Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L⁻¹ permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L⁻¹ permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L⁻¹ permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L⁻¹ permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L⁻¹ permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L⁻¹ compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L⁻¹ permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L⁻¹ permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L⁻¹ permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L⁻¹ permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Objective:To evaluate the clinical efficacy of Xiaoqinglong Decoction Granules in the treatment of chronic persistent cold syndrome of bronchial asthma; To explore its treatment mechanism.Methods:A randomized double-blind controlled study was performed. Totally 60 patients from the Respiratory Department of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine from January 2021 to January 2022 were selected as the observation subjects. They were divided into two groups using a random number table method, with 30 cases in each group. The control group was given conventional treatment plus placebo, and the experimental group was given conventional treatment plus Xiaoqinglong Decoction Granules. The treatment for both group lasted for 14d. TCM syndromes and clinical symptoms before and after treatment were scored. Asthma Control Test Questionnaire (ACT) was used to evaluate asthma control status, and the Asthma Quality of Life Questionnaire (Mini AQLQ) was used to evaluate the physiological and psychological effects of asthma on patients; FEV1 was detected using a German Jaeger lung function instrument FEV1/FVC. A exhaled nitric oxide (FeNO) detection instrument was used to observe the changes in FeNO at a flow rate of 50 ml/s, and non-targeted metabolomics analysis was performed using liquid chromatography-mass spectrometry (LC-MS); adverse reactions were observed during treatment and drug safety was evaluated.Results:Eventually 47 cases were included, 24 cases of test group and of 23 cases of control group. Xiaoqinglong Decoction Granules could reduce the TCM syndrome score of patients with chronic duration cold syndrome of asthma ( P<0.05). 2 weeks after treatment, follow up for 4 weeks experimental group clinical symptom score [3.00(1.00,4.00),3.00(0.00,4.00) vs. 3.5(3.00,5.00), Z=8.62], breathing symptom scores [1.00(0.00,1.00),1.00(0.00,1.00) vs. 1.00(0.75,2.00), Z=6.80], cough symptom score [0.50(0.00,1.00),1.00(0.00,1.00) vs. 1.00(0.00,1.25), Z=6.12] were lower than those in the experimental group before treatment in the same group ( P<0.01 or P<0.05). The ACT score of the experimental group at 4 weeks of follow-up was [22.50 (21.00, 24.00) vs. 9.00 (15.00, 21.50), Z=-4.87], Mini AQLQ score (78.5 ± 12.46 vs. 71.27 ± 9.70, t=-2.46) and the control group had an ACT score of [24.00 (19.00, 25.00) vs. 21.5 (8.00, 23.00) Z=-3.18] at 4 weeks of follow-up was higher than before treatment in the same group ( P<0.01 or P<0.05). The experimental group was followed up for 4 weeks with a FEV1 of [2.96 (2.27, 3.49) L vs. 2.60 (2.32, 3.49) L, Z=-3.72], FEV1/FVC [(80.83 ± 6.84)% vs. (77.46 ± 8.15)%, t=-2.32] and FeNO [24.00 (12.50, 31.00) ppb vs. 30.00 (17.00, 91.00) ppb, Z=-3.72] was higher than before treatment in the same group ( P<0.01 or P<0.05). Through LC-MS technique analysis, there were 75 kinds of different metabolites between the experimental group before and after treatment, and 295 kinds of different metabolites between the control group and the experimental group after treatment. Further intersection of differential metabolites showed that they were mainly concentrated in histidine metabolic pathway, phosphonate metabolic pathway and phosphate metabolic pathway. Related metabolites 2-aminoethyl phosphonate and thiomalonic acid were involved. Conclusions:Xiaoqinglong Decoction Granules can effectively improve the TCM syndrome and clinical symptoms of patients with chronic persistent cold syndrome of asthma, especially for wheezing, cough and chest tightness, which can improve the levels of FEV1 and FEV1/FVC in patients and effectively reduce FeNO. Through metabolomics studies, it is speculated that Xiaoqinglong Decoction Granules may play a role in the treatment of asthma by regulating histidine metabolism pathway through thiomalonic acid.

