BACKGROUND:Shujin Jiannao Prescription is an empirical formula for the treatment of cerebral palsy in Dongzhimen Hospital,Beijing University of Chinese Medicine,with clear clinical efficacy,but the specific mechanism needs to be elucidated. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into a normal group(n=12)and a model group(n=52).An animal model was established by the Rice-Vannucci method.After successful modeling,52 model rats were randomly divided into control model group(n=12),minocycline group,and the low-,medium-,and high-dose groups of the Shujin Jiannao Prescription(n=10 per group).Rats in the minocycline group were given 40 mg/kg·d minocycline by gavage;rats in the low-,medium,and high-dose groups were given 4,8,and 16 g/kg·d Shujin Jiannao Prescription granules by gavage,respectively;and rats in the normal group and control model group were given an equal dose of normal saline by gavage.Medication in each group was given once a day for 1 week.The rats in each group were evaluated behaviorally using suspension test,abnormal involuntary movement score,and Bederson score.The pathological changes of the cerebral cortex were observed by hematoxylin-eosin staining.The levels of tumor necrosis factor α,interleukin 1β,and interleukin 10 in the cerebral cortex were determined using ELISA.The positive expressions of Janus kinase 2(JAK2),phosphorylated Janus kinase 2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)in the cerebral cortex were detected using immunohistochemistry.The protein expression levels of JAK2,p-JAK2,and p-STAT3 were detected using western blot. RESULTS AND CONCLUSION:Compared with the normal group,the suspension test score and involuntary movement score were decreased in the control model group(P＜0.01 or P＜0.05).The pathological results showed structural disruption of nerve cells,formation of large numbers of vacuoles,cell swelling,and increased intercellular space in the control model group.In addition,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were significantly increased(P＜0.01),the expression of interleukin 10 was decreased(P＜0.05),and the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly increased(P＜0.01)in the control model group compared with the normal group.Compared with the model group,minocycline and Shujin Jiannao Prescription at each dose could improve the behavioral indexes of rats(P＜0.01 or P＜0.05)and ischemic-hypoxic pathological changes were attenuated,with only a small amount of necrotic nerve cells and a few vacuoles,and reduced intercellular space.Moreover,the expressions of tumor necrosis factor α and interleukin 1β in the cerebral cortex were decreased in each drug group compared with the control model group(P＜0.05),while the protein expressions of JAK2,p-JAK2,and p-STAT3 in the cerebral cortex were significantly decreased(P＜0.01).The most obvious improvement was observed in the high-dose Shujin Jiannao Prescription group.To conclude,Shujin Jiannao Prescription can inhibit inflammation in the cerebral cortex of rats with hypoxic-ischemic brain injury.The mechanism may be related to the regulation of the JAK2/STAT3 signaling pathway.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Humans ; Stroke ; Phagocytosis/physiology* ; Inflammation ; Apoptosis/physiology* ; Animals ; Phagocytes/physiology* ; Brain/metabolism* ; Efferocytosis

Humans ; Pulmonary Embolism/etiology* ; Humeral Fractures/surgery*

Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.

