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.

Wastewater-based epidemiology(WBE)can effectively assess population health status,but it is lack of analytical methods which can simultaneously analyze a number of pharmaceuticals and biomarkers in wastewater.In this work,a method including sample pretreatment and instrumental detection for quantifying 83 kinds of pharmaceuticals and biomarkers in the influent of wastewater treatment plants(WWTPs)was established by sing solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS).The water sample(200 mL)with 83 kinds of target compounds was divided into two aliquots,which were then enriched and purified using HLB columns at pH=6.7 and pH=2 respectively,followed by elution with 6 mL of methanol and 6 mL of methanol containing 2%(V/V)formic acid,respectively,and then dried by nitrogen blown,concentrated,and finally redissolved to 0.5 mL,filtered through a nylon filter(0.22 μm).The target compounds in the samples were determined using UPLC-MS/MS in electrospray ionization under both positive and negative ion multiple reaction monitoring modes,with quantification using the internal standard method.The method exhibited good linearity(r>0.996)for the 83 kinds of target compounds in the concentration range of 0.1-500 ng/mL,and intra-day and inter-day precisions were 1.2%-16.5%.The recoveries of target substances in pure water and influent samples from a WWTP were 51.6%-166.6%and 56.4%-150.1%,respectively,with relative standard deviations of 0.2%-31.9%and 0.3%-20.9%,respectively.The method detection limits of target compounds were 0.02-7.72 ng/L.This method was applied to determine pharmaceuticals and biomarkers in the influent samples of a WWTP in Guangzhou,and 54 kinds of pharmaceuticals and 4 kinds of biomarkers were detected.The concentrations of acetaminophen and erythromycin were the highest among the pharmaceuticals,1.6-3.4 μg/L and 0.6-1.1 μg/L,respectively.The concentration of caffeine was the highest among the biomarkers,i.e.,33.3-43.9 μg/L.This method had high sensitivity,good stability and accuracy,and was suitable for detection of pharmaceuticals and biomarkers in the influent of WWTP,which could provide analytical method support for conducting studies on WBE.

OBJECTIVE: To observe the effects of the Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on hemorrhagic transformation and limb motor function after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in stroke patients. METHODS: A total of 130 stroke patients after rt-PA thrombolytic were divided into an acupuncture group (58 cases, 1 case dropped off) and a non-acupuncture group (72 cases, 7 cases dropped off) according to whether they received acupuncture treatment. Propensity score matching (PSM) was used to match each group, with 38 patients in each group. The patients in the non-acupuncture group received rt-PA thrombolytic therapy and western medical basic treatment. In addition to the basic treatment, the patients in the acupuncture group received Xingnao Kaiqiao acupuncture at Shuigou (GV 26), bilateral Neiguan (PC 6), and ipsilateral Sanyinjiao (SP 6), Chize (LU 5), once a day for 14 days. The incidence of hemorrhagic transformation within 30 days after onset was compared between the two groups. The Fugl-Meyer assessment (FMA) score and activities of daily living (ADL) score were observed at baseline and 30 days, 6 months, 1 year after onset in the two groups. The disability rate at 6 months and 1 year after onset was recorded, and safety was evaluated in both groups. RESULTS: The incidence of hemorrhagic transformation in the acupuncture group was 5.3% (2/38), which was lower than 21.1% (8/38) in the non-acupuncture group (P<0.05). At 30 days, 6 month, and 1 year after onset, the FMA and ADL scores of both groups were higher than those at baseline (P<0.01), and the scores in the acupuncture group were higher than those in the non-acupuncture group (P<0.01). The disability rate in the acupuncture group at 1 year after onset was 10.5% (4/38), which was lower than 28.9% (11/38) in the non-acupuncture group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSION The Xingnao Kaiqiao acupuncture method could reduce the incidence of hemorrhagic transformation in stroke patients after intravenous thrombolysis with rt-PA, improve their motor function and daily living ability, and reduce the long-term disability rate.
Humans ; Tissue Plasminogen Activator/adverse effects* ; Activities of Daily Living ; Prospective Studies ; Stroke ; Acupuncture Therapy ; Thrombolytic Therapy/adverse effects*

