AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease(KBD)in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion(ROM)with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients.Methods To investigate the registered KBD patients from KBD areas in Shaanxi Province,we measured the general demographic data of the patients were collected and the ROM of the knee joint(flexion and extension),the ankle joint(dorsiflexion and plantar flexion),and the muscle atrophy related indexes such as the upper arm circumference,thigh circumference,calf circumference and grip strength.According to the population characteristics,i.e.,gender,age,body mass index(BMI)and KBD grade,the median and quartile of joint ROM and muscle atrophy of KBD patients were reported,and then the differences in each index among different groups were analyzed.Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender,age and BMI.Results A total of 480 patients with KBD were investigated in this study,who consisted of 249(51.9％)males and 231(48.1％)females,with an average age of(63.10±7.32)years and an average BMI of(23.49±8.90)kg/m2.The knee flexion ROM,knee extension ROM,ankle dorsiflexion ROM and ankle plantar flexion ROM were[105.0(95.0,120.0)]°,[0.0(-15.0,0.0)]°,[5.0(0.0,15.0)]° and[20.0(15.0,30.0)]°,respectively,in KBD patients in Shaanxi Province.The left thigh circumference,right thigh circumference,left calf circumference,right calf circumference,and upper arm circumference were[43.0(40.0,47.0)]cm,[43.0(39.0,47.0)]cm,[29.0(27.0,32.0)]cm,[29.5(27.0,32.0)]cm,[27.0(25.0,30.0)]cm,respectively.The left hand grip strength and right hand grip strength were[13.4(9.5,18.4)]kg and[13.9(9.8,18.2)]kg,respectively.With the increase of age,the extension range of the left and right knee joints of KBD patients showed a decreasing trend(H=31.499,31.847;all P＜0.001).The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group,with statistically significant differences(H=7.753,12.333;P=0.021,0.002).The knee flexion,thigh circumference,and calf circumference of the left and right sides showed a decreasing trend under different KBD grades(H=14.345,17.256,8.000,8.462,8.558,9.633;all P＜0.05).Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference,calf circumference,and grip strength in patients with KBD(all P＜0.05).There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD(P＜0.01).Conclusion The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province,and there is a correlation between joint motion and muscle atrophy.

Objective To perform laboratory detection and molecular traceability analysis on a case of imported kala-azar in Shenzhen to determine the infection strain. Methods Bone marrow puncture fluid and blood samples from a case of kala-azar in Shenzhen were collected for laboratory tests. The patient's bone marrow puncture fluid smears were stained with Giemsa and examined under a microscope. Blood samples were examined for antibodies using the rk39 visceral leishmania rapid diagnostic reagent. Whole blood DNA was extracted, and the ITS-1 sequence was amplified by PCR, sequenced and aligned, and a phylogenetic tree was constructed based on the ITS-1 sequence. Results Microscopic examination of the patient's bone marrow smears revealed a large number of Leishmania amastigotes without flagella, confirming the diagnosis of kala-azar. The patient's blood was tested positive with the rk39 rapid diagnostic reagent, and PCR amplification yielded an ITS-1 gene product sequence that matched the expected size. Sequence alignment with the NCBI database showed 100% sequence similarity with the ITS-1 gene sequence of Leishmania infantum, confirming the infecting strain as Leishmania infantum. Phylogenetic tree construction of the amplified ITS-1 sequence revealed clustering into a clade with Leishmania infantum , and close to KC347299, one of the reference sequence selected. Conclusions The case of kala-azar in Shenzhen was caused by Leishmania infantum. Kala-azar still occurs in China, so the diagnostic technology of medical personnel in non-epidemic areas should be strengthened so that they can actively use new diagnostic technologies to assist in diagnosis, thus improving their prevention and control ability of Leishmania parasites.

Objective:To explore the current status of barriers to participation in phaseⅡcoronary artery bypass grafting (CABG) patients and the factors influencing them, and to provide new ideas for reducing barriers to participation in rehabilitation and improving the participation rate in cardiac rehabilitation.Methods:For this study, a cross-sectional survey research method was utilized. The study included 334 patients who underwent CABG and were admitted to the Second Hospital of Hebei Medical University between June 2022 and May 2023. These patients were selected using the convenience sampling method. A General Information Questionnaire, the Cardiac Rehabilitation Barriers Scale (CRBS-C/M), and a Questionnaire on the Knowledge of Information Related to Cardiac Rehabilitation were used to conduct the survey. Multiple linear regression was used to analyze the independent influencing factors on barriers to participation in phase Ⅱ cardiac rehabilitation in post-CABG patients.Results:Out of 334 patients, 248 were males and 86 were females with age (54.74 ± 7.61) years old. The total average score of CRBS-C/M in patients after CABG surgery was 3.20 ± 0.43, with the highest external logistic factors score of 3.42 ± 0.58. The knowledge status score of information related to cardiac rehabilitation was 42.11 ± 7.94. Multiple linear regression analysis revealed that the following factors independently influenced post-CABG patients′ barriers to participating in phaseⅡcardiac rehabilitation: marital status, whether or not they had completed phase I cardiac rehabilitation,number of other comorbidities, knowledge of cardiac rehabilitation information. All of these differences were statistically significant ( t values were -4.87-3.35, all P<0.05). Conclusions:The barriers to participation in phase Ⅱ cardiac rehabilitation in post-CABG patients are at an intermediate to high level, and healthcare professionals should emphasize the assessment of barrier factors in these patients, and target the development and implementation of phase Ⅱ cardiac rehabilitation in terms of the influencing factors.

