion and recovered after being covered by bulbar conjunctival flap. At the last follow-up, no other complications were observed in all patients except superficial cloud and thinning of cornea.CONCLUSION:LKCCC is a rapid and effective treatment for superficial fungal keratitis and can be considered a new treatment option.

AIM: To assess the impact of optimized pulsed technology(OPT)on the morphological and functional changes of meibomian glands in patients with meibomian gland dysfunction(MGD).METHODS: This prospective case-control study enrolled 60 MGD patients(60 right eyes)treated at Weifang Eye Hospital from September 2023 to February 2024. Patients were categorized into mild, moderate, and severe groups based on the extent of meibomian gland loss, with 20 cases(20 eyes)per group. Treatments consisted of bilateral OPT combined with meibomian gland massages, administered biweekly over four sessions. Ocular surface function indicators including the ocular surface disease index(OSDI), corneal fluorescein staining(CFS), non-invasive average tear break-up time(NIBUTav), and non-invasive tear meniscus height(NITMH), as well as meibomian gland function parameters such as meibomian gland expressibility score(MGES)and meibomian gland secretion score(MGYSS)were observed and recorded before treatment and at 3 mo after final treatment. Cellular-level assessments using in vivo confocal microscopy(IVCM)examined meibomian gland acinar unit density(MGAUD), inflammatory cell density(ICD), meibomian gland acinar longest diameter(MGALD)and meibomian gland acinar shortest diameter(MGASD).RESULTS: At baseline, no significant differences were found in NITMH across groups(P>0.05). Statistical significance were observed in NIBUTav, MGES, MGYSS, MGAUD, MGALD, and MGASD(all P<0.05). Compared to the mild group, the moderate and severe groups showed significant differences in OSDI, CFS, and ICD(all P<0.05), though no significant differences existed between moderate and severe groups(all P>0.05). At 3 mo after treatment, all groups showed no significant differences in NITMH(all P>0.05). All parameters improved significantly in the mild group(all P<0.05); all indicators improved in the moderate group(P>0.05), except for MGASD before and after treatment(all P<0.05); significant improvements were noted in OSDI, CFS, and NIBUTav in the severe group(all P<0.05), while MGES and MGYSS did not differ significantly(all P>0.05). IVCM parameters(MGAUD, ICD, MGALD, and MGASD)showed no significant change in the severe group(all P>0.05).CONCLUSION:OPT effectively enhances various ocular surface functions and improves gland expressibility and secretion quality in mild to moderate MGD cases, while also positively impacting certain cellular parameters. In severe cases, where most acinar functions are lost and structural reversibility is limited, OPT can still mitigate MGD symptoms and decelerate disease progression.

Amide bond is formed by dehydration and condensation of amino and carboxyl groups in a molecule, which is used in structural design of drugs. The stability of the amide bond is affected by many factors, which make the pharmacokinetic behaviors of amide drugs complicated by metabolic heterogeneity. This review proposes that the expression and activity of hydrolase may be one of the important reasons for the obvious differences in the pharmacokinetics of amides among species, summarizes the common metabolic enzymes or proteins responsible for hydrolyzing amides so as to provide some reference for the structural design and further clinical study of amide drugs, and suggests that improper selection of in vitro evaluation systems may be an important cause for the inconsistency between between in vitro and in vivo pharmacokinetic characteristics of drugs, with a summary of the currently used in vitro drug metabolism systems for drug evaluation, aiming to provide a basis for preclinical evaluation of drugs.

