In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

Objective:To investigate the efficacy and safety of transcatheter arterial embolization(TAE)in the treatment of refractory bleeding caused by head,neck,and maxillofacial trauma.Methods:The clinical data of 26 patients with refractory bleeding caused by head,neck and maxillofacial trauma who were treated with TAE in The First Affiliated Hospital of Zhengzhou University and The Third People's Hospital of Henan Province were analyzed retrospectively,including 16 males and 10 females,with an average age of 57.96±15.52 years.All patients were treated with TAE because of the poor effect of medication,packing,and other measures and repeated bleeding.The clinical data,operation success rate,effective hemostasis rate,30-day clinical success rate,and postoperative complica-tions were analyzed.The patients were followed up for 3 to 6 months.Results:The operation success rate of TAE was 100%.The bleed-ing symptoms of all patients were effectively controlled,and the effective hemostasis rate was 100%.The hemoglobin level was in-creased from(96.21±12.42)g/L before operation to(111.38±7.70)g/L at 3 days after operation(P<0.001).After operation,3 pa-tients had slight swelling,pain,or skin color changes in the head,neck,and maxillofacial region,which were effectively relieved or dis-appeared after symptomatic treatment;2 patients died of severe traumatic brain injury and cerebral edema.No serious complications such as cerebral infarction occurred in any patients.There was no rebleeding in any patients within 3 to 6 months of post-discharge follow-up.Conclusion:TAE has definite curative effect and good safety for refractory bleeding caused by head,neck,and maxillofa-cial trauma,and has high clinical application value.

Objective:To compare the difference between the operation of ureteral calculi patients with COVID-19 infection during COVID-19 infection and after recovery to find out the best timing for surgery.Methods:The clinical data of 327 ureteral calculi patients with COVID-19 infection were retrospectively analyzed, including 141 cases who underwent ureteroscopic surgery. According to the time of ureteroscopic surgery, the patients were divided into two groups: operation before recovery of COVID-19 infection group ( n=81) and operation after recovery of COVID-19 infection group ( n=60). The success rate of primary surgery, stone removal incidence, complication inciednce, mortality, operation time, postoperative hemoglobin decline, hospital stay, and total hospitalization cost and other indicators of the two groups were compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), independent t-test was used for inter-group comparison. Chi-test or continuous correction Chi-test was used for inter-group comparison for count data. Results:The success rate of primary surgery (38.3%, 31/81), stone removal rate (86.4%, 70/81) in the operation before recovery of COVID-19 infection group were significantly lower than those in the operation after recovery of COVID-19 infection group [80.0% (48/60), 98.3% (59/60)], and the differences were statistically significant ( P< 0.05). The incidence of complication, postoperative hemoglobin decline [(2.1±0.6) g/L vs (0.6±0.3) g/L], hospital stay [(14.7±3.6) d vs (4.1±1.1) d], total hospitalization cost [(34 733.3±4 412.4) yuan vs (21 919.7±3 251.3) yuan] of the operation before recovery of COVID-19 infection group were significantly higher than those in the operation after recovery of COVID-19 infection group, and the differences were statistically significant ( P< 0.001). The operation time of the operation before recovery of COVID-19 infection group was shorter [(16.9±5.4) min vs (37.7±8.9) min], and the difference was statistically significant ( P< 0.001). There was no significant difference in mortality between the two groups (3.7% vs 0, P> 0.05). Conclusion:The risk of surgical treatment for ureteral calculi patients with COVID-19 infection is high, The treatment of them should mainly be conservative treatment, and operation should be performed after COVID-19 infection is cured.

