Objective: To establish a method for determining the molecular weight and molecular weight distribution of Poly(Lactide-co-Glycolide Acid) (PLGA) using Size Exclusion Chromatography-Refractive Index-Multiangle Laser Light Scattering (SEC-RI-MALLS) and Size Exclusion Chromatography-Refractive Index (SEC-RID), and to compare the results obtained from these two methods.
Methods: For SEC-RI-MALLS, tetrahydrofuran was used as the mobile phase, Shodex GPC KF-803L was employed as the chromatographic column with a flow rate of 1 mL·min^-1, column temperature at 30 ℃, and an injection volume of 100 μL. For SEC-RID, tetrahydrofuran was also used as the mobile phase, Agilent PLgel 5 μm MIXD-D was used as the chromatographic column with a flow rate of 1 mL·min^-1, column temperature at 30 ℃, differential detector temperature at 35 ℃, and an injection volume of 20 μL. The molecular weight and molecular weight distribution were calculated using Agilent’s GPC software. The newly established methods were validated methodologically, and the molecular weight and molecular weight distribution of 13 batches of samples were determined.
Results: The precision, accuracy, stability, and repeatability tests for SEC-RI-MALLS showed RSD values of 1.35%, 1.58%, 1.53%, and 1.26%, respectively. The SEC-RID method exhibited good linearity (r=0.999 9), with RSD values for precision, accuracy, stability, and repeatability tests (n=6) of 2.05%, 1.62%, 1.30%, and 2.97%, respectively. The results obtained from SEC-RI-MALLS were lower than those from SEC-RID, and the molecular weight distribution coefficient was smaller, but the results from the paired T-test performed with the value measured by SEC-RID method and the value measured by SEC-RI-MALLS method multiplied a conversion coefficient of 1.5 showed no significant difference between the two methods.
Conclusion: Both methods are stable and reliable, and can be used for the determination of PLGA molecular weight and molecular weight distribution based on the specific situations.

Kounis syndrome is an acute coronary syndrome triggered by an allergic reaction, which is clinically rare and frequently subject to misdiagnosis or missed diagnosis. This article presents a case report of a 70-year-old male patient who developed a rash, pruritus, and chest pain following colon polyp resection. Coronary angiography revealed occlusion of the left anterior descending artery, and blood flow was restored after stent implantation. However, the patient experienced recurrent symptoms accompanied by loss of consciousness. Drug skin tests confirmed positive reactions to chlorhexidine and fondaparinux sodium, leading to a diagnosis of type Ⅱ Kounis syndrome. By avoiding allergenic drugs and combining antihistamines with symptomatic treatment to correct myocardial ischemia, the patient′s clinical symptoms significantly improved, and he eventually recovered and was discharged from the hospital. This case underscores the importance of maintaining vigilance for this syndrome in patients with allergies accompanied by chest pain and promptly identifying and avoiding allergens.

OBJECTIVE: To observe the effect of the direct stimulation of acupuncture at extraocular muscle attachment point on acquired extraocular muscle palsy. METHODS: Thirteen patients with acquired extraocular muscle palsy were treated with acupuncture directly at extraocular muscle (paralytic muscle) attachment point. Firstly, the intraocular conjunctival sac drops of topical anesthetic (procaine hydrochloride eye drops) were administered, 0.2 mL each time, once every 10 minutes, for a total of 3 times. Acupuncture was delivered immediately after the third drop. The sterile acupuncture needle for single use, 0.25 mm×25 mm, was inserted at the anatomical location of the corneal limbal attachment of paralytic extraocular muscle, with an angle of 10° to 15° formed between the needle tip and extraocular muscle, and a depth of 0.3 mm to 0.5 mm. Pivoted by the needle tip, the eyeball was moved passively towards the direction of normal action of orbital muscle, 30 to 50 times until the patient felt soreness of the eyeball; afterwards, the needle was removed. After acupuncture, levofloxacin eye drops were administered once (0.2 mL) at the affected eye. The treatment was given twice a week, and completed when diplopia disappeared. Before and after treatment, the diplopia and the synoptophore circumference were observed respectively. RESULTS: After 7 to 24 (15.46±5.56) times of direct stimulation with acupuncture at extraocular muscle attachment point, the symptoms of diplopia disappeared in 13 patients, the eye position restored to orthophoria, and the circumference of synoptophore was reduced to be (4.04±0.82)° from (19.38±3.98)° detected before treatment (P<0.05). CONCLUSION Acupuncture directly at extraocular muscle attachment can attenuate diplopia and improve ocular muscle function in patients with acquired extraocular muscle palsy.
Humans ; Acupuncture Therapy ; Male ; Female ; Middle Aged ; Adult ; Oculomotor Muscles/physiopathology* ; Aged ; Acupuncture Points ; Ophthalmoplegia/physiopathology*

