Objective To explore the effects of human umbilical cord mesenchymal stem cells (HUC?MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms. Methods Podocytes were divided into six groups according to treatment: ⑴ normal glucose group (NG);⑵high glucose group (HG);⑶mannitol control group (NG+Ma);⑷HUC?MSC co?culture group (HUC?MSCs); ⑸ recombinant human hepatocyte growth factor treatment group (rhHGF);⑹ neutralizing antibody group(HGF?NtAb). Cytometry and Hoechst staining were used to detect the apoptosis rates. Western blot was used to measure the ratio of active PARP to total PARP and the level of Bcl?2. Immunofluorescence was used to study podocytic apoptosis and injury. Neutralizing antibody (NtAb) was used to block its function and the recombinant cytokine was added to induce its function. Results High glucose induced podocytic apoptosis in a time?dependent manner, HUC?MSCs co?culture decreased the podocytic apoptosis rate and the expression of PARP (all P﹤0.05), increased the expression of Bcl?2, prevented the reduced expression and maintained the normal arrangement of podocytic podoplanin. The rhHGF prevented podocytic apoptosis and injury similarly to HUC?MSCs, the beneficial effect of HUC?MSC decreased when blockade of HGF. Conclusions HUC?MSCs co?culture ameliorates podocytic apoptosis and injure induced by HG, probably through secreting soluble HGF.

OBJECTIVE: To explore the effects of Salvia miltiorrhiza on renal morphology and renal function of rats with streptozotocin diabetes. METHODS: Thirty male Wistar rats were randomly divided into three groups, which were normal control group, untreated group and Salvia miltiorrhiza-treated group. Diabetic nephropathy was induced in rats of the last two groups by intraperitoneal injection of streptozotocin after unilateral nephrectomy. Then the rats in the normal control and untreated groups were fed with normal saline while those in the Salvia miltiorrhiza-treated group were fed Salvia miltiorrhiza preparation for 8 weeks. The glomerular volume (VG), kidney-to-body weight ratio (KW/BW), urinary albumin excretion rate (UAER) and creatinine clearance (Ccr) were observed. The expression levels of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF), fibronectin (FN) and plasminogen activator inhibitor-1 (PAI-1) were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) at the end of the experiment. RESULTS: UAER, Ccr, VG and KW/BW ratio were significantly higher in the untreated group than those in the normal control group (P<0.05). The expression levels of TGF-beta1, CTGF, PAI-1 and FN in the untreated group were also significantly higher as compared with those in the normal control group (P<0.05). UAER, Ccr, VG, KW/BW ratio and the levels of TGF-beta1, CTGF, PAI-1 and FN in the Salvia miltiorrhiza-treated group were obviously lower than those in the untreated group (P<0.05). CONCLUSION: Salvia miltiorrhiza can protect rats with streptozotocin diabetes from diabetic nephropathy by suppressing the over-expressions of TGF-beta1, CTGF, PAI-1 and FN in renal cortex.

Objective:To analyze the clinical characteristics and neurophysiological features of patients with neuralgic amyotrophy (NA) and explore their neurological function status.Methods:Clinical data and neurophysiological findings of 90 patients diagnosed with NA at Beijing Tsinghua Changgung Hospital from September 2016 to January 2024 were collected and their clinical phenotypes and neurophysiological characteristics were systematically summarized and analyzed.Results:Among the 90 patients, males accounted for 60.0% (54 cases) and females accounted for 40.0% (36 cases). The duration of the disease was 12 (3, 36) months (ranged from 1 week to 5 years). The onset age of the patients was 58 (30, 70) (21-87) years. Unilateral involvement was noted in 94.4% (85/90) of patients, exhibiting a left-to-right ratio of 1∶1.3, while only 5.6% (5/90) had bilateral involvement. The majority of patients demonstrated a monophasic clinical course with a recurrence rate of just 2.2% (2/90). The primary clinical manifestations included upper limb pain in 70.0% (63/90) of patients, which progressed to muscle weakness and atrophy within 1 day to 1 month, whereas 30.0% (27/90) of patients without significant pain symptoms. Lesions predominantly affected the upper trunk of the brachial plexus, which accounted for 64.4% (58/90) of patients. Distal nerve injuries in the upper limb were observed in 14.4% (13/90) of patients, with 6.7% (6/90) demonstrating isolated anterior interosseous nerve involvement and another 6.7% (6/90) exhibiting isolated posterior interosseous nerve involvement; 1 case had concurrent anterior and posterior interosseous nerve damage. Additionally, 1 case presented with bilateral phrenic nerve involvement, and another patient had isolated posterior tibial nerve injury. Electrophysiological evaluations of patients with NA revealed that axonal damage to motor nerve fibers was a hallmark feature of the condition. Among patients undergoing motor nerve conduction studies, 68.8% (55/80) exhibited decreased compound muscle action potential amplitude, and 31.3% (25/80) had prolonged latency. Sensory nerve conduction was normal in 60.0% (48/80) of patients, while abnormalities included prolonged latency in 15.0% (12/80), reduced amplitude in 12.5% (10/80), slowed conduction velocity in 8.8% (7/80), and absent waveforms in 3.8% (3/80) of patients. The rates of abnormal nerve conduction findings in