ObjectiveTo explore the effect of Chaishao Liujuntang on Hedgehog signaling pathway in rats with chronic atrophic gastritis （CAG） of liver depression and spleen deficiency. MethodWistar rats were randomized into normal group and modeling group. CAG with the liver depression and spleen deficiency syndrome was induced in rats in the modeling group with a compound method. After modeling， they were classified into the model group， vitacoenzyme group， Chaishao Liujuntang group， GDC-0449 （blocker） group， and Chaishao Liujuntang + GDC-0449 group. Normal group and model group were given （ig） normal saline. Vitacoenzyme and Chaishao Liujuntang group received （ig） corresponding drugs at 240 mg·kg^-1·d^-1 and 5.1 g·kg^-1·d^-1， respectively， and GDC-0449 group was treated （ip） with GDC-0449 at 50 mg·kg^-1·d^-1. For the Chaishao Liujuntang + GDC-0449 group， rats received GDC-0449 （ip） at 50 mg·kg^-1·d^-1 and Chaishao Liujuntang （ig） at 5.1 g·kg^-1·d^-1. The administration lasted 4 weeks. The pathological morphology of rat gastric mucosa was observed based on hematoxylin-eosin （HE） staining. mRNA and protein expression of sonic hedgehog （Shh）， 12th transmembrane receptor Patched1 （Ptch1）， and glioma-associated oncogene homolog 1 （Gli1） in gastric mucosa tissues was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot. Content of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with normal group， the model group demonstrated decrease in gland cells， glandular atrophy， large lumen volume， plasma cell infiltration， intestinal metaplasia， decrease in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa （P<0.01）， and rise of serum IL-1β and TNF-α content （P<0.01）. Compared with model group， vitacoenzyme group and Chaishao Liujuntang group showed ordered cells， alleviation of gland atrophy， and no obvious inflammatory infiltration， and GDC-0499 group and Chaishao Liujuntang + GDC-0449 showed no significant improvement. Significant rise in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa tissues of vitacoenzyme group and Chaishao Liujuntang group （P<0.01）， no significant difference in serum IL-1β content and significant decrease in TNF-α content in vitacoenzyme group （P<0.01）， significant reduction in content of serum IL-1β and TNF-α in Chaishao Liujuntang group （P<0.05， P<0.01） were observed compared with those in the model group. The mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa and the content of serum IL-1β and TNF-α were insignificantly different between the GDC-0449 group and Chaishao Liujuntang + GDC-0449 group. ConclusionChaishao Liujuntang can effectively improve the pathological state of gastric mucosa in CAG rats with liver depression and spleen deficiency， which may be related to the activation of Hedgehog signaling pathway and the decrease of IL-1β and TNF-α content.

Objective: To explore the effect of herb-partitioned moxibustion (HPM) on tight junctions (TJs) of intestinal epithelial cells in Crohn disease (CD) mediated by tumor necrosis factor-α (TNF-α)-nuclear factor kappa B (NF-κB)-myosin-light- chain kinase (MLCK) pathway. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an HPM group and a mesalazine (MESA) group, with 12 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was administered to establish CD models. When the model was confirmed a success, the HPM group rats were treated with HPM at Tianshu (ST 25) and Qihai (CV 6), while the MESA group rats were given MESA solution by lavage. When the intervention finished, the colonic epithelial tissues were separated, purified and cultured in each group to establish the intestinal epithelial barrier model in vitro, and TNF-α was added (100 ng/mL) in the culture medium and maintained for 24 h to establish an increased epithelial permeability model. Transepithelial electrical resistance (TEER) was used to examine the permeability of the barrier; Western blot was used to observe the expressions of the proteins related to TJs of intestinal epithelial cells mediated by TNF-α-NF-κB-MLCK pathway; immunofluorescence staining was used to observe the expressions and distributions of tight junction proteins in the intestinal epithelium. Results: After TNF-α induction, compared with the MC+TNF-α group, the TEER value increased significantly in the HPM+TNF-α and MESA+TNF-α groups (both P<0.001); the expressions of nuclear factor kappa B (NF-κB) p65, MLCK, myosin light chain (MLC), tumor necrosis factor receptor-associated factor 6 (TRAF6) and receptor interaction protein-1 (RIP1) decreased significantly (P<0.01 or P<0.05), and the expression of zinc finger protein A20 (A20) increased significantly (P<0.01); the expressions of occludin, claudin-1, zonula occludens protein 1 (ZO-1) and F-actin also increased significantly (all P<0.01). Compared with the MESA+TNF-α group, the expressions of MLC, occludin, claudin-1, ZO-1 and F-actin increased significantly in the HPM+TNF-α group (P<0.01 or P<0.05). Conclusion: HPM can protect or repair the damage of intestinal epithelial barrier in CD rats, which may be achieved through modulating the abnormal TJs in intestinal epithelium mediated by TNF-α-NF-κB-MLCK pathway.