Objective To analyze the pathogenic characteristics and drug sensitivity of candidaemia,and construct a short-term mortality risk prediction scoring model.Methods The clinical data of patients with candidaemia admitted to the 909 Hospital of Joint Logistics Support Force from January 2011 to December 2020 were retrospectively analyzed,and the composition of pathogen composition,drug sensitivity test results and incidence of hospitalized patients were analyzed.324 cases of candidaemia were randomly divided into modeling group(190 cases)and validation group(134 cases),and the risk factors were screened by binary logistic regression.According to the odds ratio(OR)score,the 30 day mortality risk prediction scoring model was constructed,and the predictive performance of the model was verified both in modeling and validation groups.Results 356 strains of Candida including 126 strains of C.albicans(35.39%),79 strains of C.tropicalis(22.19%),74 strains of C.parapsilosis(20.79%),48 strains of C.glabrata(13.48%),14 strains of C.guilliermondii(3.93%),8 strains of C.krusei(2.25%),and 7 strains of other Candida(1.97%)were detected in 336 patients with candidemia.The incidence of candidaemia among hospitalized patients increased from 0.20 ‰ in 2011 to 0.48 ‰ in 2020.The resistance rate of candida to amphotericin B was significantly lower than that of fluconazole,voriconazole and itraconazole(P＜0.05).Among the 324 cases included in the model,95 patients died in 30 days after diagnosis,and the mortality rate was 29.32%.The proportion of males,fever,and parenteral nutrition in modeling group was significantly higher than that in validation group(P＜0.05),while the proportion of chronic lung disease and surgical history within one month were lower than those in validation group(P＜0.05).Logistic regression analysis showed that chronic renal failure,mechanical ventilation,severe neutropenia,failure to receive anti-fungal treatment within 72 hours,and APACHE Ⅱ≥20 were risk factors for short-term death of candidaemia,the OR values were 3.179,1.970,2.979,2.080,and 2.399,and the risk scores were 6,4,6,4,and 5,respectively.The area under the curve(AUC)of the risk scoring model for modeling group was 0.792(95%CI 0.721-0.862),and the result of Hosmer-Lemeshow(H-L)test was P=0.305;The AUC of validation group was 0.796(95%CI 0.735-0.898),and the H-L test result was P=0.329.A risk score≤8 indicated a low risk group for short-term mortality,a score of 9-15 indicated a medium risk group,and a score≥16 indicated a high risk group.Conclusions The incidence of candidemia in hospitalized patients is increasing and the mortality is high.The risk prediction score model can effectively predict the short-term prognosis and facilitate the early identification of the prognosis.

Prostatitis is one of the three most common prostate diseases in men,the other two being prostatic hyperplasia and prostate cancer,and about 50% of men worldwide have been attacked by prostatitis during their lives.The incidence of infertility is significantly higher in patients with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)than in those without it,which is mainly attributed to the changed semen composition of the CP/CPPS patients.Using the key words chronic prostatitis,chronic pelvic pain syndrome,sperm,semen,and seminal plasma,we searched PubMed and Medical Lines online for originals,review articles,clin-ical trials,case reports and associated citations on humans and animals published up to 2024.We comprehensively reviewed the previ-ous studies and investigations relating chronic prostatitis,seminal plasma change and sperm quality,and discussed the impact of the change of semen composition on sperm quality.

Objective:To observe any effect of combining repetitive peripheral magnetic stimulation (rPMS) with repeated transcranial magnetic stimulation (rTMS) on upper limb dysfunction after a stroke.Methods:A total of 128 stroke survivors were randomly divided into a control group, a central group, a peripheral group and a combined group, each of 32. In addition to conventional medical treatment and rehabilitation training, the combined group were given 1Hz rTMS over the M1 area of the unaffected hemisphere and rPMS on the Erb point of the affected upper limb. The central group were given rTMS with sham rPMS, the peripheral group was given rPMS and sham rTMS, while the control group received sham rTMS and sham rPMS. Both the rPMS and rTMS, genuine and sham, were administered once daily for 15 minutes each time, 6 days a week for 4 consecutive weeks. Before and after the treatment, the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT) were administered to evaluate the upper limb motor function of the subjects′ affected side. The Modified Barthel index (MBI) quantified their ability in the activities of daily life.Results:After the intervention, the average FMA-UE, WMFT and MBI scores had improved significantly in all four groups. After the intervention the average FMA-UE, WMFT and MBI scores of the combined, central and peripheral groups were all significantly better than the control group′s averages, with those of the combined group significantly superior to the central and peripheral groups.Conclusion:Both rTMS and rPMS can promote the recovery of upper limb motor function after a stroke and ability in daily life activities. Their combination can achieve better effects.

