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.

ObjectiveThis study aims to examine the effect of Rhei Radix et Rhizoma-Coptidis Rhizoma on reducing insulin resistance in db/db mice by regulating the adenylate activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1）/key molecule of autophagy， benzyl chloride 1 （Beclin1） pathway and elucidate the underlying mechanism. MethodSixty 6-week-old male db/db mice were studied. They were randomly divided into the model group， metformin group （0.26 g·kg^-1）， and low-， middle-， and high-dose groups （2.25， 4.5， 9 g·kg^-1） of Rhei Radix et Rhizoma-Coptidis Rhizoma. A blank group of db/m mice of the same age was set， with 12 mice in each group. After eight weeks of continuous intragastric administration， the blank group and model group received distilled water intragastrically once a day. The survival status of the mice was observed， and fasting blood glucose （FBG） was measured using a Roche blood glucose device. Fasting serum insulin （FINS） was measured using an enzyme-linked immunosorbent assay， and the insulin resistance index （HOMA-IR） was calculated. Hematoxylin-eosin （HE） staining was performed to observe the pathological changes in the liver of the mice. The protein expression levels of AMPK， Beclin1， autophagy associated protein 5 （Atg5）， and p62 in liver tissue were determined by using Western blot. The protein expression levels of autophagy associated protein 1 light chain 3B （LC3B） and ULK1 in liver tissue were determined using immunofluorescence. Real-time fluorescence quantitative PCR （Real-time PCR） was used to measure mRNA expression levels of AMPK， Beclin1， Atg5， ULK1， and p62. ResultCompared with the blank group， the model group exhibited a significant increase in body mass （P<0.01）. Additionally， the levels of FBG， FINS， and HOMA-IR significantly changed （P<0.01）. The structure of liver cells was disordered. The protein expression levels of AMPK， Beclin1， and Atg5 in liver tissue were significantly decreased （P<0.01）， while the expression level of p62 protein was significantly increased （P<0.01）. The expression levels of mRNA and proteins were consistent. Compared with the model group， the body mass of the metformin group and high and medium-dose groups of Rhei Radix et Rhizoma-Coptidis Rhizoma was significantly decreased （P<0.05）. FBG， FINS， and HOMA-IR were significantly decreased （P<0.05，P<0.01）. After treatment， the liver structure damage in each group was alleviated to varying degrees. The protein expressions of AMPK， Beclin1， Atg5， LC3B， and ULK1 were increased （P<0.05，P<0.01）， while the protein expression of p62 was decreased （P<0.01）. The expression levels of mRNA and proteins were generally consistent. ConclusionThe combination of Rhei Radix et Rhizoma-Coptidis Rhizoma can effectively improve liver insulin resistance， regulate the AMPK autophagy signaling pathway， alleviate insulin resistance in db/db mice， and effectively prevent the occurrence and development of type 2 diabetes.

Objective To investigate the clinical efficacy of transurethral plasma electrotomy with rod electrode and end-to-end urethral anastomosis in the treatment of short urethral stricture.Methods 125 male patients with short urethral stricture(＜2 cm)who were admitted to our hospital from January 2014 to December 2020 were retrospectively analyzed.According to different surgical methods,they were divided into transurethral plasma resection with rod electrode(minimally invasive group)and urethral end-to-end anastomosis(open group).According to the length of urethral stricture,the minimally invasive group was divided into minimally invasive group 1(stricture length≤1 cm),minimally invasive group 2(stricture length1-2 cm),open group 1(stricture length ≤1 cm)and open group 2(stricture length 1-2 cm).The four groups were compared with each other,and the surgical success rates were compared between the four groups.Results The success rate of the minimally invasive group 1 and the open group 1 was 88.57％and 93.10％,respectively.There was no significant difference between the two groups(P＞0.05).The surgical success rate of the minimally invasive group 2 and the open group 2 was 67.86％and 90.91％,respectively.The surgical success rate of the minimally invasive group 2 was significantly lower than that of the open group 2.The difference was statistically significant(P＜0.05).The surgical success rate of minimally invasive group 1 and minimally invasive group 2 was 88.57％and 67.86％,respectively,the difference was statistically significant(P＜0.05).The success rate of operation in the open group 1 and the open group 2 was 93.10％and 90.91％,respectively,and there was no significant difference between the two groups(P＞0.05).Conclusion Transurethral plasma resection with rod electrode is preferred for urethral stricture with length≤1 cm,because the success rate of this surgery is the same as that of open surgery,and the surgical trauma is small and the recovery is fast.For 1-2 cm urethral stricture,minimally invasive surgery has less trauma and faster recovery,but open surgery has a higher success rate.The choice of surgical method needs to weigh the advantages and disadvantages and take comprehensive consideration.