OBJECTIVE: To investigate the effectiveness of sequential plate internal fixation in the correction of Madelung deformity after ulnar osteotomy and shortening. METHODS: The clinical data of 13 patients with Madelung deformity admitted between September 2015 and July 2021 were retrospectively analyzed. There were 5 males and 8 females with an average age of 18.3 years ranging from 17 to 23 years. The disease duration ranged from 12 to 24 months, with an average of 17 months. Three cases had a clear history of trauma. All patients had external radial deviation deformity and limited movement of the ulnar deviation, and the ulnar impact pain was significant during ulnar deviation movement; 9 patients had limited wrist joint supination movement, and the supination movement was normal. In the first stage, ulnar osteotomy and shortening combined with external fixator were used to correct wrist deformity in 13 patients. After operation, bone transfer was performed 6 times per day, with adjustments made every 4 hours, which was 1 mm per day. After the osteotomy was in place, the ulnar plate internal fixation was performed to reconstruct the ulnar stability in the second stage. The Cooney wrist joint score was used to assess the pain, function, range of motion, flexion and extension range of motion, and grip strength of the wrist joint before operation and before the removal of internal fixator. The subjective feeling and appearance satisfaction of patients were recorded. RESULTS: After the second-stage operation, all the 13 patients were followed up 10-22 months, with an average of 15 months. The deformity of wrist joint disappeared after operation, and the flexion, extension, and ulnar deviation were basically normal. There was no complication such as ulnar impingement sign, nonunion or infection. Wrist function, pain, and range of motion were significantly improved after operation, except for 1 patient who had no significant improvement in rotation and pain. The ulnar internal fixator was removed at 10-18 months after the second-stage operation. The scores of pain, function, range of motion, flexion and extension range of motion, and grip strength in the Cooney wrist score before removal of internal fixator significantly improved when compared with those before operation ( P<0.05). Subjective and appearance satisfaction of patients were excellent in 9 cases, good in 3 cases, and fair in 1 case. CONCLUSION Ulnar osteotomy and shortening with sequential plate internal fixation for correction of Madelung deformity, with mild postoperative pain, can effectively avoid bone nonunion, improve wrist joint function, and have significant effectiveness.
Male ; Female ; Humans ; Adolescent ; Retrospective Studies ; Ulna/surgery* ; Osteochondrodysplasias ; Radius Fractures/surgery* ; Wrist Joint/surgery* ; Osteotomy ; Range of Motion, Articular ; Treatment Outcome

Objective:To explore the curative effect of wide pedicled with double-vessel flap of posterior lateral calf in repair of soft tissue defect in hind foot.Methods:From January 2018 to June 2021, 12 patients with soft tissue defects on hind foot were reconstructed with double-vessel flaps pedicled perforator of peroneal artery and sural nerve nutrient vessels in the Department of Trauma Orthopaedics, No.940 Hospital of Chinese People's Liberation Army Joint Service Support Force. The patients were 8 males and 4 females, aged 9-45(27.17±12.14) years old. Time after injury to admission was 6-24(10.17±4.80) hours. Six patients were with simple soft tissue defects, 2 with tendon defects, 3 with bone defects and 1 with postoperative infection due to an open fracture. The sizes of soft tissue defect ranged from 4 cm×5 cm-8 cm×12 cm. Soft tissue defects were reconstructed by transfer of posterolateral calf flaps, and the bone defects were repaired by phase I or phase II bone grafts or antibiotic cement and membrane induction according to the wound surface. For larger bone defects, stage-II bone transport was carried out to restore the length of the hind foot. Defects of Achilles tendon were reconstructed by direct suture or tendon transposition. Foot functions were evaluated by American Orthopaedic Foot and Ankle Surgery(AOFAS) ankle-posterior sufficient scale, visual analogue scale(VSA) score and flap healing. All patients were included in postoperative follow-up regularly through outpatient clinic or via WeChat.Results:All 12 patients had postoperative follow-up that lasted for 6-24(12.92±6.22) months. One flap developed dark purple colour with swelling at the distal end of the flap 3 days after surgery. It eventually healed after removed some sutures from the pedicle together with blood-letting on the flap surface. Three flaps developed local infection, and they were cured after debridement, dressing change and the use of sensitive antibiotics. The remaining 8 patients had achieved good appearance of flaps and normal ankle function. According to AOFAS, scores of ankle-posterior sufficiency scale increased from 14-45(25.25±5.42) before surgery up to 65-96(75.92±7.73) at the final follow-up. Of the 12 patients, 8 were in excellent, 2 in good and 2 in fair. The VAS scores decreased from 5-8(6.55±1.13) before surgery down to 0-4(1.55±1.37) at the final follow-up. The difference had statistics significance( P<0.01). All patients had satisfactory recovery of ankle function, with the extension at 15-20 degrees and plantar flexion of 30-40 degrees. The donor site healed well and all skin grafts survived. Conclusion:The double-vessel flap pedicled with perforating branch of peroneal artery and nutrient vessels of sural nerve can be used for reconstruction of soft tissue defect of hind foot. It achieved good surgical effects with reliable blood supply, smooth venous return, strong anti-infection ability, satisfactory appearance at donor site and flap itself, as well as a good recovery of foot function.

