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.

Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Objective To investigate the new-onset conduction block after transcatheter aortic valve replacement (TAVR) and summarize the relevant experience. Methods The perioperative data of TAVR patients in the Second Hospital of Hebei Medical University from January 2016 to February 2023 were collected, and the new-onset incidence of conduction block after TAVR was analyzed retrospectively. Results Finally 352 patients were included, including 225 males and 127 females, with an average age of (67.2±5.1) years, among whom 256 patients were treated with Venus-A valves, 69 patients with Vita-Flow valves, and 27 patients with J-Valve valves. There were 38 (10.8%) patients of new-onset postoperative block. There were 6 (1.7%) patients of new-onset postoperative grade Ⅲ atrioventricular block, including 5 (2.0%) patients of Venus-A and 1 (1.4%) patient of Vita-Flow. Conduction function was restored in 2 patients within 14 days after surgery, and failed to be restored in 4 patients, who then received permanent pacemaker implantation in the Department of Cardiology. There were 27 (7.7%) patients of new left bundle branch block after surgery, including 22 (8.6%) patients of Venus-A, 4 (5.8%) patients of Vita-Flow and 1 (3.7%) patient of J-Valve; and conduction function was restored within 7 days after surgery in 23 patients, and 5 (1.4%) patients developed new right bundle branch blocks after surgery including 4 (1.5%) patients of Venus-A and 1 (1.4%) patient of Vita-Flow. Conclusion New-onset conduction block is a common complication after TAVR, and the new-onset rate of left bundle branch block is the highest, followed by the grade Ⅲ atrioventricular block. Mastering reasonable methods and applying appropriate strategies can effectively reduce the new-onset rate of postoperative conduction block and improve the overall success rate of TAVR surgery.

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*

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 establish a closed-loop management system for the whole-process traceability of outpatient drugs based on internet of things （IoT） and blockchain technology， and evaluate its implementation effects. METHODS A closed-loop management system for the whole-process traceability of outpatient drugs covering the entire drug lifecycle was designed using drug traceability codes integrated with IoT and blockchain technology. System effectiveness was evaluated from three dimensions： work efficiency， medication management quality and data safety by comparing indicators such as the acceptance time of incoming drugs and the number of collected drug traceability codes before the system implementation （October to December 2024） and after the system implementation （January to March 2025）. RESULTS A closed-loop management system for the whole-process traceability of outpatient drugs， centered around the drug traceability code management system， was successfully established. The acceptance time for incoming drugs was shortened from （4.65±0.26） h before implementation to （0.34±0.08） h after implementation （P＜ 0.05）. The number of collected drug traceability codes increased from 419 018 to 1 236 522， and the coverage rate of traceability codes rose from 28.36% to 89.88% （P＜0.05）. The time pharmacists spent on drug expiry management per week decreased from （128.40±19.20） min to （0.56±0.13） min （P＜0.05）， and the dispensing time for a single prescription （excluding a part of injections and repackaged drugs） was reduced from （143.25±17.67） s to （15.24±10.08） s （P＜0.05）. The time for drug return was reduced from 129.90 （122.32， 137.00） s to 104.36 （89.91， 117.33） s（P＜0.05）； the number of drug dispensing errors decreased from 2 cases to 0 cases. After the system was launched， there were no data security incidents in our outpatient pharmacy. CONCLUSIONS The constructed closed-loop management system for the whole-process traceability of outpatient drugs can significantly enhance drug traceability accuracy and drug management quality， improve pharmacist work efficiency， and reduce drug management risks， thus providing a feasible solution for the digital transformation of hospital pharmaceutical services.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Nicotinamide adenine dinucleotide (NAD⁺) is a central and pleiotropic metabolite involved in multiple cellular energy metabolism, such as cell signaling, DNA repair, protein modifications, and so on. Evidence suggests that NAD⁺ levels decline with age, obesity, and hypertension, which are all significant CVD risk factors. In addition, the therapeutic elevation of NAD⁺ levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances antioxidation and metabolism in vascular cells of humans with vascular disorders. In preclinical animal models, NAD⁺ boosting also extends the health span, prevents metabolic syndrome, and decreases blood pressure. Moreover, NAD⁺ storage by genetic, pharmacological, or natural dietary NAD⁺-increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models and humans. Here, we discuss NAD⁺-related mechanisms pivotal for vascular health and summarize recent research on NAD⁺ and its association with vascular health and disease, including hypertension, atherosclerosis, and coronary artery disease. This review also assesses various NAD⁺ precursors for their clinical efficacy and the efficiency of NAD⁺ elevation in the prevention or treatment of major CVDs, potentially guiding new therapeutic strategies.
Humans ; Cardiovascular Diseases/physiopathology* ; NAD/metabolism* ; Animals ; Hypertension/metabolism*