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged

Background and purpose:Approximately 30%of patients with metastatic colorectal cancer(CRC)develops pulmonary metastasis,yet less than 10%are eligible for surgical resection.Radiofrequency ablation(RFA)serves as an alternative therapy for non-surgical candidates,but the relationship between its efficacy and tumor diameter remains controversial.This study aimed to investigate the impact of tumor size on survival outcomes and local progression risk in CRC patients with pulmonary metastasis after RFA,and to validate the clinical utility of a 3 cm threshold for prognosis.Methods:This retrospective study included CRC patients with pulmonary metastasis who underwent RFA at Fudan University Shanghai Cancer Center between January 2016 and December 2024.Patients were stratified into two groups based on maximum lesion diameter:≤3 cm(Small group)and 3-5 cm(Large group).Patient inclusion criteria:⑴ pathologically confirmed lung metastases originating from CRC,with metastases limited to the lungs or extra-pulmonary metastatic lesions having been radically treated;⑵ maximum lesion diameter<5 cm;⑶complete clinical data available;⑷ complete imaging data available,including computed tomography(CT)images during ablation and contrast-enhanced CT images during postoperative follow-up;⑸ follow-up time of at least＞6 months after RFA;⑹ technical complete ablation;⑺ fewer than 3 pulmonary metastatic lesions.Exclusion criteria:⑴ target lesions previously treated with local therapies such as RFA or radiotherapy;⑵ patients unable to tolerate RFA;⑶ patients with follow-up time＜6 months after RFA.Three senior interventional physicians performed percutaneous RFA under guidance of a 64-slice spiral CT scanner.Chest contrast-enhanced CT scans obtained 1 month after RFA were used as the baseline,followed by contrast-enhanced CT scans every 3 months for 1 year,then every 6 months for subsequent follow-up.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical approval number:2108241-11).Primary endpoints included overall survival(OS),progression-free survival(PFS),and local tumor progression(LTP).Kaplan-Meier analysis and multivariate COX regression were employed to evaluate the independent prognostic value of tumor size.Results:A total of 134 patients who met the inclusion criteria were ultimately enrolled,including 77 in the Small group and 57 in the Large group.With a median follow-up of 35 months,the≤3 cm group demonstrated superior 1-,3-,and 5-year OS rates(100.0%,95.1%,74.2%)compared to the 3-5 cm group(94.7%,36.8%,27.0%,P＜0.0001),and the≤3 cm group demonstrated superior 1-,3-,and 5-year PFS rates(90.9%,34.4%,23.3%)compared to the 3-5 cm group(13.8%,0.0%,0.0%,P＜0.000 1).The≤3 cm group also exhibited significantly lower 1-,3-,and 5-year LTP rates(0.0%,19.7%,33.6%)compared to the 3-5 cm group(46.0%,75.5%,75.5%,P＜0.000 1).Multivariable analysis identified tumor diameter＞3 cm as an independent predictor of worse OS[hazard ratio(HR)=6.49,95%CI:3.18-13.24,P＜0.001],while elevated preoperative carcinoembryonic antigen(CEA)(≥5 ng/mL)correlated with shorter OS(HR=1.82,P=0.033).Conclusion:CRC patients with pulmonary metastasis and tumor diameters of 3-5 cm exhibited significantly inferior survival outcomes after RFA compared to the≤3 cm group.A tumor diameter of 3 cm can serve as a critical threshold for selecting RFA indications,and combining preoperative CEA levels can optimize patient stratification.

Purpose To investigate the impact of patient positioning deviation on CT image quality and radiation dose in chest CT scans.Materials and Methods A retrospective analysis was conducted on all patients who underwent chest high-resolution CT plain scans from January 22 to 26,2024,at the Second Affiliated Hospital,Zhejiang University School of Medicine.The distance between the gantry center and patient center was measured.Patients were divided into three groups based on the magnitude of deviation from the isocenter:negative deviation group,isocenter group and positive deviation group.Compared the signal to noise ratio(SNR),CT dose index volume(CTDIvol),dose length product(DLP)and SNR/CTDI distribution among the three patient groups.Results Among the 965 patients studied,29.95%(289 cases)were accurately positioned,while 70.05%(676 cases)deviated from the center.The frequency of positive deviation(31.81%,307/965)was lower than that of negative deviation(38.24%,369/965).Compared with the isocenter group,patients in the negative deviation group received higher CTDIvol and DLP but superior SNR,while those in the positive deviation group received lower CTDIvol and DLP with inferior SNR(H=213.783,187.595,59.247,all P<0.05).The SNR/CTDI ratio in the isocenter group 0.84(0.50)was significantly higher than that in the negative deviation group 0.72(0.54)and the positive deviation group 0.71(0.38)(H=13.257,P<0.05).There was a significant association between gender and deviation direction.Patients with higher body weight and taller stature,particularly male patients,demonstrated negative deviation,while those with lower body weight and shorter stature tended to positive deviation.Conclusion Accurate positioning in chest CT scans can ensure diagnostic accuracy while minimizing radiation exposure and achieving the best image quality-to-radiation dose ratio.However,as a population-based preliminary study,the findings should be complemented by phantom experiments to further validate the correlation between anthropometric parameters and positional deviations in clinical CT practice.

