Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

Objective:To evaluate the design and application of the superior thyroid artery perforator flap (STAPF) for reconstruction after head and neck oncological resection.Methods:A retrospective analysis was performed on 24 consecutive patients (22 men, 2 women; age 40-72 years) treated at Hunan Cancer Hospital between June 2018 and December 2023. Their primary tumors included buccal carcinoma ( n=7), tongue carcinoma ( n=8), oropharyngeal carcinoma ( n=2), floor-of-mouth carcinoma ( n=3), laryngeal carcinoma ( n=3), and hypopharyngeal carcinoma ( n=1). Flap design, venous drainage strategy, and postoperative outcomes were assessed. SPSS 19.0 software was used for statistical analysis. Results:Flap dimensions were length of 9.4±0.5 cm, width of 3.3±0.6 cm, thickness of 0.5±0.2 cm, and pedicle length of 7.3±0.6 cm. Fifteen flaps were based on a single perforator (diameter ≥0.5 mm), whereas, nine fascial flaps incorporated multiple perforators (capillary diameter ≤0.5 mm). Venous drainage routes were as follows: superior thyroid vein ( n=12, retrograde in 3), facial vein ( n=5, all retrograde), anterior jugular vein ( n=4, retrograde in 1), and external jugular vein ( n=3, retrograde in 2). All 24 flaps survived completely. Donor sites were closed primarily and all cervical wounds healed. No flap-related complications, inculding orocutaneous, pharyngocutaneous, laryngocutaneous fistula and wound infection, were observed. Final pathologic stages were T1N0M0 ( n=2), T2N0M0 ( n=16), T2N1M0 ( n=3), and T3N0M0 ( n=3). With follow-up of 12-46 months, aside from one patient with tongue cancer died of contralateral cervical and parapharyngeal lymph-node metastases at 6 months, others remained disease-free. Patients with laryngeal or hypopharyngeal carcinoma had their tracheostomy tubes removed within 4 weeks postoperatively. Conclusion:STAPF offers flexible design, with minimal donor-site morbidity and low functional impairment. It is particularly advantageous for reconstruction of small-to-moderate defects following head and neck tumor ablation.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

OBJECTIVE To observe the effect of acupuncture combined with a modified Zhengan Xifeng Decoction on the early clinical symptoms and oxidative stress status of patients with hypertensive intracerebral hemorrhage(HICH)of liver-kidney yin defi-ciency syndrome.METHODS A total of 60 patients with hypertensive intracerebral hemorrhage(liver-kidney yin deficiency syn-drome)who successfully received 24-hour acute-phase treatment at the Department of Neurosurgery,Acupuncture and Rehabilitation Department,and wards of Kunshan Hospital Affiliated to Nanjing University of Chinese Medicine(Kunshan Traditional Chinese Medi-cine Hospital)from July 2021 to January 2023 were recruited.A randomization table generated by SPSS 22.0 software was used to di-vide the patients into a control group and an observation group,with 30 patients in each group.The control group received symptomatic treatment,conventional rehabilitation training,and modified Zhengan Xifeng Decoction,while the observation group received additional acupuncture treatment on the basis of the control group.The treatment course was 1 month for both groups.Clinical effective rate,TCM syndrome scores,motor and neurological function scores[Activity of Daily Living(ADL)scale,National Institutes of Health Stroke Scale(NIHSS),Modified Ashworth Scale(MAS),Simplified Fugl-Meyer Assessment(FMA)scale],improvement in hematoma lesions,Fraction anisotropy(FA)ratio(rFA),and serum levels of antioxidant stress response factors Kelch-like ECH-associated protein 1(Keap1)and nuclear factor-E2-related factor 2(Nrf2)were observed before and after treatment in both groups.RESULTS After treat-ment,the clinical effective rate in the observation group was significantly higher than that in the control group(P<0.05);the TCM syn-drome scores in both groups decreased significantly(P<0.05),with the observation group showing better results than the control group(P<0.05);the ADL and FMA scores in both groups reduced significantly(P<0.05,P<0.01),while the NIHSS and Ashworth Scale scores increased significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);serum Keap1 levels decreased significantly in both groups(P<0.01),while Nrf2 levels enhanced significantly(P<0.05,P<0.01),with the observation group showing better improvement than the control group(P<0.05);imaging studies showed that after treat-ment,the residual hematoma volume decreased significantly in both groups(P<0.05,P<0.01),and the rFA value increased signifi-cantly(P<0.05,P<0.01),with the observation group showing better results than the control group(P<0.01).CONCLUSION On the basis of standard treatment for the acute phase,acupuncture combined with Zhengan Xifeng Decoction can significantly improve the early clinical symptoms of HICH patients with liver-kidney yin deficiency,reduce oxidative stress levels,and promote the recovery of nerve and motor functions.