Background Dengue fever is a mosquito-borne disease transmitted by Aedes aegypti and Aedes albopictus. Under the background of climate change, there are great challenges in the prevention and control of dengue fever, posing a serious health risk to the population. Objective To analyze the mechanism of temperature on dengue fever transmission and estimate the risk of dengue fever under different climate change scenarios by establishing a coupled human-mosquito dynamics model using Guangzhou as a research site, and to provide reference for adaptation to climate change. Methods Reported dengue fever cases and meteorological data from January 1, 2015 to December 31, 2019 in Guangzhou were collected from Guangdong Provincial Center for Disease Control and Prevention and China Meteorological Data Service Centre, respectively. The temperature data under three Representative Concentration Pahtyway (RCP2.6, RCP4.5, and RCP8.5) scenarios in 2030s (2031–2040), 2060s (2061–2070), and 2090s (2091–2099) were calculated by five general circulation models (GCMs) provided by the fifth phase of the Coupled Model Intercomparison Project. A dengue fever transmission dynamics (ELPSEI-SEIR) model was constructed to analyze the mechanism of temperature affecting dengue fever transmission by fitting the dengue fever epidemic trend from 2015–2019, and then the daily mean temperature under selected RCP scenarios for 2030s, 2060s, and 2090s was incorporated into the established dynamics model to predict the risk of dengue fever under different climate change scenarios in the future. Results From January 1, 2015 to December 31, 2019, a total of 4 234 cases of dengue fever were reported in Guangzhou, including 3741 local cases and 493 imported cases. The regression results showed that the model well fitted the dengue fever cases in Guangzhou from 2015 to 2019, and the coefficient of determination R2 to evaluate goodness of fit and the root mean squared error were 0.82 and 1.96, respectively. A U-shaped or inverted U-shaped relationship between temperature and mosquito habits could directly affect the number of mosquitoes and the transmission of dengue fever. We also found that temperature increase in most future scenarios could promote the transmission of dengue fever, and the epidemic period was significantly wider than the baseline stage. The epidemic of dengue fever would peak in the 2060s under the scenarios of RCP2.6 and RCP4.5. The estimated incidence of dengue fever was predicated to be highest in the 2030s and then decrease in the following years under RCP8.5, and in the 2090s, the incidence would decrease significantly, but the incidence peak would be earlier in each year, mainly from May to July. Conclusion Temperature can directly affect mosquito population and dengue fever transmission by affecting mosquito habits. The cases of dengue fever will increase under most climate scenarios in the future. However, the epidemic risk of dengue fever may be suppressed, and the epidemic season may be advanced under RCP8.5.

Objective:To study the correlation between the acute-phase characteristics of motor evoked potential (MEP) and severities of spinal cord injury in patients with acute cervical hyperextension injury and central cord syndrome (CCS).Methods:Retrospectively analyzed were the data of 45 patients with acute cervical hyperextension injury and CCS (observation group) who had been admitted to Department of Orthopedics, Tongji Hospital Affiliated to Tongji University from December 2018 to July 2021 and 20 healthy controls. Examination of transcranial magnetic stimulation-induced MEP was performed in patients with CCS and healthy controls using a magpro x100 magnetic stimulator, and recording was conducted in bilateral abductor pollicis brevis (APB). The characteristics of MEP waveform latency, amplitude and motor threshold were described and compared between the healthy control and observation groups; the correlations were analyzed between the MEP latency and the severity of spinal cord injury [American Spinal Injury Association (ASIA) total score and motor function of Upper Extremity Motor Subscores (UEMS)] in the observation group. According to different MEP-induced states, the patients in the observation group were divided into a resting group ( n=19), a facilitation group ( n=18), and a no-waveform group ( n=8). The severity of spinal cord injury (ASIA total score) and the functional independence of the spinal cord (SCIM-Ⅲ score) were compared among the 3 groups to analyze the correlation between the MEP-induced state and the severity of spinal cord injury (ASIA total score). Results:The observation group had a significantly longer MEP latency [(30.16±6.32) ms], a significantly smaller amplitude [(0.54±0.30) mV] and a significantly higher motor threshold [(65%±11%)] than the healthy control group (all P<0.05). The MEP latency in the observation group was significantly correlated with ASIA total score ( r=-0.730, P<0.001) and UEMS ( r=-0.740, P<0.001). The ASIA total score and SCIM-Ⅲ score were significantly different among the 3 groups ( P<0.05), and the MEP-induced state was significantly correlated with the severity of spinal cord injury (ASIA total score) ( r=0.668, P<0.001). Conclusions:In patients with acute cervical hyperextension injury and CCS, the MEP latency is prolonged, the amplitude lowered, and the motor threshold enhanced. The MEP latency is strongly correlated with the severity of spinal cord injury and upper limb motor function. The MEP-induced state is also closely related to the severity of spinal cord injury.