Objective:To observe and analyze the changes and correlation of macular mean sensitivity (MS) and the thickness of ganglionic plexiform layer (GCIPL) in patients with non-arteriotic anterior ischemic optic neuropathy (NAION).Methods:A cross-sectional clinical study. From March to August 2023, 37 patients with 38 eyes of NAION (NAION group) diagnosed by ophthalmic examination in the First Affiliated Hospital of Zhengzhou University were included in the study. In the NAION group, 29 patients with contralateral healthy eyes were selected as the contralateral healthy eye group. A total of 31 eyes of 16 healthy subjects matching gender and age were selected as the normal control group. NAION group was divided into acute stage group (disease course ≤3 weeks), subacute stage group (disease course 4-12 weeks) and chronic stage group (disease course>12 weeks), with 16, 10 and 12 eyes, respectively. Best corrected visual acuity (BCVA), optical coherence tomography (OCT), perimetry, and microperimetry were performed. BCVA statistics are converted to logarithm of the minimum angle of resolution (logMAR). The macular region was scanned by Cirrus HD-OCT macular volume 512×128 scanning program. The mean (GCIPLav), minimum (GCIPLmin), and the GCIPL thickness at supranasal, superior, subnasal, supratemporal, inferior, and inferotemporal quadrants were detected. The Humphrey 24-2 automated visual field test was utilized to measure the mean defect (MD) of the visual field. MP-3 microperimetry was used to measure MS (total MS) in the 10° macular region and MS in the supranasal, superior, subnasal, supratemporal, inferior, and inferotemporal quadrants. MS> 21 dB was defined as normal. One-way analysis of variance was used to compare among groups. t test was used to compare GCIPL thickness between MS≤21 dB and> 21 dB regions. Spearman correlation analysis was used to analyze the correlation between GCIPL thickness and MS in corresponding areas. Results:There were statistically significant differences in logMAR BCVA and MS in the NAION group, contralateral healthy eye group, and normal control group ( F=13.595, 83.741; P<0.05). GCIPL thickness in the MS≤21 dB region was significantly lower than that in the> 21 dB region in the NAION group ( t=2.634, P=0.009). The thickness of GCIPL in the inferotemporal quadrant decreased in the NAION group compared with the contralateral healthy eye group and normal control group, but the difference was not statistically significant ( P=0.092, 0.192). The thickness differences of GCIPLav and GCIPLmin and GCIPL in other quadrants were statistically significant ( P<0.05). Compared with the contralateral healthy eye group and normal control group, the thickness of GCIPLmin, superior and supratemporal of GCIPL in the acute stage group were significantly decreased ( P<0.05). The thickness of GCIPLav, GCIPLmin, GCIPL in upranasal, superior and supratemporal quadrants were significantly decreased in the subacute stage group ( P<0.05). The thickness of GCIPLav, GCIPLmin and GCIPL in all quadrants were significantly decreased in the chronic stage group ( P<0.05). Correlation analysis showed that total MS were significantly correlated with logMAR BCVA ( r=0.779, -0.596, P<0.001) in NAION group. The inferior GCIPL thickness was significantly correlated with MS in the corresponding region ( r=0.410, P=0.046), while no correlation was found in the other quadrants ( r=0.220, 0.148, -0.131, 0.296, 0.321; P>0.05) in NAION group. GCIPL thickness in acute and subacute groups was significantly correlated with MS ( r=0.329, 0.400; P=0.007, 0.028). There was no correlation in the chronic phase group ( r=0.238, P=0.103). Conclusions:GCIPL atrophy and thinning and MS decrease in the macular area of NAION. The thickness of GCIPL in the MS decreasing region is significantly lower than that in the MS normal region. GCIPL atrophy and thinning in acute and subacute stages are correlated with MS.