Objective:To investigate the clinical effect of the transfer of lateral femoral fascia or combined with anteriolateral thigh flap (ALTF) on treatment of defects of Achilles tendon and surrounding soft tissue.Methods:From May 2004 to December 2021, 15 patients with Achilles tendons defects were treated with the transfer of either lateral femoral fascia or combined with ALTF in the Department of Hand and Foot Microsurgery, Xi'an Fengcheng Hospital. Two of the patients had postoperative infection after the primary treatment for Achilles tendon rupture and 13 patients had Achilles tendon defect together with various grade of defects of surrounding soft tissues. According to the size of wound, ALTFs and lateral superior knee flaps were used for the reconstructions. Various complex tissue flaps were used in reconstructive surgery: ALTF in 10 patients, the lateral thigh muscular flap in 3 patients and the lateral knee artery flap in 5 patients. The length of Achilles tendon defect was 3.0-8.0 cm and the length of fascia was 4.0-9.0 cm. The sizes of the flaps were 4.0 cm×3.0 cm-30.0 cm×18.0 cm. After the fascia and the flaps were harvested, the fascia was rolled up or wrapped up around the muscle with the knee at 30° flexion and the ankle at 30° flexion. Then end-to-end or end-to-side blood vessel anastomoses were carried out. The ALTFs were used to cover the wounds.Results:All the 15 flaps survived. After 2 to 5 years of follow-up, the heel lift test was found negative, without re-broken of Achilles tendon. All patients were in normal walking gait, except 2 patients who had mild lameness. According to the Amer-Lindholm scoring criteria, the results were excellent in 13 patients and good in 2 patients.Conclusion:Lateral thigh composite tissue transfer is an effective method to reconstruct Achilles tendon and the defects of its surrounding tissues.

Objective:To investigate intraoperative pathological findings and the interventional effects of "deep cervical lymphaticovenous anastomosis+" (dcLVA+) on deep cervical lymphatic drainage as well as the blood flow of carotid artery and jugular vein in elderly patients with cognitive impairment, and to put forward the thoughts based on the findings from the surgery.Methods:Between May 2024 and December 2024, retrospective analysis of Microsurgery Hospital, Fengcheng Hospital, Xi'an Medical College performed dcLVA+ between the deep cervical lymphatics or lymph nodes and jugular veins in 50 elderly patients with cognitive impairment (19 males and 31 females, aged 55-88 years with 69.94 years in average). Nine patients were found with Clinical Dementia Rating (CDR) score at 1 (mild), 7 with CDR score at 2 (moderate) and 34 with CDR score at 3 (severe). Intraoperative observations based on literature reviews had identified anatomical relationships between the lymphatic sacs containing cervical lymphatic chain and the carotid sheath. The lymph node count, size, distribution, thickness of fat tissue and conditions of lymphatic vessels were documented. Ultrasound was used to compare the blood flow of carotid artery and jugular vein as well as the cross-sectional areas at the planes of hyoid and cricoid cartilage before and after the closure of incisions under anaesthesia in 39 patients. Correlation analyses for Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCa), Activities of Daily Living (ADL) and Agitation behavior score before and 1 week after surgery were performed using Spearman's correlation and Wilcoxon paired tests. P<0.05 was considered statistically significant. Postoperative follow-ups were conducted via the visit of outpatient clinic and WeChat and telephone interviews. Results:In surgery, the cervical lymphatic chain was found running within an almost enclosed sac surrounding the carotid sheath. There were enlarged lymph nodes, increased fat deposition, lymphatic dilation or fibrosis in the sac. The preoperative blood flow in the carotid artery at the planes of hyoid and cricoid cartilage in the 39 patients was recorded at 150.52 ml/min±40.33 ml/min and 358.29 ml/min±129.30 ml/min, while that in the jugular vein was at 172.50 ml/min±63.94 ml/min and 317.00 ml/min±105.21 ml/min, respectively, both were far lower than the normal blood flow. There were statistically significant differences in the blood flow of carotid artery and jugular vein before and after surgery ( P<0.01). It was found that the preoperative blood flow of the internal carotid artery at the plane of hyoid was positively correlated with the preoperative scores of MMSE ( P<0.01), MoCa ( P<0.05) and ADL ( P<0.01). The blood flow of the common carotid artery at the plane of cricoid cartilage was found significantly and positively correlated with the preoperative scores of MMSE ( P<0.05). It was also noted that the blood flow of the internal carotid artery at the plane of hyoid was significantly and positively correlated with the postoperative ADL ( P<0.01) but negatively correlated with the Agitation behavior score ( P<0.05). The blood flow of the common carotid artery at the plane of cricoid cartilage was significantly and positively correlated with the postoperative scores of MMSE and MoCa ( P<0.05). The blood flow of the internal jugular vein at the plane of hyoid was negatively correlated with the Agitation behavior score ( P<0.01). The cross-sectional area of carotid artery at the plane of left hyoid was significantly and positively correlated with the MMSE score ( P<0.05). Statistically significant differences were observed in MMSE, MoCa, ADL and Agitation behavior score before and after surgery ( P<0.01). Conclusion:dcLVA+ shows a certain therapeutic benefit to the elderly patients with cognitive impairment. The intraoperatively observed pathological changes in cervical lymphatic sacs affect deep cervical lymphatic drainage and the blood flow of carotid artery and jugular vein. Further studies are necessary to find out whether the findings from this study would be the specific pathological changes and the morbidity mechanisms among the elderly patients with cognitive impairment.