This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

OBJECTIVE: To systematically evaluated clinical efficacy of Kirschner's needle and elastic intramedullary nail fixation in treating proximal humeral fractures in children by Meta-analysis. METHODS: Literature on the treatment of proximal humeral fractures in children with Kirschler needles and elastic intramedullary nails published on Wanfang, VIP, CNKI and China biology medicine (CBM), PubMed, Embase, and Web of Science databases were searched from the establishment of databases to October, 2023. Literature extraction, management and data entry were performed by Endnote X9 and Excel 2019, and Meta-analysis was conducted by RevMan 5.3 software. The operation time, hospital stay, fracture healing time, shoulder joint extension range of motion, disabilities of arm, shoulder and hand(DASH) questionnaire score, Neer score or Constant-Murley score and complications were compared between two groups. RESULTS: A total of 7 literatures were included, 1 was prospective study, 6 were retrospective cohort study. There were 521 children, 264 children in Kirschner wire group and 257 children in elastic intramedullary nail fixation group. The results of Meta analysis showed operation time[WMD=-12.61, 95%CI(-24.89, -0.33), P=0.04], fracture healing time[WMD=-0.26, 95%CI(-0.49, -0.02), P=0.03], total complication rate [OR=6.83, 95%CI(3.33, 14.01), P<0.001], nail tract infection rate[OR=6.77, 95%CI(1.72, 26.69), P=0.006] and displacement fracture rate[OR=3.57, 95%CI(1.35, 9.44), P=0.01] between two groups had statistically differences(P>0.05), while there were no statistically significant difference in comparison of hospital stay, shoulder joint extension range of motion, DASH, Neer score, Constant-Murley score, and incidence of skin irritation between two groups (P>0.05). CONCLUSION Kirschner's needle internal fixation has a short operation time and simple operation, but it has a higher incidence of complications compared with elastic nail internal fixation technique. In terms of efficacy and safety, elastic intramedullary nail fixation is one of the options for the treatment of proximal humeral fractures in children.
Humans ; Fracture Fixation, Intramedullary/instrumentation* ; Child ; Shoulder Fractures/physiopathology* ; Bone Nails ; Bone Wires ; Male ; Needles ; Female

OBJECTIVE: To compare the effects of different concentrations of ropivacaine femoral nerve block on postoperative pain and early exercise fllowing total knee arthroplasty(TKA). METHODS: A total of 90 patients who underwent primary TKA between September 2022 and February 2023 were consecutively enrolled in this study. The cohort consisted of 34 males and 56 females, with a mean age of (66.66±7.03) years old. According to different concentrations of ropivacaine, patients were divided into 0.1% group, 0.2% group and 0.4% group, with 30 patients in each group. The age, gender, body mass index(BMI), American Society of Aneshesiologists(ASA) grade, operation time, anesthesia time, tourniquet using time, Post Anesthesia care unit(PACU) stay duration, ambulation time, first reaching to Bromage 0 grade time, visual analogue scale(VAS), hospitalization period and postoperative adverse reactions were compared among the three groups. RESULTS: All 90 patients were followed up for an average of (31.56±5.62) days, and no postoperative adverse reactions occurred. There were no significant differences among the three groups in terms of age, gender, BMI, ASA classification, operation time, anesthesia time, tourniquet application time, PACU stay duration, and hospitalization period (P>0.05). Significant differences were observed in VAS scores at 1, 2, 4, 6, and 12 hours post-operation among the three groups (P<0.05). Additionally, significant variations were noted in ambulation time and the first reaching to Bromage level 0 time among the three groups (P<0.05). In terms of postoperative pain, the VAS of the 0.1% group at 1, 2, 4, 6, and 12 hours after surgery(1.93±0.52), (2.57±0.77), (3.10±0.71), (3.10±0.71), (3.07±0.45) points were higher than those of the 0.4% group (1.57±0.50), (2.10±0.55), (2.23±0.57), (2.47±0.73), (2.50±0.57) points, and the differences were statistically significant (P<0.05);the VAS of the 0.1% group at 4, 6, and 12 hours after surgery were higher than those of the 0.2% group (2.43±0.57), (2.53±0.57), (2.63±0.56) points, and the differences were statistically significant (P<0.05);there was no statistically significant difference in VAS between the 0.2% group and the 0.4% group (P>0.05). In terms of early postoperative mobility, the time to ambulation time (8.30±2.76) h and the time to achieve the first Bromage grade 0 (6.13±2.18) h were significantly prolonged in the 0.4% group compared to both the 0.1% group (6.93±1.76) h, (4.17±1.18) h and the 0.2% group (6.53±1.59) h, (4.87±1.53) h. No statistically significant differences were observed between the 0.1% and 0.2% groups (P>0.05). CONCLUSION 0.2% ropivacaine femoral nerve block can effectively reduce postoperative pain after TKA and can perform early exercise earlier.
Humans ; Male ; Female ; Ropivacaine/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Aged ; Nerve Block/methods* ; Femoral Nerve/drug effects* ; Middle Aged ; Pain, Postoperative/drug therapy* ; Anesthetics, Local/administration & dosage* ; Amides