Objective:To explore the genetic etiology for a patient with Alstr?m syndrome (ALMS) presenting as dilated cardiomyopathy.Methods:A 41-year-old male patient who had presented at the Sixth Medical Center of PLA General Hospital on October 20, 2021 was selected as the study subject. Clinical and laboratory examinations were carried out. Whole exome sequencing (WES) was employed for genetic testing, and candidate variants were validated by Sanger sequencing and pathogenicity analysis.Results:The patient had a 14-year medical history characterized by dilated cardiomyopathy, complete atrioventricular block, visual impairment, sensorineural hearing loss, truncal obesity, insulin resistance, type 2 diabetes, hypertension, renal dysfunction, and paranoid delusions. Genetic testing revealed that he has harbored compound heterozygous variants of the ALMS1 gene, namely c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2). Sanger sequencing confirmed that they were inherited from his father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1_VeryStrong+ PM2_Supporting+ PM3+ PP3, PVS1_VeryStrong+ PM2_Supporting+ PM3). Literature review indicated that the complete atrioventricular block in the patient was a phenotype unreported previously. Conclusion:The c. 6823C>T (p.Arg2275Ter) and c. 9442_9445dup (p.Ser3149LysfsTer2) compound heterozygous variants of the ALMS1 gene probably underlay the pathogenesis in this patient. Above findings have expanded the phenotypic spectrum of ALMS and provided insights for clinicians dealing with similar cases.

Objective:To construct a risk model of liver injury related to parenteral nutrition (PNALD) in patients with severe acute pancreatitis (SAP).Methods:The clinical data of 176 SAP patients admitted to the 971 Hospital of Navy from January 2019 to August 2021 were retrospectively collected. According to whether PNALD occurred or not, the patients were divided into liver injury group ( n=33) and non-liver injury group ( n=143). Multivariate logistic regression was used to analyze the influencing factors of PNALD in SAP patients. Then decision tree model and multivariate logistic regression model were established based on the screened risk factors. Hosmer and Lemeshow Test calibration curves were used to calibrate the two models, and receiver operating characteristic curve (ROC) was drawn and area under the curve (AUC) was calculated to compare the prediction efficiency of the two models. Results:Drinking history (history of alcohol intake), serum albumin / globulin ratio ≤1.45, prothrombin time (PT)≥18.52 s, PT activity ≤48.96, activated partial thromboplastin time (APTT) ≥45.91 s were all risk factors for PNALD. The ROC curve of the multivariate logistic regression model and the decision tree model was drawn, and calculated AUC of the two models was 0.851 and 0.906, respectively; the sensitivity was 79.6% and 80.8%, respectively; the specificity was 80.5% and 79.6%, respectively; and the Youden index was 0.601 and 0.604, respectively, with good consistency.Conclusions:Low serum albumin/globulin ratio and PT activity, high PT and APTT are all risk factors for PNALD. The PNALD prediction model based on the above risk factors has high specificity and sensitivity.

