Aim To investigate the effeot of Shenqi Fuzheng injection on the prevention of immune myocarditis induced by anti-PD-1 antibody by reducing the production of inflammatory factors and the expression of myocardial injury markers. Methods Thirty-two maie PD-1 humanized mice with C57BL/6 genetic background were randomly divided into control group, myocarditis model group, anti-PD-1 antibody group and Shenqi Fuzheng injection group (n = 8). Except the control group, mice in other groups were intraperitoneally injected with myocardial myosin heavy chain peptide (5 mg • kg

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
Humans ; Mice ; Animals ; Hyperalgesia/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Hypothermia/metabolism* ; Neuralgia ; Brachial Plexus/injuries* ; Edema/metabolism*

To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.
Mice ; Animals ; Male ; Ischemic Stroke ; Recovery of Function/physiology* ; Insulin-Like Growth Factor I/pharmacology* ; Mice, Inbred C57BL ; TOR Serine-Threonine Kinases/metabolism* ; Stroke/drug therapy* ; Brain Ischemia/drug therapy* ; Mammals/metabolism*

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.
Humans ; Animals ; Mice ; Male ; Mutation, Missense ; Retrospective Studies ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Infertility, Male/genetics* ; Mutation ; Vas Deferens/abnormalities* ; Spermatogenesis/genetics*

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.
Humans ; Male ; Female ; Middle Aged ; Hemangiosarcoma ; Ki-67 Antigen ; Retrospective Studies ; Biomarkers, Tumor/metabolism* ; Prognosis ; Liver Neoplasms/pathology*

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

Objective: To describe the actual efficacy of programmed death-1 (PD-1)/ programmed-death ligand 1 (PD-L1) inhibitors in patients with metastatic non-small cell lung cancer (NSCLC) and explore potential prognostic predictive biomarkers. Methods: Patients with metastatic NSCLC who were treated with PD-1/PD-L1 inhibitors at Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to December 2019, either as monotherapy or in combination with other agents, were consecutively enrolled into this study. We retrospectively collected the data of demographics, clinical information and pathologic assessment to evaluate the therapeutic efficacy and conduct the survival analysis. Major endpoint of our study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Results: The ORR of 174 patients who underwent PD-1/PD-L1 inhibitor was 28.7%, and the DCR was 79.3%. Immune-related adverse events (irAEs) occurred in 23 patients (13.2%). Brain metastasis, line of treatment, and treatment patterns were associated with the ORR of metastatic NSCLC patients who underwent immunotherapy (P<0.05). After a median follow-up duration of 18.8 months, the median PFS was 10.5 months (ranged from 1.5 to 40.8 months) while the median OS was not reached. The 2-year survival rate was estimated to be 63.0%. The pathologic type was related with the PFS of metastatic NSCLC patients who underwent immunotherapy (P=0.028). Sex, age, brain metastasis and autoimmune diseases were associated with OS (P<0.05). Analysis of the receptor characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) predicting ORR of immunotherapy in metastatic NSCLC showed that the areas under the curve of NLR before immunotherapy (NLR(C0)), NLR after one cycle of immunotherapy (NLR(C1)) and ΔNLR were 0.600, 0.706 and 0.628, respectively. Multivariate logistic regression analysis showed that NLR(C1) was an independent factor of the ORR of metastatic NSCLC patients who underwent immunotherapy (OR=0.161, 95% CI: 0.062-0.422), and the efficacy of combination therapy was better than that of single agent (OR=0.395, 95% CI: 0.174-0.896). The immunotherapy efficacy in patients without brain metastasis was better than those with metastasis (OR=0.291, 95% CI: 0.095-0.887). Multivariate Cox regression analysis showed that NLR(C1) was an independent influencing factor of PFS of metastatic NSCLC patients after immunotherapy (HR=0.480, 95% CI: 0.303-0.759). Sex (HR=0.399, 95% CI: 0.161-0.991, P=0.048), age (HR=0.356, 95% CI: 0.170-0.745, P=0.006) were independent influencing factors of OS of metastatic NSCLC patients after immunotherapy. Conclusions: PD-1/PD-L1 inhibitors are proved to be efficacious and have tolerable toxicities for patients with metastatic NSCLC. Patients at advanced age could still benefit from immunotherapy. Brain metastasis is related to compromised response. Earlier application of immunotherapy in combination with other modalities enhances the efficacy without elevating risk of irAEs. NLR(C1) is an early predictor of clinical outcome. The OS of patients younger than 75 years may be improved when treated with immunotherapy.
B7-H1 Antigen/metabolism* ; Brain Neoplasms/drug therapy* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/pathology* ; Prognosis ; Programmed Cell Death 1 Receptor ; Retrospective Studies