Objective:To investigate the clinical efficacy of Jinghua Weikang capsule combined with Bifidobacterium for curing patients featured by spleen-stomach damp-heat syndrome and Helicobacter pylori (Hp) infection with low DOB values.Methods:To enroll 130 cases who were admitted to the Digestion Center of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from March 2019 to March 2020. According to the treaatment protocols, the quadruple therapy group and dual therapy group, each had 65 patients. The quadruple therapy group had two different treatment protocols, 34 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Clarithromycin, the other one had 31 cases with Rabeprazole sodium enteric-coated tablet, Bismuth potassium citrate capsule, Amoxicillin capsule, and Levofloxacin tablets. The Dual therapy group was treated with Jinghua Weikang capsule combined with Bifidobacterium. As for quadruple therapy group, 14 days was a course of treatment, while28 days was a course of treatment for dual therapy group. The two groups were treated for one course, respectively. The TCM syndromes were scored before and after treatment. After 4-weeks long drug withdrawal, all cases were reexamined via 13C-UBT. The Hp eradication rate, efficacy evaluation and adverse reactions were compared between both groups.Results:The eradication rate was 90.8% (59/65) in quadruple therapy group and 78.5% (51/65) in dual therapy group. There was no statistical difference between two groups ( χ２=3.78, P=0.052). As for quadruple therapy group, the eradication rate was 91.2% (31/34) in Protocol One and 90.3% (28/31) in Protocol Two. There was no statistical difference between two protocols ( χ２=0.01, P=0.906). After treatment, the TCM syndrome score of quadruple therapy group [(7.02±0.89) vs. (6.51±0.85), Z=-3.01], was significantly higher than that of dual therapy group ( P<0.01). The total effective rate was 93.9% (61/65) in dual therapy group and 78.5% (51/65) in quadruple therapy group. There was statistically significantly difference between two groups ( χ２=6.45, P=0.011). The adverse reactions was 24.6% (16/65) in quadruple therapy group and 6.2% (4/65) in dual therapy group. There was statistically significantly difference in two groups ( χ２=8.51, P=0.004). Conclusions:The Jinghua Weikang capsule combined with Bifidobacterium had curative effects on Hp infected patients with low DOB values. It could improve TCM Syndromes with little adverse reactions.

Objective:To investigate the effects of anterolateral wide pedicled double dynamic flap of the calf in repair of soft tissue defects of mid-and forefoot.Methods:From September 2015 to Septemler 2020, 15 cases with severe soft tissue defects of mid-and forefoot were repaired with the anterolateral wide pedicled double dynamic flap of the calf. There were 11 males and 4 females with an average age of 37(range, 22-53)years old. Of the 15 cases, the defects were caused by traffic accident in 6 cases and objects smash in 9 cases. Three cases were simple soft tissue defect, and 12 cases combined with fracture or dislocation and bone defect. The size of soft tissue defects ranged from 4 cm×5 cm to 7 cm×12 cm. All wounds of donor sites were repaired by skin grafting. All patients entered follow-ups at the outpatient clinic or through WeChat. The appearance of flaps and limb recovery were recorded after surgery.Results:All cases followed-up for 6-24 (mean, 16) months. Two days after surgery, 1 case had flap swelling and cyanosis, which was improved after pedicle suture removal and surface bloodletting. The pedicle of the flap was slightly bloated in 4 cases, and the texture and appearance were good in 11 cases. The ankle function of all cases recovered satisfactorily. The ranges of ankle motion were 15°-20° for dorsiflexion and 30°-40° for plantar flexion. The donor site healed well and all the skin grafts survived.Conclusion:The anterolateral wide pedicled double dynamic flap of the calf is one of the ideal flaps for repairing the soft tissue defects of the mid-and forefoot with reliable blood supply, sufficient venous return, simple operation and no require a vascular anastomosis.