Objective To summarize experience of anti-cancer drug management for clinical trials,and to explore a more efficient and standardized management model of anti-cancer drugs used in clinical trials.Methods Based on our current work in central pharmacy,the particularity and complexity of anti-cancer drug management for clinical trials were analyzed.In the meantime,we identified high-risk parts in the drug management process.Based on those risks,feasible measures were taken and presented in detail.Results Management of anti-cancer drugs used in clinical trials has its characteristics,such as long cycle,low error-tolerant rate,closed-loop model,etc.Recognizing these representative high-risk parts during the trials and making responses,including standardization of drug management records and disposition of drugs and packaging returned by subjects,should be achieved as soon as possible.Conclusion Establishing and observing strict rules and regulations,improving the hardware and software performance of the central pharmacy as well as implementing risk-based drug management is beneficial to conduct clinical trials normatively.

Objective:To assess the clinical efficacy and safety of image-guided γ-ray stereotactic body radiation therapy(IG γ-SBRT)in treating advanced pancreatic cancer.Methods:A total of fifty-six patients with advanced pancreatic cancer admitted to Senior Department of Oncology Medicine of the Fifth Medical Center of Chinese PLA General Hospital(Department of Oncology of the Sixth Medical Center)from February 2017 to September 2020 were selected.All patients were treated with IG γ-SBRT,and the 50%-60%of isodose curve covered the planned target volume(PTV).The peripheral dose of each time was 3.0-4.5 Gy,and there were 10-11 times of treatment.The therapeutic effect was observed and was evaluated by follow-up.The visual analog scale(VAS)score was adopted to assess the situation of the pain of patients before and 3 months after treatment,and the adverse reaction of them.Results:In the 56 patients,52 cases occurred epigastric pain with VAS ranging from 3 to 10 points,among which 32 patients accompanied by symptoms such as lower back pain and abdominal distension.After 3 months of treatment,the results of reexamination and follow-up indicated that there were 48 patients whose VAS scores decreased 3 scores and above 3 scores on the basis of original scores,and the efficiency of treating pain was 92.3%.In addition,the VAS scores of 3 patients decreased 1-2 scores on the basis of original scores,which ratio was 5.85%of the total number of people.All 56 patients were reexamined at the 3rd month after treatment,and 13 cases of them obtained complete response(CR),and 37 cases obtained partial response(PR),and 1 case obtained progressive disease(PD),and 5 cases obtained stable disease(SD),and the objectively response rate(ORR)was 89.3%,and the locally control rate was 98.2%.In addition,median progression-free survival(PFS)was 6.5 months,and 1-year survival rate was 62.5%(35/56),and 2-year survival rate was 23.2%(13/56).The adverse reactions of 56 patients were the adverse reactions of digestive system and blood system,among which 47 patients occurred upper digestive tract reaction,and the incidence of adverse reactions was 83.9%(47/56).A total of 43 patients occurred myelosuppression,and the incidence of myelosuppression was 76.8%(43/56).Conclusion:IG γ-SBRT can effectively relieve the symptoms of metastatic pancreatic cancer,and improve the effectiveness of treatment,the local control rate and survival rate.The tolerance of adverse reaction of that is favorable,and the safety of that is higher.

Objective:To analyze the optimal dose of urokinase (UK) for intravenous thrombolysis in Chinese patients with acute ischemic stroke within 4.5 hours of onset.Methods:Based on the intravenous thrombolysis registry for Chinese ischemic stroke within 4.5 hours of onset (INTRECIS) cohort, consecutive patients who received intravenous UK from April 1, 2017 to July 1,2019 were retrospectively collected . According to the tertile dose of UK per body weight, eligible patients were divided into low dose group [(1.00-1.67)×10 4 international unit per kilogram], moderate dose group [(1.68-2.33)×10 4 international unit per kilogram] and high dose group (2.34-3.00)×10 4 international unit per kilogram]. Furthermore, subgroups were analyzed according to age, gender, and baseline National Institutes of Health Stroke Scale (NIHSS) scores. The primary efficacy outcome was excellent functional outcome, defined as a 90-day modified Rankin Scale (mRS) score of 0-1. The secondary efficacy outcomes included favorable functional outcome (mRS score of 0-2 at 90 days), mRS score distribution at 90 days and changes in NIHSS score at 1 day and 14 days, compared with the baseline. The primary safety outcome was symptomatic intracranial hemorrhage (sICH), and the secondary safety outcomes included recurrence of stroke within 90 days, all-cause mortality and any random bleeding events. Results:A total of 1 144 patients were included in the analysis: 549 in the low dose group, 509 in the moderate dose group and 86 in the high dose group. The proportion of excellent functional outcome was higher in the high dose group, compared with the low dose group [79.07% (68/86) vs 67.03% (368/549), OR=2.427, 95% CI 1.280-4.587, P=0.007] and the moderate dose group [79.07%(68/86) vs 70.53%(359/509), OR=1.942, 95% CI 1.023-3.690, P=0.043]. The incidence of sICH was similar among the 3 groups [high dose group vs low dose group: 1.16% (1/86) vs 2.00% (11/549), OR=0.607, 95% CI 0.071-5.153, P=0.648; high dose group vs moderate dose group: 1.16%(1/86) vs 0.79% (4/509), OR=0.330, 95% CI 0.101-1.074, P=0.596]. The subgroup analysis showed that higher proportion of excellent functional outcome was found in the high dose group patients with senior citizens (≥60 years old) [high dose group vs low dose group: 80.70% (46/57) vs 63.07% (222/352), OR=3.401, 95% CI 1.500-7.752, P=0.003; high dose group vs moderate dose group: 80.70% (46/57) vs 69.63% (227/326), OR=2.381, 95% CI 1.074-5.291, P=0.033], moderate neurologic deficit (NIHSS score 4-16) [high dose group vs low dose group:79.07% (34/43) vs 62.61% (211/337), OR=2.604, 95% CI 1.190-5.682, P=0.017; high dose group vs moderate dose group:79.07% (34/43) vs 65.02% (184/283), OR=2.315, 95% CI 1.055-5.097, P=0.036], and large artery atherosclerosis [high dose group vs low dose group: 81.40% (35/43) vs 62.32% (177/284), OR=3.584, 95% CI 1.416-9.009, P=0.007; high dose group vs moderate dose group: 81.40% (35/43) vs 66.06% (144/218), OR=2.793, 95% CI 1.090-7.143, P=0.032]. Conclusions:Intravenous UK dose calculated according to body weight may be reasonable for treating acute ischemic stroke. Intravenous UK with dose of (2.34-3.00)×10 4 international unit per kilogram may favor better benefit for acute ischemic stroke, which warrants further confirmation.

Objective:To investigate distinct trahectories of demoralization of maintenance hemodialysis patients in young and middle-aged adults, and analyze the factors that affect the trajectory category, so as to provides reference for formulating individualized intervention strategies.Methods:This study was a cross-sectional survey. From April 2020 to April 2021, young and middle-aged maintenance hemodialysis patients fromShangyu People′s Hospital were collected by convenience sampling method and conducted 4-time follow-up investigation. The survey tools included general information questionnaire, Demoralization Scale Mandarin Version (DS-MV) and Experiences in Close Relationship Scale-Short Form (ECR-S). Latent class growth model was used to identify trajectory patterns of demoralization, Logistic regression was used to identify predictors of demoralization trajectories.Results:Totally, 105 patients were enrolled in the present study. Three distinct trajectories were identified and named as "table high level group" 24 cases, "slow reduction group" 39 cases and "continuous reduction group" 42 cases. Univariate analysis showed that age, occupational status, average income per person in family, number of comorbidities, attachment anxiety scores were related to the category of demoralization trajectories ( F = 15.92, χ2 values were 9.16-15.95, all P<0.05). Multivariate Logistic regression analysis showed that age, occupational status, average income per person in family, number of comorbidities, and attachment anxiety scores were important predictors of patterns of demoralization trajectories in young and middle-aged maintenance hemodialysis patients. Conclusions:This study identified three distinct demoralization trajectories in young and middle-aged maintenance hemodialysis patients, clinical nursing should formulate individualized intervention strategies according to the types of patients′ delirium trajectories.