Objective:To explore the clinical effects of axillary propeller flaps in reconstructing the axillary fold scar contracture.Methods:A retrospective cohort study was conducted. From July 2016 to January 2020, 11 patients with anterior axillary fold or anterior and posterior axillary fold scar contractures after burns were admitted to Xiangya Hospital of Central South University, including 7 males and 4 females, aged 8 to 48 years. The lesions involved unilateral axilla in 9 cases and bilateral axilla in 2 cases, with the joint abduction angle of the affected shoulder ranging from 25 to 100°. The axillary fold contracture scars were excised and released, resulting in wound of 8 cm×5 cm-24 cm×20 cm. According to the condition of the residual normal skin in axilla, 2, 3, and 4-leaf propeller flaps with area of 5 cm×3 cm-24 cm×10 cm were designed to repair the wounds after scar excision and release. The donor site wound was closed by suturing directly, and the residual wound that could not be completely sutured was transplanted with free full-thickness skin grafts from the inner thigh or abdomen. The application of 2, 3, and 4-leaf propeller flaps, the joint abduction angle of the affected shoulder immediately after operation, and the survival of the flaps and skin grafts after operation were recorded. The recurrence of scar contracture, the appearance of the flaps, the joint abduction angle of the affected shoulder, and the functional recovery of the affected shoulder joint and upper arm were observed through a follow-up.Results:Among the 13 axillary propeller flaps transplanted in the 11 patients in this group, there were 9 double-leaf propeller flaps, two 3-leaf propeller flaps, and two 4-leaf propeller flaps. The joint abduction angle of the affected shoulder reached 110-165° immediately after operation. All the flaps survived after operation. Nine flap donor sites were repaired with free skin grafts, with skin grafts survived in 7 flap donor sites after operation. Scar erosion in incision and small area of skin graft necrosis developed in 2 flap donor sites. One of the wounds was debrided and repaired by transplantation of split-thickness skin grafts from inner thigh, and the other wound was healed after dressing changes. A follow-up of 6 to 24 months was conducted after surgery, and all the patients had no recurrence of axillary scar contracture; the color of the flap matched the receiving area; the elasticity of flap was good; the joint abduction angle of the affected shoulder reached 120-165°, and the joint pronation and supination, upper arm lifting and circular rotation of the affected shoulder were all good.Conclusions:Reconstruction of the axillary fold scar contracture with axillary propeller flaps has good result, with better flap appearance and recovery of the shoulder joint activity and upper arm function after operation.

Objective:To evaluate the efficacy and long-term effect of functional electrical stimulation (FES) on cerebral palsy. Methods:Literature retrieval was carried out in the electronic databases of PubMed, Embase, Web of Science, Cochrane Library, China Biology Medicine Disc (CBM), CNKI, Wanfang Database and VIP. The time limit was from the establishment of these databases to March 26th, 2020. According to the inclusion and exclusion criteria, randomized controlled trials about FES for children with cerebral palsy were included. At least two evaluators extracted the data independently and used Cochrane 5.1.0 bias risk assessment tool to evaluate the quality of included studies. The data was analyzed with Review Manager 5.3 software. Results:A total of eleven studies with 513 children were included. The Gross Motor Function Measure-88 (GMFM-88) D/E scores (MD = 8.14, 95%CI 6.26 to 10.02, P < 0.001), GMFM-88 B score (MD = 8.77, 95%CI 4.00 to 13.53, P < 0.001), modified Ashworth Scale (MAS) score (MD = -1.05, 95%CI -1.25 to -0.84, P < 0.001), Kyphosis angle (MD = -10.67, 95%CI -12.21 to -9.13, P < 0.001), Cobb's angle (MD = -2.66, 95%CI -3.38 to -1.93, P < 0.001), step length (MD = 3.35, 95%CI 1.81 to 4.90, P < 0.001), walking speed (MD = 0.09, 95%CI 0.05 to 0.14, P < 0.001) and GMFM score at six weeks follow-up (MD = 4.84, 95%CI 1.90 to 7.77, P = 0.001) were better in FES group than in the control group. There was no significant difference in MAS score between two groups after six weeks of follow-up (MD = 0.04, 95%CI -0.30 to 0.37, P = 0.84). Conclusion:FES could improve the lower-limb and trunk function of children with cerebral palsy, however, the long-term effect of relieving muscle spasm was not significant.