Air Pollution ; Asthma/drug therapy* ; China ; Humans ; Treatment Adherence and Compliance

OBJECTIVE: To investigate the clinical characteristics of essential thrombocytopenia (ET) patients with positive mutations including JAK2, CALR, MPL, or negative mutations. METHODS: A total of 66 newly diagnosed ET cases from January 2016 to December 2018 in Department of Hematology, Huaian No.1 People's Hospital affiliated to Nanjing Medical University were analyzed. Statistical analysis data included the patient's sex, age, symptoms, thrombosis and embolism events, spleen omegaly, platelet count (Plt), leukocyte (WBC) count, hemoglobin (Hb), fibrinogen (FIB), thrombus elastic diagram (TEG), serum potassium, blood glucose (GLU), lactate dehydrogenase (LDH), JAK2, CALR and MPL mutations, treatment options, and efficacy. RESULTS: All the patients were not MPL-positive, and divided in three groups: JAK2 mutation (46 cases, 69.7%), CALR mutation (9 cases, 13.6%) and gene negative mutation (11 cases, 16.7%) group. The average age of patients in the JAK2 mutation group was 63.2 years old, and significantly higher than that in the CALR mutation group (51.8 year) and gene negative group (50.2 year) (P＜0.05). Compared with the JAK2 mutation group and gene negative group, the CALR mutation group had lower WBC count (6.3×10/L vs 13.79×10/L) (P=0.003) (6.3×10/L vs 9.70×10/L) (P=0.009). Also the Hb level of patients in CALR mutation group was lower than the JAK2 mutation group (121.22 g/L vs 136.2 g/L) (P=0.036). However, there was higher tumor burden in the CALR mutation group, compared with the gene negative mutation group (300.11 U/L vs 227.4 U/L) (P=0. 033). There was no significant difference among the three groups, such as the Plt counts, serum potassium level, GLU level and FIB level (P＞0.05). In addition, thrombus and embolism appeared in 30.3% (20/66) cases. 18.2% (12/66) cases were complicated with hyperkalemia, which significantly correlated with Plt counts (r=0.518). TEG was performed in 34 patients, of which 41.2% (14/34) had abnormal TEG and 55.9% (19/34) were accompanied by Plt count ＞ 1 000 ×10/L, but there was no significant correlation between them (r=0.134). After routine clinical treatment, all the 66 cases achieved partial or complete hematological remission, but the disease usually repeated. Until now 4.5% (3/66) cases had been converted to myelofibrosis (MF) all with JAK2 mutation, but without advancing to acute myeloid leukemia. CONCLUSION ET patients with JAK2 mutation have higher incidence, moreover were in older age. However, the patients with CALR mutations display lower WBC count and Hb level, but higher tumor burden. In short, the multiple gene mutations of ET showed different clinical features closely relates with the prognosis, thus providing guidance for the clinical diagnosis and treatment.
Aged ; Calreticulin ; genetics ; Humans ; Janus Kinase 2 ; genetics ; Middle Aged ; Mutation ; Primary Myelofibrosis ; Thrombocythemia, Essential ; Thrombocytopenia

Objective::To clarify the inhibitory effect of essential oil from Alpinia zerumbet rhizome (EOFAZ) on oxidized low-density lipoprotein (ox-LDL)-induced transformation of macrophage into foam cell and explore its possible mechanism. Method::THP-1 monocyte was incubated with 100 μg·L^-1 phorbol myristate acetate (PMA) to grow into macrophage, experiment was divided into 4 groups as follows, control group, model group (80 mg·L^-1 ox-LDL), EOFAZ at low dose (80 mg·L^-1 ox-LDL+ 4 μg·L^-1 EOFAZ)and EOFAZ at high dose (80 g·L^-1 ox-LDL+ 20 μg·L^-1 EOFAZ). Mathye thiazolye telrazliurn (MTT) method was employed to examine the influence of EOFAZ on macrophage viability. Western blot was used to analyze the expression level of cluster of differentiation 36(CD36) and ATP-binding cassette transporter A1(ABCA1) protein in macrophage. Enzyme-linked immunosorbent assay (ELISA) was used to detect cholesteryl ester contents in macrophage. Oil red O staining was applied to determine the accumulation of lipids in macrophage. Result::EOFAZ showed non-toxic effect on macrophage. Compared to control group, macrophage in model group displayed higher level of cholesteryl ester and lipid droplet(P<0.01), as well as significant increasing of CD36 expression (P<0.01), but no effect on ABCA1 expression. EOFAZ notably reduced the contents of lipids and cholesteryl ester(P<0.01), down-regulated expression of CD36 and up-regulated expression of ABCA1 in macrophage in comparison with the model group(P<0.01), indicating that EOFAZ inhibited transformation of macrophage into foam cell. Conclusion::EOFAZ could inhibit ox-LDL-induced transformation of macrophage into foam cell, the underlying mechanism may involves its ability to increase CD36 expression and decrease ABCA1 expression in macrophage.