Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

From an aqueous extract of the Angelica sinensis root head (guitou), nine pairs of lignanoid enantiomers [(+)-/(-)-1-(+)-/(-)-9], including three pairs of new structures [(+)-/(-)-1-(+)-/(-)-3] and two pairs of chiral separated enantiomers for the first time [(+)-/(-)-4 and (+)-/(-)-5], were isolated and chirally separated by column chromatography over different types of resin, normal and reversed phase silica gels, together with HPLC techniques using reversed phase and chiral columns. Their structures were determined by spectroscopic data analysis, theoretic calculation of electronic circular dichroism (ECD) spectra, and single-crystal X-ray diffraction. The chiral separated new enantiomers named (+)-/(-)-angelignanins Q-T [(+)-/(-)-1-(+)-/(-)-4] and (+)-/(-)-daphneresinol [(+)-/(-)-5], respectively.

Objective To explore the eradication rate of human papillomavirus(HPV)and gestational outcome of patients with high-grade squamous intraepithelial disease of the cervix(HSIL)after loop electrosurgical excision procedure(LEEP)by transvaginal dissection of the vesicorectal form the cervix.Methods A total of 53 patients treated with LEEP by transvaginal dissection of the vesicorectal form the cervix in Obstetrics and Gynecology Hospital,Fudan University from Jan to Dec,2019 were investigated.Clinical information of cervical cytological examination,HPV test and cervical biopsy under colposcopy were followed up for 6,12 and 24 months post-LEEP were collected.HPV infection in these 53 patients were compared before and after LEEP surgery.The rate of successful fertility of the cohort,the HPV conversion rate of patients with hysterectomy and LEEP done were compared.The association between the pathological type and positive surgical margin and the association between HPV infection type and positive surgical margin were analyzed.Results HPV infection rate of was 94.3%(50/53)and the proportion of HPV16 and/or 18 infection was 75.5%(40/53).Mono-HPV infection rate(69.8%,37/53)was significantly higher than mixed HPV infection rate(22.7%,13/53).Thirty-eight patients(71.7%)were found with positive surgical margin in previous LEEP operation.Fifteen patients had recurrence(28.3%)and 40 patients(75.5%)successfully delivered baby after surgery.Postoperative pathology was mainly HSIL,accounting for 66%(30/53),and 28.3%patients(15/53)had no pathological change.Forty cases had satisfying fertility-conservative operation outcome with negative surgical margin,and 38 patients eradicated HPV infection after LEEP,which took up 95%of patients with satisfying fertility-conservative operation.There was no significant difference of positive resection margin rate in between groups of HPV16/18 infection and other types.Five cases had successful delivery(12.5%,5/40)with 1 case of vaginal delivery and 4 cases of cesarean section.Among these 5 cases,3 cases undertook preventive cervical cerclage,with 1 case of vaginal delivery and 2 cases of cesarean sections.Conclusion HPV eradication rate and surgical outcome could be significantly improved by LEEP with transvaginal dissection of the vesicorectal from the cervix,which satisfied the fertility preservation of females at reproductive age.

