Precancerous lesions of gastric cancer （PLGC） are a group of pathological changes caused by abnormalities in the structure， morphology， and differentiation of gastric mucosal epithelial cells. Since the early symptoms are hidden and non-specific， PLGC is not easy to be diagnosed and it has often developed into intermediate or advanced gastric cancer once being diagnosed and missed the best time for treatment. Accordingly， the incidence of this disease is increasing year by year， which lifts a heavy burden on the patients. The pathogenesis of PLGC is complex， involving inflammatory microenvironment， bile reflux， glycolysis， autophagy， and apoptosis. Currently， PLGC is mainly treated with anti-inflammatory and endoscopic therapies， which are difficult to curb the development of PLGC. Therefore， seeking a safe and effective therapy is an important topic of modern research. Traditional Chinese medicine （TCM）， characterized by treatment based on syndrome differentiation and a holistic view， exerts effects via multiple pathways， mechanisms， and targets. Recent studies have confirmed that TCM can regulate the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）， Wnt/β-catenin， Sonic Hedgehog， nuclear factor-κB （NF-κB）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， hypoxia-inducible factor-1α （HIF-1α）， neurogenic locus notch homolog protein （Notch）， nuclear factor E₂-related factor 2 （Nrf2） and other signaling pathways. By targeting these pathways， TCM can inhibit aerobic glycolysis， reduce oxidative stress， repair the inflammatory microenvironment， regulate cellular autophagy， and promote vascular normalization， thereby delaying or reversing PLGC. However， few researchers have systematically summarized the TCM regulation of PLGC-associated pathways. By reviewing the relevant articles at home and abroad， this paper summarized the roles of the above signaling pathways in the development of PLGC and the research progress in the regulation of signaling pathways by TCM in the treatment of PLGC， with a view to providing a new theoretical basis for the clinical research on PLGC and the drug development for this disease.

Gastric cancer （GC） is one of the most common cancers in the world， with hidden symptoms， complex pathogenesis， high morbidity， high mortality， and poor prognosis. As one of the classical apoptosis pathways， mitochondrial apoptosis has been widely described in the apoptosis escape by GC cells. Mitochondrial apoptosis can regulate the proliferation， invasion， and metastasis of GC cells via oxidative stress， cell cycle， mitochondrial membrane potential， mitochondrial translocation and other mechanisms， and it is one of the potential targets of traditional Chinese medicine （TCM） intervention to restore the mitochondrial function in GC. The theory of spleen-mitochondria in correlation explains that spleen deficiency and cancer toxin are the root causes of mitochondrial apoptosis. Accordingly， the TCM treatment should follow the basic principle of invigorating spleen to restore healthy Qi and removing cancer toxin to eliminate the root cause. Mitochondrial apoptosis can be promoted by inhibiting oxidative stress， promoting cell cycle arrest， and reducing mitochondrial membrane potential. This therapy can improve the energy metabolism， restore the mitochondrial structure and function， and prevent the occurrence and development of GC， with mild side effects and low drug resistance. However， the mechanism of mitochondrial apoptosis in GC and the target of TCM intervention in GC have not been systematically reviewed. Therefore， this paper systematically summarized the effects of mitochondrial apoptosis on the occurrence and development of GC and the role of TCM in the treatment of GC by intervening in mitochondrial apoptosis， aiming to provide a theoretical reference for the treatment and further research of GC.

Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.
Mice ; Animals ; Humans ; Hepatitis, Autoimmune/pathology* ; Signal Transduction ; Disease Models, Animal ; Stem Cells

Osteofacial compartment syndrome (OCS) is one of the serious complications in traumatic orthopedics. If not treated in time, OCS may result in irreversible damage to nerve and muscle,even amputation or death in serious condition. 5P presents to be the classic clinical diagnosis of OCS, but it is highly subjective and cannot timely and accurately judge the progression of the disease. Intracompartment pressure manometry is the main auxiliary method for the diagnosis of OCS. Although there are many manometry methods, there is still no authoritative pressure threshold as the diagnosis standard. Clinicians often aggressively perform fasciotomy to avoid serious complications, leading to unnecessary fasciotomy. The authors retrospectively reviewed the data of patients with OCS treated at Air Force Hospital of Eastern Theater of PLA from March 2010 to March 2020 and found that some patients with OCS had gradual alleviation of clinical symptoms after appropriate conservative treatments such as brace releasing, limb stabilization and swelling subsidence, with no need of fasciotomy. However, the symptoms of some patients progressively aggravated after the above-mentioned traditional treatments and timely fasciotomy was required. The authors graded the severity of OCS and proposed for the first time the OCS grading criteria according to quantitative clinical results and quantitative indicators such as ratio of mean blood flow velocity of bilateral arteries and pulse wave changes, aiming to take corresponding intervention measures for patients with different OCS classifications, carry out more precise treatment and avoid unnecessary fasciotomy.