Objective:To observe the effect of early weightbearing after anterior cruciate ligament reconstruction (ACLR) on lower limb motor function, activation of the knee muscles and the stability of the knee joint.Methods:Forty-four persons who had received ACLR were divided at random into a control group and an experiment group, each of 22. In addition to conventional rehabilitation treatment after surgery, the control group underwent weightbearing training from the 8th day after the surgery, while the experimental group began weight-bearing training from the 3rd postoperative day. Both groups had their motor functioning evaluated using the International Knee Scoring Committee (IKDC) knee subjective evaluation form 3 days after the operation, and then 6 and 12 weeks later. Their pain perceptions were quantified on the same schedule using visual analogue scoring (VAS), and protractor measurements documented active range of motion (AROM). Electromyography (AEMG) of the medial head and rectus femoris muscle was also performed, and the stability of the knee joint was assessed using the KT-1000 test.Results:After the intervention, the average IKDC score, VAS score, knee extension and flexion AROMs, medial quadriceps head AEMG ratio, and rectus femoris muscle AEMG ratio improved to different degrees in the two groups. At 6 weeks the average pain score, knee extension and flexion ranges of motion, quadriceps medial head AEMG ratio, and rectus femoris AEMG ratio of the experimental group were all better than the control group′s averages. At 12 weeks the average IKDC subjective knee function score in the experimental group was also superior.Conclusions:Supplementing conventional rehabilitation with early weight-bearing can significantly improve the recovery from anterior cruciate ligament reconstruction. Beginning on day 3 after the operation gives the best results.

Objective To explore the clinical value of anti-Müllerian hormone(AMH)to optimize endocrine therapy for peri-menopausal early breast cancer.Methods Two hundred and four patients of pre-menopausal breast cancer aged 45-55 years old between 2020 and 2023 were enrolled,and AMH≤0.1 ng/mL was considered as cut-off value for menopause.Switching from selective estrogen receptor modulator(SERM)to aromatase inhibitor aromatase inhibitor(AI)and initial endocrine therapy regimens were based on AMH,follicle-stimulating hormone(FSH)and estradiol(E2).Results Pre-chemotherapy AMH level was significantly negatively correlated with FSH level(P<0.001).Among 100 cases who were amenorrhea for one year during SERM treatment,42 cases did not have AMH testing.Fourteen out of the 42 cases switched to AI within one year,and ovarian function recovery(OFR)occurred in 2 cases after AI switching.Fifteen cases with AMH>0.1 ng/mL did not switch to AI within one year.Forty among 43 cases with AMH≤0.1 ng/mL switched to AI,after a significantly shorter median SERM treatment duration(3.15 months vs.8.14 months,P<0.001)and a significantly lower OFR rate(0 vs.12.5%,P=0.023)compared with those who did not test AMH but switched to AI.AMH≤0.1 ng/mL was an independent risk factor of transition to menopause shortly in peri-menopausal patients(OR=35.857,P<0.001).Among 104 cases with AMH tested before adjuvant chemotherapy,69 cases had AMH>0.1 ng/mL.Thirty-one out of the 69 cases were treated with ovarian function suppression(OFS)initially and 38 with SERM initially.Thirty-five cases with AMH≤0.1 ng/mL were all treated with SERM initially,with a higher rate of switching to AI(71.4%vs.23.7%,P<0.001)and a shorter SERM treatment duration(6.52 months vs.13.56 months,P=0.016)compared with the 38 cases(AMH>0.1 ng/mL)treated initially with SERM.After a median 30-month follow-up,no recurrence was observed in these thirty-five cases treated with SERM initially and AMH≤0.1 ng/mL,just like in OFS group.And they had a tendency of improved survival outcome compared with those treated with SERM initially and AMH>0.1 ng/mL(Log Rank P=0.076).Conclusion AMH could evaluate and predict menopause accurately,resulting in optimizing endocrine therapy for peri-menopausal patients effectively and safely.