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ² test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.
Blood Loss, Surgical ; Carcinoma, Hepatocellular/surgery* ; Female ; Hemorrhage ; Hepatectomy/methods* ; Humans ; Hypertension, Portal/surgery* ; Liver Failure ; Liver Neoplasms/surgery* ; Male ; Retrospective Studies ; Treatment Outcome

ObjectiveTo observe the clinical efficacy of Jiawei Xiaochaihutang combined with microwave ablation （MWA） in the treatment of primary hepatocellular carcinoma （HCC） and its influence on tumor microenvironment. MethodA total of 128 patients were randomly divided into control group （64 cases： 2 cases of dropout，2 cases of elimination，and 60 cases of completion） and observation group （64 cases： 3 cases of dropout，2 cases of elimination，and 59 cases of completion）. Both groups were given comprehensive treatment after MWA surgery. Patients in control group took Biejiajian Wan orally （3 g/time，3 times/d）， and those in observation group took Jiawei Xiaochaihutang （1 dose/d）. The treatment lasted for 3 consecutive months. The size of solid tumor before and after treatment was evaluated to record the progression-free survival （PFS）. The alpha-fetoprotein-L13 （AFP-L3），des-γ-carboxy prothrombin （DCP），Golgi protein 73 （GP73），tumor necrosis factor-α （TNF-α），transforming growth factor-β （TGF-β），vascular endothelial growth factor （VEGF） and matrix metalloproteinase-2 （MMP-2） levels，as well as performance status （PS），liver function and syndrome of liver depression and Qi stagnation scores were also detected before and after treatment. In addition， the incidence of side effects of grade Ⅲ and above was compared. ResultThe total effective rate of solid tumor in observation group was 91.53% （54/59），higher than that （76.67%， 46/60） in control group（χ²=4.895，P<0.05）. The PFS in observation group was （7.16±0.95） months， longer than that （6.24±0.89 months） in control group （P<0.01）. The effective rate of traditional Chinese medicine （TCM） syndrome in observation and control groups were 88.14% （52/59）and 70.00% （42/60）， respectively （χ²=5.897，P<0.05）. The observation group （57.63%，34/59） had higher marked effective rate of TCM syndrome than control group （31.67%，19/60） （χ²=8.116，P<0.01）. The AFP-13，DCP，GP73，TNF-α，TGF-β，VEGF and MMP-2 levels and the PS，liver function and syndrome of liver depression and Qi stagnation scores in observation group were lower than those in control group （both P<0.01）. The cumulative incidence of side effects of grade Ⅲ and above in observation and control groups was 16.95% and 33.33%， respectively（χ²=4.261，P<0.05）. ConclusionConsolidation treatment of HCC after MWA surgery with Jiawei Xiaochaihutang relieved symptoms and side effects，improved PS and liver function，regulated tumor microenvironment，inhibited tumor markers and prolonged survival time. The clinical effect was better than that of Biejia decoction pill， and thus it was worthy of clinical use.

PURPOSE: COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis. METHODS: In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively. RESULTS: A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO CONCLUSION Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients' hospitalstay.
COVID-19 ; Carbapenems ; Hospital Mortality ; Humans ; Intensive Care Units ; Klebsiella ; Prognosis ; Retrospective Studies ; SARS-CoV-2 ; Sepsis