motor nerves were the highest in the suprascapular nerve (70.6%, 36/51), followed by the axillary nerve (58.3%, 35/60), musculocutaneous nerve (50.7%, 35/69), long thoracic nerve (6/17), and both anterior and posterior interosseous nerves (7.5%, 6/80 each). In sensory nerves, abnormalities were predominantly noted in the lateral antebrachial cutaneous nerve (30.0%, 12/40). Needle electromyography demonstrated neurogenic damage, most frequently affecting the infraspinatus muscle (69.2%, 18/26), biceps brachii (68.1%, 49/72), and deltoid muscle (65.3%, 47/72). The positive rate of magnetic resonance neurography (MRN) for NA was 62.1% (41/66), among which 63.4% (26/41) showed localized swelling of the brachial plexus, 51.2% (21/41) exhibited T 2 hyperintensity, and 4.9% (2/41) demonstrated denervated changes in the muscles. The positive rate of ultrasound for NA was 71.1% (59/83), with 91.5% (54/59) showing nerve swelling and 8.5% (5/59) exhibiting hourglass constriction .Conclusions:NA is a peripheral neuropathy characterized by spontaneous pain, limb weakness, and (or) muscle atrophy primarily. Its clinical phenotype predominantly involves damage to the upper trunk of the brachial plexus, which can also manifest as isolated mononeuropathy. Neurophysiological findings most commonly reveal the neurogenic damage to the muscles innervated by the upper trunk of the brachial plexus, mainly characterized by the axonal damage to the motor nerves, and pure motor nerve damage may also be observed. MRN and neuroultrasound can assist in qualitative diagnosis.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Objective:To investigate the effect of sodium octanoate on renal-intestinal ischemia- reperfusion injury (IRI) after resuscitation from traumatic cardiac arrest in pigs.Methods:Twenty-two miniature piglets with a body weight of (37.6±2.5)kg were divided into three groups according to the random-number table method: normal group ( n=7), IRI group ( n=7) and IRI-treated group ( n=8). A renal-intestinal IRI model of the pig was established by allowing femoral artery to bleed through blood pump at a rate of 2 ml·kg -1·min -1 until cardiac arrest, followed by whole blood transfusion through the femoral vein at a rate of 5 ml·kg -1·min -1 after observation for 6 minutes, and 50% of total blood loss was reinfused before resuscitation. Both the IRI group and IRI-treated group were with IRI model, while normal group was just monitored without induction of IRI. Besides, IRI-treated group was injected intravenously with sodium octanoate (30 mg/kg) for 1 hour at 5 minutes after restoration of spontaneous circulation (ROSC). (1) The rate of resuscitation success, survival rate at 4, 24 hours after resuscitation, blood loss when reaching cardiac arrest criteria and resuscitation time when reaching the ROSC criteria were compared in the three groups. (2) Levels of serum creatinine (SCr), urea nitrogen (BUN), intestinal fatty acid binding protein (iFABP) and diamine oxidase (DAO) were measured before resuscitation and at 1, 2, 4, 24 hours after resuscitation. (3) The animals were sacrificed at 24 hours post-resuscitation to harvest renal and intestinal tissues rapidly. TUNEL test was applied for the cellular apoptosis index. Prussian blue was used to detect the rate of iron deposition. Western blot analysis was used to measure levels of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member4 (ACSL4). Results:In three groups, all pigs survived. There was no significant difference in blood loss or resuscitation time between IRI group and IRI-treated group (all P>0.05). There was no significant difference in levels of SCr, BUN, iFABP or DAO before resuscitation and at 1, 2, 4, 24 hours after resuscitation in normal group (all P>0.05). But their levels were gradually increased at 1, 2, 4, 24 hours after resuscitation from that before resuscitation in IRI group and IRI-treated group (all P<0.01). Among three groups, levels of SCr, BUN, iFABP and DAO had no significant difference before resuscitation (all P>0.05), but showed obvious increase in IRI group and the IRI-treated group at 1, 2, 4, 24 hours after resuscitation compared with normal group, especially in IRI group (all P<0.01). In normal group, IRI group and IRI-treated group after 24 hours for resuscitation, the cellular apoptosis index of renal tissues was (2.3±0.8)%, (44.0±5.4)% and (13.8±4.3)%; the cellular apoptosis index of intestinal tissues was (2.6±0.9)%, (61.3±10.4)% and (20.8±3.7)%; the rate of iron deposition of renal tissues was (0.6±0.1)%, (3.9±1.0)% and (1.7±0.3)%; the rate of iron deposition of intestinal tissues was (0.8±0.1)%, (4.9±0.9)% and (2.1±0.5)% (all P<0.01). The cellular apoptosis index and rate of iron deposition of both renal and intestinal tissues were the highest in IRI group. The renal-intestinal expression of GPX4 in IRI group and IRI-treated group was lower than that in normal group at 24 hours after resuscitation (all P<0.05), with the lowest in IRI group. The renal-intestinal expression of ACSL4 in IRI group and IRI-treated group was higher than that in normal group at 24 hours after resuscitation (all P< 0.01), with the highest in IRI group. Conclusion:Sodium octanoate can reduce renal-intestinal IRI after resuscitation from traumatic cardiac arrest in pigs, the mechanism for which is probably due to that sodium octanoate can inhibit cellular apoptosis and reduce ferroptosis by regulating the expression levels of GPX4 and ACSL4.