[Objective] To investigate the clinical features and treatment of renal cell carcinoma unclassified with medullary phenotype (RCCU-MP), so as to improve the clinical understanding of this disease. [Methods] The clinical data of 2 patients with pathological diagnosis of renal medullary carcinoma (RMC) in Zhujiang Hospital during 2019 and 2023 were retrospectively analyzed, and relevant literature was reviewed. [Results] Both patients had symptoms of backache, and imaging examination indicated renal space-occupying lesions.Case 1 was diagnosed as RMC by renal biopsy, and case 2 was pathologically diagnosed as RMC after surgery.Both cases lacked evidence of sickle cell trait or sickle cell disease, and were finally diagnosed as RCCU-MP.Case 1 did not receive antineoplastic therapy and died 5 months after diagnosis.Case 2 underwent laparoscopic nephrectomy, and then received gemcitabine + paclitaxel chemotherapy + immunotherapy.The patient's tumor progressed gradually after first-line treatment was abandoned due to concurrent hematologic infection, and he eventually died 7 months after surgery. [Conclusion] The clinical features of RCCU-MP are partially similar to those of RMC.The diagnosis of RCCU-MP requires pathological examinations and should exclude sickle cell trait or sickle cell disease.Due to the aggressive nature of the tumor, the prognosis of patients is poor.

Abstract: Objective　To analyze and understand the mutations of drug resistance genes in imported Plasmodium falciparum in Shenzhen, aiming to assess the efficacy of antimalarial drugs and guide effective drug use. Methods A total of 85 samples from individuals with imported Plasmodium falciparum confirmed by fluorescence quantitative polymerase chain reaction (PCR) in Shenzhen from 2022 to 2023 were collected and genomic DNA was extracted. Nested PCR was used to amplify resistance genes, including Plasmodium falciparum Kelch 13 (PfK13), multidrug resistance gene 1 (Pfmdr1), chloroquine resistance transporter (Pfcrt), dihydrofolate reductase (Pfdhfr), and dihydropteroate synthase (Pfdhps) genes. Bidirectional sequencing was conducted, and mutations in these resistance genes were analyzed using MEGA11.06 software. Results　The study found one missense mutation (S549P) and four synonymous mutations in PfK13. For Pfmdr1, 62.69% of the samples showed Y184F mutation, and no N86Y mutation was detected. No mutations at positions 72 and 73 were detected in the Pfcrt gene, while mutations at M74I, N75E, and K76T accounted for 17.46%, 15.87%, and 15.87%, respectively. The wild-type of Pfcrt gene is dominant (82.54%, 52), followed by the triple mutant I74E75T76 (15.87%, 10). The most common mutation type for Pfdhfr is I51R59N108 (91.78%, 67), followed by the wild type (2.74%, 2). More than half (60.32%, 38) of the Pfdhps samples were wild-type, with single mutation K540E being the most common mutation type. S436A, G437A, K540E, A581G, A613S, I431V, G556K, and G579E site mutations were detected. Among the Pfdhfr-Pfdhps combination mutations, I51R59N108-E540 was the most frequent combination mutation (11.48%), with 59.02% of samples showing solitary Pfdhfr mutations. Conclusions In this study, PfK13 mutation rates were low, with no reported resistance mutations. The Y184F mutation emerged as the dominant Pfmdr1 mutation, with no detection of N86Y. For Pfcrt, the wild-type was dominant, followed by the I74E75T76 triple mutation variant. Triple mutant I51R59N108 of Pfdhfr was very common, and our study did not find Pfdhfr Pfdhps completely resistant and super resistant mutants, but there were other quintuple and septuple mutant types. In the future, it is crucial to continue to strengthen the monitoring of malaria parasite resistance genes and to further integrate in vivo efficacy monitoring to effectively guide clinical drug use.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

In this article, we report a case of spontaneous ruptured pyomyoma during pregnancy with successful delivery after myomectomy. A 35-year-old pregnant female (27 weeks of gestation) presented with lower abdominal pain. The patient had a history of uterine fibroids. Ultrasound, computed tomography, and magnetic resonance imaging confirmed a spontaneous ruptured pyomyoma (maximum diameter: 12.6 cm). Myomectomy was performed, and her abdominal distension and pain were significantly improved within 1 day; the condition of the fetus was normal. One month after surgery, severe tenderness was detected in the lower right side of the uterus. Considering the higher risk of uterine rupture and associated complications, a cesarean section was performed. The mother and neonate were discharged 3 and 42 days after delivery, respectively, in good condition. Myomectomy for spontaneous ruptured pyomyoma during pregnancy may be feasible and extend gestational age to improve outcomes for the mother and neonate.

In this article, we report a case of spontaneous ruptured pyomyoma during pregnancy with successful delivery after myomectomy. A 35-year-old pregnant female (27 weeks of gestation) presented with lower abdominal pain. The patient had a history of uterine fibroids. Ultrasound, computed tomography, and magnetic resonance imaging confirmed a spontaneous ruptured pyomyoma (maximum diameter: 12.6 cm). Myomectomy was performed, and her abdominal distension and pain were significantly improved within 1 day; the condition of the fetus was normal. One month after surgery, severe tenderness was detected in the lower right side of the uterus. Considering the higher risk of uterine rupture and associated complications, a cesarean section was performed. The mother and neonate were discharged 3 and 42 days after delivery, respectively, in good condition. Myomectomy for spontaneous ruptured pyomyoma during pregnancy may be feasible and extend gestational age to improve outcomes for the mother and neonate.