Objective:To explore the efficacy of distracting external fixator for tibiofibular fractures combined with osteofascial compartment syndrome.Methods:A retrospective case-control study was conducted to analyze the clinical data of 62 patients with tibiofibular fractures combined with osteofascial compartment syndrome admitted to Air Force Hospital from Eastern Theater of PLA from March 2009 to March 2019, including 47 males and 15 females, aged 20-78 years［（47.1±13.4）years］. There were 30 patients with tibia shaft fractures, 17 with tibia plateau fractures and 15 with tibia distal fractures. The fractures were classified as type 4A in 18 patients, type 4B in 24 and type 4C in 20 according to AO/OT classification. Distracting external fixation was performed for 30 patients（Group A）and calcaneal tuberosity traction for 32 patients（Group B）. Levels of alanine aminotransferase（ALT）, urea nitrogen（BUN）, creatine kinase（CK）and lactate dehydrogenase（LDH）of the injured limb were compared between the two groups during traction. Additionally, the fasciotomy rate, time of damage control treatment（observation interval from trauma to stage II definitive surgery）, time of stage II definitive surgery, internal fixation modalities of stage II definitive surgery, rate of needle tract infection and rate of non-planned secondary surgery were compared between the two groups. The limb function was assessed using Johner-Wruhs scoring system at the last follow-up.Results:All patients were followed up for 12-22 months［（15.1±2.7）months］. Level of CK in Group A was 315.6（140.0, 531.5）U/L, significantly lower than that in Group B［465.5（277.0, 1240.5）U/L］（ P<0.05）. The two groups revealed no statistical differences in levels of BUN, CK and LDH（ P>0.05）. The fasciotomy rate in Group A［40%（12/30）］was higher than that in Group B［34%（11/32）］, but the difference was statistically insignificant（ P>0.05）. The time of stage II definitive surgery in Group A was（68.5±17.1）minutes, significantly lower than that in Group B［（89.0±15.1）minutes］（ P<0.05）. The rate of non-planned secondary surgery in Group A［3%（1/30）］was lower than that in Group B［25%（8/32）］（ P<0.05）. There were no statistically significant differences in time of damage control treatment, internal fixation modalities of stage II definitive surgery and rate of needle infection between the two groups（ P>0.05）. According to Johner-Wruhs scoring system, the function in Group A were excellent in 17 patients, good in 5, fair in 2 and poor in 6 at the last follow-up, with the excellent rate of 73%. However, the difference was not statistically significant when compared to Group B: excellent in 13 patients, good in 3, fair in 7 and poor in 9, with the excellent rate of 50%（ P>0.05）. Conclusion:Compared with calcaneal tuberosity traction, the distracting external fixation of tibiofibular fractures combined with osteofascial compartment syndrome can attenuate soft tissue damage during the traction and shorten the time of stage II definitive surgery by maintaining intraoperative fracture reduction.