Objective:To study and compare the prognosis of different pathological subtypes of renal cell carcinoma (RCC).Methods:Clinicopathological and prognostic data of 1 346 cases of postoperative renal cell carcinoma during July 2002 to June 2014 in West China Hospital were collected retrospectively.There were 839 males and 507 females, aged (55.1±13.4)years, including 1 120 cases of clear cell RCC, 62 cases of papillary RCC, 79 cases of chromophobe RCC and 85 cases of the other pathological types respectively. ECOG 0 and ≥1 were 911 and 435 cases, with; T 1, T 2, T 3 and T 4 of 1 019, 177, 102 and 48 cases respectively; WHO nuclear grade for well, intermediate, poor differentiation and unknown were 587, 530, 85 and 144 cases separately.Tumor size <5cm, 5-10cm, ≥10cm and unknown were 685, 541, 104 and 16 cases.Combined with necrosis or sacromatoid differentiation were 200/1 146 and 27/1 319 cases separately. Meanwhile, data of 80 439 cases from Surveillance, Epidemiology, and End Results Program (SEER) were also collected.There were 51 371 males and 29 068 females, aged (60.9±12.4) years; , with 66 261, 8 680, 5 022 and 476 cases of White, Black, Asian, American native, or unknown race separately. There were 62 600 of clear cell RCC, 12 170 of papillary RCC, 4 354 of chromophobe RCC and 1 315 of other pathological types, with T 1, T 2, T 3 and T 4 of 55 332, 8 687, 15 516 and 904 cases respectively; WHO nuclear grade for well, intermediate and poor differentiation were 52 323, 22 700 and 5 416 cases separately.Tumor size <5cm, 5-10cm, ≥10cm were 46 741, 25 760 and 7 938 cases respectively. Kaplan-Meier survival analysis were performed on these two group of cases, with different factors between subgroups (gender, age, pathological types, tumor stage, size and nuclear grade) evaluated by log-rank test. To evaluate accuracy of outcome prediction models of SSIGN, Leibovich and UISS score, concordance index of these models were evaluated. Results:In 1 346 cases of our cohort, those with chromophobe RCC were well prognostic, survival were relatively better in clear cell RCC than that of papillary RCC, and worst prognosis were demonstrated in those with other types of RCC (5 year overall survival rate: 97.5%, 87.9%, 79.7% and 68.4% separately). Poor prognosis were seen in those older than 50 years, with poor T stage or nuclear grade, large tumor size and tumors with necrosis or sacromatoid differentiation ( P<0.05). In 80 439 seer cases, the best prognosis was also seen in chromophobe RCC and the worst in other type of RCC separately (5 year overall survival rate: 96.3% and 85.3%). In addition, longer survival was seen in papillary RCC than clear cell RCC (5 year overall survival rate: 92.5% and 88.9%). However, similar results with our cohort were seen in Asian and American native subgroup of SEER cases (95.1%, 88.6%, 86.7%, 80.2% for chromophobe, clear cell, papillary and other types of RCC respectively). Poor prognosis were seen in those older than 50 years, males, Asian/ American Indian, poor T stage or nuclear grade and large tumor size ( P<0.05). Concordance index for SSIGN, Leibovich and UISS models in our cohort were 0.763-0.781, 0.725-0.752 and 0.641-0.660, respectively. The chromophobe RCC subgroup was relative better based on predictive value of prognosis models(c-index of UISS of 0.670-0.781, SSIGN and Leibovich of 0.733-0.903). Conclusions:In Asian RCC population, prognosis of chromophobe RCC is best, clear cell RCC is slightly better than papillary RCC, and the prognosis of other types of RCC is the worst. Concordance index of SSIGN and Leibovich in our cohort were higher than that of UISS, and the use value for predictive model was better in the chromophobe RCC subgroup.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.