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Blinding is an important means to control and reduce measurement bias in clinical research， and blinding assessment is the main method to measure the success of the blinding method. By summarizing the current situation of blinding assessment in randomized controlled trials （RCT） of acupuncture， it was found that the report rate of blinding assessment by acupuncture RCT was relatively low， and the studies reporting blinding assessment had several problems， such as incomplete assessment individuals， unreasonable assessment questionnaires， and unscientific analysis methods， and the setting of the assessment time point is controversial. Given the above problems， this paper discussed the key elements of blinding assessment individuals， assessment questionnaires， assessment time points， and analysis methods. It is suggested that blinding assessment should be carried out on all blinded participants and personnel in the study； the assessment questionnaire should be designed by direct inquiry， with responses designed using three or more categorical options that include an "unclear" option； the early stage of the trial should be taken as the mandatory time point for assessment， integrating the evaluation index of the James blinding index and the Bang blinding index， in order to standardize the application of blinding assessment in acupuncture RCT and improve the quality of acupuncture clinical research.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

ObjectiveTo detect the flexibility differences of Plasmodium berghei K173 （PbK173）-infected red blood cells with varying degrees of sensitivity to artemisinin-based drugs and to preliminarily explore the underlying mechanisms of the differences. MethodA total of 102 specific-pathogen-free （SPF） male C57BL/6 mice were randomly divided into three groups， with 30 mice each in the control group and PbK173-resistant （PbK173-R） group， and 42 mice in the PbK173-sensitive （PbK173-S） group. Except for the control group， the rest groups were vaccinated with 1×10⁷ PbK173-S/PbK173-R infected red blood cells to establish a mouse malaria model. During the administration and recovery periods （control group， PbK173-R/PbK173-S）， dihydroartemisinin （DHA， 40 mg·kg^-1） and malaridine （MD， 6 mg·kg^-1） were administered continuously for four days. Peripheral blood was taken from the PbK173-S/PbK173-R groups with an infection rate equal to or greater than 20%. Peripheral blood and each organ were taken on the first day at the end of administration （dosing period） and on the fifth day at the end of administration （recovery period）， and blood parameters and organ indices of each group were examined. The osmotic fragility of peripheral blood red blood cells in each group was detected using the red blood cell osmotic fragility test. Western blot was applied to determine the levels of Piezo1 and Band3 proteins in the red blood cell membrane. ResultDuring the administration and recovery periods， there were no significant differences between the PbK173-S MD group and the DHA group. During the administration period， there were no significant differences in hematological parameters between PbK173-S and PbK173-R in the MD group. However， during the recovery period， the red blood cell count， hemoglobin concentration and hematocrit of the PbK173-R group were significantly higher than those of the PbK173-S group （P<0.05） in the MD group. Compared with that of the control group， the osmotic fragility of the PbK173-S/PbK173-R groups was significantly enhanced （P<0.01）， and the osmotic fragility of the PbK173-S group was significantly stronger than that of the PbK173-R group （P<0.01）. The osmotic fragility of red blood cells in the PbK173-S group during the administration period was significantly stronger than that in the control group and PbK173-R group during the administration period （P<0.01）. The osmotic fragility of red blood cells in the PbK173-R group during the recovery period was significantly higher than that in the control group during the administration period and the PbK173-S group during the recovery period （P<0.05）. Compared with those in the control group， the Piezo1 protein and Band3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced （P<0.01）. Compared with those in the PbK173-R group， the Piezo1 protein and Band 3 protein in the red blood cell membrane of the PbK173-S group were significantly reduced. ConclusionThe flexibility of PbK173-infected red blood cells with different sensitivities to artemisinins differed. Plasmodium-infected red blood cells significantly reduced the levels of Piezo1 and Band3 proteins in the red blood cell membrane， and the erythrocyte flexibility exhibited a decreasing trend in the following order： normal group， PbK173-R group， and PbK173-S group.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objective To compare the clinical efficacies of unilateral biportal endoscopy(UBE)technique and percutaneous endoscopic lumbar discectomy(PELD)technique in the treatment of lumbar disc herniation.Methods The clinical data of 149 patients with lumbar disc herniation in our hospital were retrospectively analyzed and divided into the UBE group(n=80)and the PELD group(n=69)according to different surgical methods.The operation time,intraoperative fluoroscopy frequency,intraoperative blood loss,hospital stay,postoperative complications,visual analogue scale(VAS)score,Oswestry disability index(ODI)score,intervertebral disc height and vertebral canal area of the two groups were compared.Results The operation time in the UBE group was longer than that in the PELD group,and the intraoperative fluoroscopy frequency was fewer than that in the PELD group,the differences were statistically significant(P<0.001).There was no significant difference in the intraoperative blood loss or hospital stay between the two groups(P>0.05).There was no significant difference in the VAS or ODI scores at each time point between the two groups(P>0.05).There was no significant difference in the intervertebral disc height or vertebral canal area at each time point between the two groups(P>0.05).The postoperative vertebral canal areas of patients in the two groups were greater than those before surgery,and the differences were statistically significant(P<0.05).The incidence of postoperative complications in the UBE group was lower than that in the PELD group,the difference was statistically significant(P<0.05).Conclusion In terms of short-term efficacy,both PELD technique and UBE technique can effectively relieve the symptoms of low back and leg pain caused by lumbar disc herniation,and the UBE technique has longer operation time,but with fewer intraoperative fluoroscopy frequency,and lower incidence of postoperative complications.