Objective:To evaluate the design and application of the superior thyroid artery perforator flap (STAPF) for reconstruction after head and neck oncological resection.Methods:A retrospective analysis was performed on 24 consecutive patients (22 men, 2 women; age 40-72 years) treated at Hunan Cancer Hospital between June 2018 and December 2023. Their primary tumors included buccal carcinoma ( n=7), tongue carcinoma ( n=8), oropharyngeal carcinoma ( n=2), floor-of-mouth carcinoma ( n=3), laryngeal carcinoma ( n=3), and hypopharyngeal carcinoma ( n=1). Flap design, venous drainage strategy, and postoperative outcomes were assessed. SPSS 19.0 software was used for statistical analysis. Results:Flap dimensions were length of 9.4±0.5 cm, width of 3.3±0.6 cm, thickness of 0.5±0.2 cm, and pedicle length of 7.3±0.6 cm. Fifteen flaps were based on a single perforator (diameter ≥0.5 mm), whereas, nine fascial flaps incorporated multiple perforators (capillary diameter ≤0.5 mm). Venous drainage routes were as follows: superior thyroid vein ( n=12, retrograde in 3), facial vein ( n=5, all retrograde), anterior jugular vein ( n=4, retrograde in 1), and external jugular vein ( n=3, retrograde in 2). All 24 flaps survived completely. Donor sites were closed primarily and all cervical wounds healed. No flap-related complications, inculding orocutaneous, pharyngocutaneous, laryngocutaneous fistula and wound infection, were observed. Final pathologic stages were T1N0M0 ( n=2), T2N0M0 ( n=16), T2N1M0 ( n=3), and T3N0M0 ( n=3). With follow-up of 12-46 months, aside from one patient with tongue cancer died of contralateral cervical and parapharyngeal lymph-node metastases at 6 months, others remained disease-free. Patients with laryngeal or hypopharyngeal carcinoma had their tracheostomy tubes removed within 4 weeks postoperatively. Conclusion:STAPF offers flexible design, with minimal donor-site morbidity and low functional impairment. It is particularly advantageous for reconstruction of small-to-moderate defects following head and neck tumor ablation.

Objective To investigate the effects of miR-4531/CX3CL1 signaling pathway on the vascular injury in preeclampsia, and to search possible targets for early diagnosis and prevention of preeclampsia. Methods Placental tissue samples were obtained from 10 patients with late-onset preeclampsia and 10 normal pregnant women in the Obstetrics and Gynecology Department of Minhang Hospital, Fudan University from October 2021 to December 2022. The levels of miR-4531 and CX3CL1 were evaluated by qRT-PCR. Cell transfection was performed by lipofectamine 2000 in vitro. The binding relationship between miR-4531 and CX3CL1 was determined by luciferase reporter assay. The apoptosis of neutrophils, the migration, repair, colony formation and cell-free DNA (cfDNA) release of human umbilical vein endothelial cells (HUVECs) were detected. Results MiR-4531 was significantly downregulated, and CX3CL1 was upregulated in placental tissues of preeclampsia patients (P＜0.05). Luciferase report assay confirmed the direct binding relationship between miR-4531 and CX3CL1. Upregulation of miR-4531significantly promoted the migration, proliferation, repair, and inhibited cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). However, downregulation of miR-4531 obviously inhibited the proliferation, migration, repair, and enhanced cfDNA release of HUVECs and neutrophils apoptosis in medium under hypoxic condition (P＜0.05). Conclusions The miR-4531is downregulated in placental tissues of preeclampsia parients and is a potential therapeutic target for preeclampsia. It might cause endothelial damage and an abnormal hypercoagulable state under hypoxic condition by targeting and regulating the CX3CL1 pathway.

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.

Objective To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle frac-tures in children.Methods A systematic search was conducted in PubMed,Embase,the Cochrane library,Web of Science,China National Knowledge Internet(CNKI),Wanfang Datebase from in ception to February 2022.Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included.Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality,their excellent and good rate of fracture healing,malunion,delayed union or nonunion,infection,limitation of elbow flexion or extension(＞10°)were ex-tracted and analyzed using software Rev Man 5.3.Results A total of 9 retrospective studies involving 647 patients were includ-ed,with 255 patients in the screw fixation group(including screw combined with Kirschner wire)and 392 patients in the Kirschner wire fixation group.Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[OR=0.22,95％CI(0.09,0.56),P=0.001].There were no significant differences between the 2 groups in excellent and good rate of fracture healing,malunion rate(P＞0.05).Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[OR=0.18,95％CI(0.05,0.65),P=0.009].Conclusion For lateral humeral condyle fractures,Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation.There were no significant differences in the excellent and good rate of fracture healing,malunion.In terms of postoperative efficacy and safety of internal fixation,orthopaedic surgeons are more like-ly to recommend screws for fixation of lateral humeral condyle fractures in children.