Objective To investigate the prognostic value of thrombin-antithrombin III complex(TAT),plasmin-α2-plasmin inhibitor complex(PIC),thrombomodulin(TM)and tissue plasminogen activator-inhibitor complex(t-PAIC)in patients with myelodysplastic syndrome(MDS).Methods Selected 88 primary MDS patients diagnosed at the 521 Hospital of Ordnance Industry from January 2018 to January 2021.Plasma levels of TAT,PIC,TM,t-PAIC,fibrin degradation products(FDP)and D-dimer(D-D)were measured.A multivariate approach was used to analyze the association between overall survival(OS)and the levels of each coagulation marker.Coagulation markers significantly associated with OS were used to construct a coagulation prognostic scoring system.Based on the median coagulation marker score,MDS patients were divided into high and low score groups.Kaplan-Meier analysis was used to plot survival curves.Results TAT(OR=1.667),PIC(OR=0.734),TM(OR=1.294)and t-PAIC(OR=1.523)were independent factors influencing OS in MDS patients(Wald χ2=0.671～10.751,all P<0.05).The β-values were integrated as statistical weights to construct a coagulation marker score,calculated as follows:[TAT]×0.502-[PIC]×1.013+[TM]×0.181+[t-PAIC]×0.381.The OS(median 14.6 months)and leukemia free survival(LFS)(median 10.3 months)of patients in the high coagulation marker score group were significantly lower than those in the low score group(33.6 months,35.2 months)(Log rank=20.57,26.84,all P<0.001).Subgroup analysis indicated that in both the low-risk IPSS-R subgroup(very low,low,and intermediate risk)and the high-risk IPSS-R subgroup(high and very high risk),the OS(Log rank=9.12,4.30)and LFS(Log rank=4.54,8.51)of the high coagulation marker score group were lower than those of the low score group(all P<0.05).Bivariate analysis showed a moderate correlation between the coagulation marker score and Revise International Prognostic Scoring System(IPSS-R)(PCC=0.536,P<0.001).Multivariate analysis indicated that IPSS-R and high coagulation marker scores were independent risk factors for OS and LFS in MDS patients(P<0.05).Conclusion The coagulation marker score,based on TAT,PIC,TM and t-PAIC,can serve as an independent prognostic factor for OS and LFS in MDS patients.

Objective To investigate the impact of enterovirus 71(EV71)on skeletal muscle injury and explore its mechanism in relation to the caspase-1/interleukin(IL)-1 β signaling pathway in EV71-induced skeletal muscle damage.Methods One-day-old BALB/c suckling mice were divided randomly into three groups:normal control(NC)(n=60),EV71 infection model(n=60),and caspase-1 inhibitor(EV71+VX765)(n=15)groups.The NC and EV71 model groups were further subdivided into four subgroups(5,7,10,and 14 days)(n=5 mice per group).An EV71-infected model was established by intraperitoneal injection of 25 × 103 μL/kg EV71 viral solution for 3 consecutive days.Mice in the caspase-1 inhibitor group received VX765(20 mg/kg)intraperitoneally 6 hours post-viral inoculation,continued daily for 10 days until sample collection.Mice in the NC group received an equivalent volume of saline containing 5％dimethylsulfoxide and 10％PEG300,followed by 2％cell maintenance solution after 6 hours.Post-modeling body weight and clinical disease scores were recorded.Pathological skeletal muscle damage was observed by hematoxylin-eosin(HE)staining,and expression levels of EV71 VP-1(viral capsid protein),pro-caspase-1,cleaved-caspase-1,IL-1 β,α-smooth muscle actin(SMA),and Collagen Ⅰ were detected by Western blot and immunofluorescence.Results Compared with the NC group at the same time points,mice in the EV71 model group exhibited reduced body weight,elevated disease scores,and skeletal muscle pathology characterized by inflammatory cell infiltration,myofiber dissolution,and decreased cross-sectional area(HE staining).Western blot showed significantly increased levels of EV71 VP-1,IL-1β,α-SMA,and Collagen Ⅰ in skeletal muscle homogenate from EV71 mice at 5,7,and 10 days post-infection(P＜0.001).In contrast,mice in the VX765 group showed improved body weight,reduced clinical scores(P＜0.01),and significant downregulation of EV71 VP-1(P＜0.01),pro-caspase-1,cleaved-caspase-1,IL-1β,and Collagen Ⅰ compared with the EV71 model group(P＜0.01).These findings were confirmed by immunofluorescence,indicating that inhibition of caspase-1 alleviated EV71-induced skeletal muscle injury.Conclusions EV71 may induce skeletal muscle injury by activating the caspase-1/IL-1β signaling pathway.