Objective To investigate the clinical efficacy of arthroscopic measurement of intra-articular graft length in the application of total internal reconstruction of the anterior cruciate ligament(ACL).Methods The 60 patients with ACL injury treated between January 2020 and January 2022 were retrospectively analyzed.There were 37 males and 23 females,aged from 22 to 44 years.According to the different surgical methods,they were divided into two groups:conventional surgery group(conventional group)and pull-line measurement group(measurement group),with 30 cases in each group.In the conventional group,there were 20 males and 10 females,with an average age of(30.00±3.95)years old;the body mass index(BMI)was(22.58±1.41)kg·m-2;there were 9 cases on the left side and 21 cases on the right side;the time from injury to operation was(3.00±1.35)days.In the measurement group,there were 17 males and 13 females,with an average of(32.00±4.29)years;BMI was(23.29±1.39)kg·m-2;there were 12 cases on the left side and 18 cases on the right side;the time from injury to oper-ation was(3.00±1.27)days.The clinical data of the patients before surgery,6 months after surgery and 12 months after surgery were collected and recorded.The clinical efficacy of the two methods was compared in terms of postoperative VAS,KOOS,Lysholm score,IKDC score,knee stability(Lachman test,anterior drawer test and axial shift test),the degree of widening of bone tunnel diameter measured by CT at different stages of the postoperative period and MRI scoring system.Results At 12 months after surgery,the VAS of the measurement group was lower than that of the conventional group(P＜0.001).At 12 months after surgery,KOOS scores in the measurement group were higher than those in the conventional group,and there were statistical-ly significant differences in all scores except symptom scores(P＜0.05).Six months after operation,Lysholm total score and IKDC total score in the measurement group were higher than those in the conventional group,and the difference was statistically signifi-cant(P＜0.05).At 12 months after surgery,knee stability tests were performed,and the differences between the Lachman test,anterior drawer test and axial shift test measurement group and the conventional group were not statistically significant(P＞0.05).However,overall knee instability analysis showed that the knee stability of the measurement group was better than that of the con-trol group,and the difference between the groups was statistically significant(P=0.038).The imaging assessment of patients in both groups at 6 months after surgery showed that the widening of tendon tunnel diameter in both femur and tibia was reduced in the measurement group compared with the conventional group after surgery,and the difference was statistically significant(P＜0.05);MRI scores were higher in all patients in the measurement group those in the conventional group,at 6 months and 12 months agter surgery(P＜0.05).Conclusion Arthroscopic measurement of intra-articular cavity graft length in total internal technique for ACL reconstruction,high tendon utilization,good stability,the knee joint function has recovered satisfactorily within one year,and the therapeutic effect is affirmed.

Objective The objective of this study was to establish a mouse model of allergic rhinoconjunctivitis and investigate the role of the NLRP3 signaling pathway in allergic rhinoconjunctivitis.Methods Thirty-three female C57 mice(SPF)were randomLy divided into 3 groups:the control group,the experimental group,and the NLRP3-/-group.On days 0,4,7,14,and 21,the experimental group and NLRP3-/-group received a 0.2 mL intraperitoneal injection of medicine containing OVA(100 μg)and adjuvant Al(OH)3(4 mg),respectively.After an interval of 3 days,each eye and nose were dosed with 10 μL of 5%OVA for five consecutive days a week to induce allergic symptoms.During sensitization and excitation stages,the control group was replaced with an equiva-lent amount of PBS.Ocular and nasal symptoms were observed and scored.The levels of OVA-specific IgE,IL-4,IL-17,and IL-18 in serum were measured using ELISA,while changes in palpebral conjunctiva and nasal mucosa were assessed by hematoxylin-eosin staining.The expression of NLRP3 mRNA in conjunctival tissue and nasal mucosa was determined using real-time PCR analysis.Statistical analysis was performed using SPSS17.0 software with P<0.05 considered as statistically significant difference.Results The experimental group and NLRP3-/-group exhibited induced nasal and ocular allergic symptoms.In the experimental group,the duration of nasal allergy symptoms was(10.500±1.080)days,while the duration of eye allergy symptoms was(20.300±2.058)days.In the NLRP3-/-group,the duration of nasal allergy symptoms was(13.400±1.955)days,and for eye allergy symp-toms it was(20.900±2.132)days.The duration of nasal allergies in the NLRP3-/-group significantly exceeded that in the experimental group(P<0.05),whereas there were no significant differences observed in eye allergy durations between these two groups(P>0.05).Levels of OVA-specific IgE,IL-4,and IL-17 were significantly higher in both the experimental and NLRP3-/-groups compared to those in the control group(P<0.05).Additionally,serum IL-18 content increased significantly in the experimental group when compared with both control and NLRP3-/-groups(P<0.05).Conjunctival tissue lesions as well as nasal mucosa damage were evident in both experimental and NLRP3-/-groups.mRNA expression levels of NLRP3 within conjunctival tissue and nasal mucosa from the experimental group showed a significant increase when compared to those from both control and NLRP3-/-groups(P<0.05).Conclusion Allergic rhinoconjunctivitis pathogenesis is influenced by various factors;however,the involvement of NLPR3 signaling pathway promotes its development.