Objective To explore the surgical indications for pancreas-kidney surgery and summarize the experiences of ,selecting surgical approaches ,formulating immunosuppressive regimens and preventing complications .Methods A total of 145 donor simultaneous pancreas-kidney transplants in uremic patients with T1DM/T2DM between 2002 and 2018 were retrospectively analyzed .Based upon surgical approaches and immunosuppressive agents ,they were divided into three eras of 2002-2010 ,2011-2014 and 2015-2018 respectively .Patient profiles ,survival outcomes of patient and graft , surgical techniques ,immunosuppressive agents and incidence of common complications were compared among different groups .Results The overall 1/3/5-year patient and graft survival rates of three groups were above 75％ and the survival rates of group Ⅰ were inferior to those of groups Ⅱ and Ⅲ(P<0 .001) .The overall 1/3/5-year pancreas graft survival rates were the highest in group Ⅲ and the lowest in group Ⅱ (P=0 .004) .In the 2015-2018 group ,ipsilateral pancreas-kidney transplantation and SE-ED surgery were more preferred .Regarding the incidence of complications ,graft thrombosis frequently occurred from 2011 to 2014 and intestinal obstruction was more common from 2002 to 2010 .For univariable analysis of graft loss ,anticoagulation programme with argatroban monohydrate were 0 .28 times likely to lose pancreas graft (OR= 0 .28 ,95％ CI:0 .09-0 .86) and T1DM patients were 4 times likely to have kidney graft loss (OR=4 .08 ,95％ CI:1 .37-12 .15) .Conclusions SPK is an effective treatment for uremic diabetics . Effective perioperative management and preventing complications are crucial for prolonging patient and graft survivals .

Objective To summarize the clinical characteristics of recipients of renal transplantation who used tacrolimus extended-release capsules,to optimize the postoperative immunosuppressive regimen,and provide reference for the therapeutic administration of imnmunosuppressive agents after renal transplantation.Methods 156 patients who had renal transplant in our center were divided into three groups according to the time of the change of the extended-release tacrolimus capsules,and the blood glucose and blood lipids of each group were analyzed.Results The longer the postoperative duration was,the higher proportion of new-onset diabetes cases (P =0.025).There was no significant difference among the three groups of immune induction regimens.The immnunosuppressive regimen was changed from MMF (68.8％ in G3 group) to MPA (72％ in G1 group).With the prolongation of postoperative time,the dosage of tacrolimus decreased gradually.The mean tacrolimus concentration in the 3 groups was significantly different (P＜0.001) as time went by.There was no significant change in the average daily dosage before and after the change.The trough value before and after the change in the first two groups was significantly different (P＜0.001).Conclusion The extended-release tacrolimus capsules could be used in different stages after renal transplantation.After the conversion of the extended-release tacrolimus capsules,the dosage of adjuvant is reduced,and blood concentration and creatinine level are more stablem which is a more optimized immunosuppressive regimen.

Objective To search for application ways for the safe and effective clinical methods of arsenic-containing Compound Qinghuang Powder (Compound QHP) for the treatment of myelodysplastic syndrome (MDS). Methods Totally 200 patients with MDS were included in the study and treated with Compound QHP. After one-month treatment, the 60 patients with the blood arsenic concentrations <20 μg/L were randomly divided into control group and treatment group, with 30 cases in each group. Control group was given stable treatment, while the treatment group was given increased dose of realgar; blood arsenic concentration was detected monthly; realgar 0.1 g was increased each time until blood arsenic concentrations ≥20 μg/L and realgar ≤0.3 g/d. The blood arsenic concentration, clinical efficacy and safety in the two groups were observed. Results Totally 24 cases in each group were included for evaluation finally. The average blood arsenic concentration of treatment group was significantly higher than those of control group (P<0.05). The rate of hematologic improvement was significantly higher in treatment group (54.2％, 13/24) than that in control group (29.2％, 7/24) , with significant difference (P<0.05). The Hb, ANC, and PLT significantly increased in treatment group after treatment (P<0.05). There was no significant difference of incidence rate of adverse reaction observed between treatment group and control group (P>0.05). Conclusion In application of Compound QHP, the blood arsenic concentration can be monitored to adjust the daily dose of realgar, thus to increase the effective blood arsenic concentration, and then improving efficacy without increasing the clinical toxicity.