Objective:To evaluate the safety and validity of enriched autologous bone marrow mesenchymal stem cells (BMSCs) and annular suture for repairing defect after lumbar discectomy.Methods:Enrichment of autologous BMSCs: autologous bone marrow blood was collected from 5 patients undergoing lumbar surgery, and nucleated cells were enriched on gelatin sponge particles by selective cell retention technique. From October 2016 to March 2019, 109 patients with lumbar disc herniation underwent discectomy with mobile microendoscopic discectomy technique, including 61 males and 48 females, aged 24-59 years. Discectomy group: 26 cases received simple discectomy. Suture group: 39 cases received annular suture after discectomy. BMSCs+suture group: 44 cases received intradisc transplantation of gelatin sponge particles enriched with autologous BMSCs and annular suture after discectomy. The perioperative conditions were recorded, with visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pfirrmann grade of disc degeneration, disc height and degree of herniationevaluated after operation.Results:In enrichment test with flow cytometry, the enrichment multiple of nucleated cells and target cells was 6.4±0.9 and 4.2±0.6 respectively, and BMSCs grew well in vitro. The operation time was 35-55 mins. 7 cases in the suture group were transferred to the discectomy group and 10 cases in the BMSCs+suture group were transferred to BMSCs group due to unsuccessful suture. There were no significant differences in VAS, ODI, Pfirrmann grade of disc degeneration, disc height and degree of herniation among the groups. There was no significant difference in intraoperative bleeding, postoperative drainage and length of hospital stay. The incision was healed without redness and swelling. 18 patients were followed up for 6 months, and 91 cases were followed up for 1-3 years (25.0±5.6 months). There was no interbody fusion, heterotopic ossification or infection during follow-up. VAS and ODI decreased significantly after operation in all patients. At final follow-up, the VAS improvement rate of BMSCs+suture group (81.7%±7.9%) was higher than discectomy group (73.0%±8.9%), suture group (74.0%±6.9%) and BMSCs group (75.3%±8.4%); the ODI improvement rate of BMSCs+suture group (91.9%±8.8%) was higher than discectomy group (86.2%±8.1%) and suture group (86.4%±5.5%). According to MRI, the Pfirrmann grade of disc increased 0.7 in discectomy group, 0.6 in suture group, while it did not increased significantly in BMSCs+suture group and BMSCs group, and the progress of Pfirrmann grade in BMSCs+suture group and BMSCs group were lighter than discectomy group and suture group.The disc height decreased in each group, the loss rate of disc height in BMSCs+suture group (17.2%±4.3%) was less than discectomy group (29.3%± 6.3%) and suture group (20.6%±5.7%); and suture group was less than discectomy group. The degree of herniation was reduced by more than 50% in all groups, while 1 case in discectomy group had herniation without clinical symptoms.Conclusion:Autologous BMSCs and annulus suture are safe and effective in repairing the defect after lumbar discectomy, which may help to slow down the degeneration of intervertebral disc.

Objective:To study the clinical characteristics of double aortic arch (DAA) combined with aortoesophageal fistula (AEF), and summarize the diagnosis and treatment experience.Methods:Retrospective analysis was performed on the diagnosis and treatment of a newborn with hemorrhagic shock caused by DAA combined with AEF in the Guangzhou Women and Children's Medical Center. The key searching words included "double aortic arch", "aortoesophageal fistula", "vascular ring", "newborn or neonate", and "infant, newborn". The relevant reports were retrieved from databases of CNKI, Wanfang, VIP, PubMed, Springer Link, Google Scholar, Web of Science, Embase, Cochrane Library and OVID, to summarize the clinical features, diagnosis and treatment experience of neonates with DAA and AEF. The retrieval deadline was December 31, 2020.Results:A full-term female newborn was hospitalized for dyspnea immediately after birth, and failed to evacuate from the ventilator for several times. The patient was fed with nasogastric tube and transferred to our hospital because of hemorrhagic shock occurring in 32 days after birth, and gastrointestinal bleeding occurred repeatedly with the maximum bleeding volume reaching 200 ml/time. DAA was diagnosed by cardiac ultrasound and CT, AEF hemorrhage was finally confirmed by gastroscopy, aortography and operation. DAA correction and esophagus repair were successfully performed, and the infant recovered well after the operation. At 9-month old, the infant grew and developed well. At present, no reports of DAA combined with AEF neonates have yet to be published in medical literatures in China. Seven English language literatures included 7 cases of AEF complicated with DAA in neonatal period, 5 cases survived and 2 cases died have so far been reported. All patients have a long history of gastric tube indwelling.Conclusions:The incidence of DAA combined with AEF is rare in the newborn with respiratory and swallowing difficulties as the first manifestation. The disease symptoms progressed rapidly, and life-threatening digestive tract hemorrhage may occur, which often requires surgical treatment. Prolonged gastric tube retention should be avoided in DAA children to prevent the occurrence of AEF.