Objective:To investigate the distribution patterns of TCM syndrome elements and syndrome types in cancer-related fatigue (CRF).Methods:A cross-sectional survey was conducted on tumor patients attending the outpatient clinic and wards of the Department of Oncology, Xiyuan Hospital of China Academy of Chinese Medical Sciences from January to December 2021. Descriptive analysis was used to compare the distribution difference of TCM syndrome elements, symptoms and tongue symptoms of CRF and non-CRF patients. The TCM symptoms of CRF were clustered to summarize the common TCM syndromes of CRF.Results:A total of 306 tumor patients were finally included, of which 229 (75%) were CRF and 77 (25%) were non-CRF. Qi deficiency, blood deficiency, and cold-dampness were the most common deficiency and excess syndrome elements in CRF, and liver deficiency, yin deficiency, and blood stasis syndrome elements occurred more frequently in non-CRF than in CRF. TCM symptoms with a frequency greater than 50% in CRF patients, from high to low, were: fatigue > shortness of breath > insomnia or dreaminess > mental fatigue > forgetfulness>lazy speech > impatience, irritability, depression with sighing. The most frequent tongue symptoms, tongue coating, and pulse symptoms were respectively pale tongue, white and greasy coating or smooth white, and pulse deficiency. The symptoms with greater than 30% frequency in 77 non-CRF patients were, from highest to lowest: impatience and irritability or depression with sighing > insomnia or dreaminess > shortness of breath > dry mouth and throat > lumbar spine pain (excluding traumatic) > numbness of limbs > forgetfulness. The highest-ranked tongue, tongue coating, and pulse symptoms were pale tongue, red tongue or less coating, no coating, and thin pulse, respectively. Through clustering analysis, six common syndromes of CRF were obtained, including qi and blood deficiency syndrome, heart and liver blood deficiency syndrome, kidney yang deficiency syndrome, qi and yin deficiency syndrome, spleen deficiency and qi stagnation syndrome, and cold dampness and spleen stagnation syndrome.Conclusions:CRF is a common symptom of different types of tumors. Generally, deficiency syndrome is the main symptom. Qi deficiency and blood deficiency are the common syndrome elements. Common symptoms of high frequency and tongue and pulse are fatigue, shortness of breath, mental fatigue, forgetfulness, pale tongue and thin pulse. The common TCM syndrome types can be preliminarily summarized into 6 types: qi and blood deficiency syndrome, heart and liver blood deficiency syndrome, kidney yang deficiency syndrome, qi and yin deficiency syndrome, spleen deficiency and qi stagnation syndrome, cold dampness and spleen stagnation syndrome.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Objective:To investigate the influences of Neferine(Nef)on inflammatory injury in nephrotic syndrome(NS)rats by regulating the MAPK/NF-κB pathway.Methods:SD rats were separated into control check group(CK group),Model group,low-dose Nef group(Nef-L group,2.5 mg/kg),high-dose Nef group(Nef-H group,5 mg/kg),prednisone acetate group(PA group,6.3 mg/kg),Anisomycin(MAPK agonist)group(5 μmol/L),Nef-H+Anisomycin group(5 mg/kg+5 μmol/L),with 12 rats in each group.Except for the CK group,all other groups were injected with doxorubicin through the tail vein to induce the NS rat model.Rats in CK group were injected with an equal volume of normal saline through the tail vein at the same time.After successful modeling,dosing treatment