Objective To analyze the clinical efficacy and safety of compound Qinghuang powder (compound QHP) for treatment of myelodysplastic syndromes (MDS) and its association with blood arsenic concentration (BAC). Methods 40 patients with MDS were treated with compound QHP, and the clinical efficacy, safety, and its association with BAC were evaluated after treatment for 6, 9 months, respectively. Results After treatment for 6 months, the rate of hematology improvement was 32.5 % (13/40), and the effective rate was 87.5%(35/40). 21 cases depended on the blood transfusion before treatment, after treatment 6 cases completely got rid of blood transfusion and the blood transfusion of another 6 cases was decreased by more than 50 %. The absolute neutrophil count was increased from (0.50±0.13)×109/L to (0.93±0.33)×109/L (t= 4.130, P= 0.0008). The hemoglobin content was increased from (71.06±14.82) g/L to (80.41±27.35) g/L (t= 2.233, P= 0.0321). After treatment for 9 months, 76.2 % (16/40) of the patients got rid of blood transfusion or blood transfusion reduction was more than 50%. The platelet count was increased from (45.04 ± 24.38)×109/L to (60.65±29.46)×109/L (t= 2.241, P= 0.0335). The incidence of abdominal pain and diarrhea after treatment for 1, 3 and 6 months were 12.5 % (5/40), 10.0 % (4/40) and 5.0 % (2/40), respectively, all belonging to mild level . Before treatment , there were 12 patients with abnormal liver function , including 6 cases back to normal after treatment, and 6 cases of significantly relieved, without new case with abnormal liver function. Before treatment, there were 10 cases with abnormal myocardial enzymes, including 1 cases back to normal after treatment and 9 cases significantly relieved, without new case with abnormal myocardial enzymes. No patient with abnormal renal function was observed before and after treatment. The BAC was (7.71±5.65) μg/L before treatment, which was significantly lower than that of 1, 3 and 6 months [(29.27±9.07)μg/L, (27.79 ±10.18) μg/L and (31.98 ±12.55) μg/L respectively, all P< 0.0001]. There was no significant change of BAC among the patients after treatment for 1, 3 and 6 months (P> 0.05). The BAC in efficacy group [(33.48 ±12.56) μg/L] was significantly higher than that in non-efficacy group [(21.46 ±6.00) μg/L] (t=2.089, P=0.035). 12.5% (5/40) of the patients had mild gastrointestinal side effects after treatment for 1 month, while the BAC of them [(16.93 ±1.80) μg/L] was significantly lower than that in patients without gastrointestinal side effects [(31.78±1.39 ) μg/L, P<0.0001]. The occurrence rate of abdominal pain and diarrhea was decreased after treatment for 3 and 6 months, while the BAC was increased gradually. Conclusions Compound QHP is effective in the treatment of MDS with mild adverse reactions. There is no damage to the heart, liver, and renal function. Besides, it shows that reducing the gastrointestinal adverse reactions and maintaining the effective concentration of BAC play a significant role in the effect of compound QHP in the treatment of MDS.

Objective To analyze the blood arsenic concentration and the safety of compound Qinghuang powder(compound QHP)in patients with myelodysplastic syndrome(MDS).Methods A total of 45 MDS patients received treatment with compound QHP (the treatment group, n=45). The concentration of blood arsenic in different time was determined by atomic fluorescence spectrometry. The clinical safety of compound QHP was evaluated by analyzing the symptoms of adverse reaction and organ function. The comparison were MDS patients with Qinghuang powder (QHP group, n=47) and healthy people. Results There was no significant difference of the blood arsenic concentration between the treatment group and the healthy control group (P=0.450),while after the treatment for 1 month those concentrations significantly increased (P=0.000). There were no significant difference between the blood arsenic concentration after treatment for 1, 3, and 6 months (P=0.240). The incidence of adverse reaction in the treatment group was significantly lower than that in QHP group(χ2=4.720, P=0.030). The incidence of adverse reactions in the digestive tract was significantly lower in the treatment group than that in QHP group (χ2=4.650, P=0.034). The blood arsenic concentration of patients with abdominal pain diarrhea was significantly lower than those without abdominal pain diarrhea (P=0.020). Before treatment in the compound QHP group, there were 21 cases with increased myocardial enzymes, 10 cases with abnormal liver function and 4 cases with renal dysfunction, respectively. After treatment at 6th month, these indicators returned to normal with 7 cases of myocardial enzymes, 6 cases of liver function and 1 case of renal function, respectively. There was no new case with abnormal myocardial enzymes, liver function and renal dysfunction, respectively. Conclusions Arsenic could be absorbed in the digestive tract into blood in MDS patients after treatment with arsenic-containing compound QHP, and the blood arsenic concentration remained stable during the course of treatment. The adverse reactions were mainly mild gastrointestinal symptoms, but no heart, liver or renal function damage was observed. The incidence of abdominal pain diarrhea in patients treated with compound QHP was significantly lower than that with QHP.