was performed once a day for 4 weeks.Detected 24-hour urine protein content,serum creatinine(Scr),albumin(ALB),urea nitro-gen(BUN)levels,renal tissue pathology,and levels of TNF-α,IL-6,and IL-1β in renal tissue;TUNEL staining was performed to detect cell apoptosis in rat kidney tissue;Western blot was performed to detect the expression of p-p38,p-JNK,p-ERK1/2 and p-NF-κB p65 proteins in rat kidney tissue.Results:Compared with CK group,Model group had severe renal tissue pathological damage,the 24 h urinary protein,Scr,BUN,TNF-α,IL-6,IL-1β,apoptosis rate,p-p38,p-JNK,p-ERK1/2,p-NF-κB p65 protein expressions were increased,while ALB level was decreased(P<0.05);compared with Model group,the renal tissue pathological damage of rats in Nef-L group,Nef-H group and PA group were severe,the 24 h urinary protein,Scr,BUN,TNF-α,IL-6,IL-1β,apoptosis rate,p-p38,p-JNK,p-ERK1/2,p-NF-κB P65 protein expressions were decreased,while ALB level was increased,the renal tissue pathological damage in the Anisomycin group was aggravated,the 24 h urinary protein,Scr,BUN,TNF-α,IL-6,IL-1β,apoptosis rate,p-p38,p-JNK,p-ERK1/2,p-NF-κB p65 protein expressions were increased,while ALB level was decreased(P<0.05);Anisomycin attenu-ated the effects of high doses of Nef on NS rats.Conclusion:Nef may alleviate the inflammatory injury in NS rats by inhibiting MAPK/NF-κB signaling pathway.

ObjectiveTo evaluate the lipid-lowering activity of Quansanqi tablets（QSQ）， an innovative new drug of Panax notoginseng. MethodMice and golden hamsters were used to establish a hyperlipidemia model by injecting egg yolk milk and feeding high-fat diets. The levels of total cholesterol （TC），triglyceride （TG），low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were detected， and liver function indicators ［alanine aminotransferase （ALT）， aspartate amino-transferase （AST）， and alkaline phosphatase （ALP）］ of golden hamsters were detected. Hematoxylin-eosin （HE） staining was used to observe the degree of liver injury. In the experiments， a normal group， a model group， an atorvastatin calcium group， and low-， medium-， and high-dose QSQ groups （0.32， 0.64， 1.28 g·kg^-1 for mice， and 0.16， 0.32， 0.64 g·kg^-1 for golden hamsters） were set up. ResultCompared with the normal group， the acute hyperlipidemia model mice showed increased TC， TG， and LDL-C levels （P<0.01）， and the hyperlipidemia model mice showed increased TC and LDL-C levels （P<0.01）. Additionally， the hyperlipidemia model golden hamsters showed increased serum TC， TG， LDL-C， ALT， AST， and ALP levels （P<0.05， P<0.01）. HE staining indicated the presence of fat accumulation in the liver， accompanied by inflammatory reactions. Compared with the model group， QSQ of various doses could reduce TC， TG， and LDL-C levels in acute hyperlipidemia model mice （P<0.05， P<0.01）， and the high-dose QSQ could reduce TC and LDL-C levels （P<0.01） and increase HDL-C level （P<0.05） in hyperlipidemia model mice， as well as reduce TC， TG， and LDL-C levels in hyperlipidemia model golden hamsters （P<0.05， P<0.01）， especially in the first two weeks. In addition， atorvastatin calcium could further increase ALT， AST， and ALP levels （P<0.05， P<0.01） and aggravate liver function damage， while low-dose QSQ could reduce ALT， AST， and ALP （P<0.05）， and medium- and high-dose QSQ did not cause further liver function damage. ConclusionQSQ have a significant lipid-lowering effect on different hyperlipidemia model animals and can improve liver function and liver injury.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic