Tumor Therapy: Targeted Substances Metabolism Reprogramming Induces Tumor Ferroptosis / 生物化学与生物物理进展

There are huge differences between tumor cells and normal cells in material metabolism, and tumor cells mainly show increased anabolism, decreased catabolism, and imbalance in substance metabolism. These differences provide the necessary material basis for the growth and reproduction of tumor cells, and also provide important targets for the treatment of tumors. Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells, resulting in excessive accumulation of lipid peroxide, causing damage to lipid membrane structure and loss of function, and ultimately cell death. The regulation of ferroptosis involves a variety of metabolic pathways, including glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism and iron metabolism. In order for tumor cells to grow rapidly, their metabolic needs are more vigorous than those of normal cells. Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs. Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway, enhanced glutamine metabolism, increased nucleic acid synthesis, and iron metabolism tends to retain more intracellular iron. Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system. The state of high oxidative stress makes tumor cells more susceptible to redox imbalances, causing intracellular lipid peroxidation, which ultimately leads to ferroptosis. Therefore, in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment. Ferroptosis, as a regulated form of cell death, can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells, which has great potential value in tumor treatment. This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.

The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis / 生物化学与生物物理进展

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

Research advances of adipose stem cell matrix gel in promoting wound healing / 中华烧伤杂志

In recent years, with the problem of aging population in China being prominant, the number of patients with chronic wounds such as diabetic foot, pressure ulcer, and vascular ulcer is increasing. Those diseases seriously affect the life quality of patients and increase the economy and care burden of the patients' family, which have been one of the most urgent clinical problems. Many researches have confirmed that adipose stem cells can effectively promote wound healing, while exogenous protease is needed, and there are ethical and many other problems, which limit the clinical application of adipose stem cells. Adipose stem cell matrix gel is a gel-like mixture of biologically active extracellular matrix and stromal vascular fragment obtained from adipose tissue by the principle of fluid whirlpool and flocculation precipitation. It contains rich adipose stem cells, hematopoietic stem cells, endothelial progenitor cells, and macrophages, etc. The preparation method of adipose stem cell matrix gel is simple and the preparation time is short, which is convenient for clinical application. Many studies at home and abroad showed that adipose stem cell matrix gel can effectively promote wound healing by regulating inflammatory reaction, promoting microvascular reconstruction and collagen synthesis. Therefore, this paper summarized the preparation of adipose stem cell matrix gel, the mechanism and problems of the matrix gel in promoting wound repair, in order to provide new methods and ideas for the treatment of chronic refractory wounds in clinic.

Research advances of photosensitizer in photodynamic therapy of glioblastoma / 药学学报

Glioblastoma is a malignant tumor in central nervous system, which has strong invasion, poor prognosis and short survival time. At present, the main treatment strategy of glioblastoma is surgical excision, supplemented by radiotherapy and chemotherapy. However, due to incomplete resection and high recurrence rate, it is urgent to find novel therapeutic method for glioblastoma. Photodynamic therapy, as a promising non-surgical treatment, provides a new strategy for postoperative adjuvant therapy of glioblastoma. This review summarizes the mechanism and clinical application of photodynamic therapy mediated by various photosensitizers in glioblastoma, in order to provide help for the treatment of glioblastoma.

Effects of colloid preload on the incidence of hypotension in spinal anesthesia for cesarean section: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Hypotension is a common complication caused by spinal anesthesia (SA), which may have adverse impacts on the condition of the parturient and fetus. Liquid infusion was found to be relatively effective for reducing the incidence of hypotension. However, the question of whether colloid preload can optimize hemodynamic variables in the cesarean section remains controversial. This study aims to determine the effects of colloid preload on the incidence of hypotension induced by SA in elective cesarean section.@*METHODS@#Related keywords were searched on PubMed, EMBASE, and Cochrane Library from inception dates to May 2020. Studies included were evaluated for eligibility and quality. The primary outcome was the intra-operative incidence of hypotension and severe hypotension. The secondary outcomes included the lowest intra-operative systolic blood pressure, the maximal intra-operative heart rate, the intra-operative needs of ephedrine and phenylephrine, the incidence of maternal nausea and/or vomiting, and neonatal outcomes (umbilical artery pH and Apgar scores). Apart from the above, RevMan 5.3 was used for the data analysis.@*RESULTS@#Altogether nine randomized controlled trials were included in the meta-analysis. There were no significant differences in the incidence of intra-operative hypotension, severe hypotension, or neonatal outcomes between the colloid preload group and control group, except for the umbilical artery pH.@*CONCLUSION@#This meta-analysis suggests that colloid preload does not significantly reduce the incidence of hypotension associated with SA in elective cesarean section.

Neuromuscular Pharmacodynamics of Rocuronium in Diabetic Rats / 中国医学科学院学报

Objective To investigate diabetes-mediated changes in the neuromuscular pharmacodynamics of rocuronium in rats. Methods Diabetes mellitus was induced by a single injection of streptozotocin in rats.A total of 24 male SD rats were assigned to four groups using random number table:the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group(6 rats per group).The sciatic nerve was stimulated in a rain-of-four(TOF)pattern,and the twitch tension changes in the tibialis anterior muscle were demonstrated by mechanomyography after intravenous injection of rocuronium in vivo.The time course characteristics of rocuronium,including onset time,and the recovery time from rocuronium injection to TOF ratio 75%(RT75%)and 90%(RT90%),were recorded,and half maximal inhibitory concentration(IC)values of rocuronium were determined using a four-parameter dose response curve. Results Compared with the normal controls,the diabetic rats had significantly prolonged onset time of rocuronium,while the RT75% and RT90% were decreased at all rocuronium doses(PConclusion Diabetes is associated with the rat skeletal muscle hyposensitivity to rocuronium,which is featured by prolonged onset time of rocuronium,decreased RT 75% and RT 90%,and right shift of the cumulative dose-response curve of rocuronium.

Clinical Application and Development of Near-infrared Spectroscopy for Monitoring Regional Cerebral Oxygen Saturation / 中国医学科学院学报

The near-infrared spectroscopy has been applied to the continuous and noninvasive monitoring of regional cerebral oxygen saturation,providing information about the equilibrium between cerebral oxygen supply and consumption. This article reviews the mechanism,clinical application,and limitations of this technique.

Common molecular etiology of patients with nonsyndromic hearing loss in Tibetan, Tu nationality, and Mongolian patients in the northwest of China.

CONCLUSION: In the northwest of China, the prevalence of mutations of the three prominent deafness-related genes, GJB2, SLC26A4, and mitochondrial DNA (mtDNA) 12S rRNA, among Tibetan, Tu nationality, and Mongolian subjects is high, at 19%, 28.57%, and 21.05%, respectively. Molecular genetic screening for these mutations and genetic counseling are effective methods to prevent the occurrence of hereditary hearing loss. OBJECTIVE: To analyze the prevalence of the three common deafness genes GJB2, mtDNA, and SLC26A4 gene mutations in Tibetan, Tu nationality, and Mongolian patients with nonsyndromic hearing impairment in the Northwest region of China. METHODS: Genomic DNA was extracted from a total of 189 Tibetan, Tu nationality, and Mongolian probands from the northwest of China. PCR and direct sequencing were used to analyze the coding region of GJB2, mtDNA, and SLC26A4 genes. RESULTS: The mutant allele rate of GJB2 gene was 6.2% in Tibetan and 11.22% in Tu nationality patients, c.235delC was the most prevalent mutation, accounting for 75% of the mutant GJB2 alleles. Mutant allele frequency of SLC26A4 in Tibetan, Tu nationality, and Mongolian subjects was 4.54%, 6.12%, and 15.79% respectively; p.IVS7-2A>G was the most common form. Mongolian cases were significantly higher than Tibetan cases (χ² = 7.281, p = 0.007 and p < 0.05). mtDNA A1555G mutation was detected in six Tibetan, five Tu nationality, and one Mongolian subject; one Tibetan patient carried the C1494T mutation.

Association of nutrition with treatment compliance and toxicities in patients undergoing chemoradiation after gastrectomy / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association of nutritional status with treatment compliance and toxicities in patients undergoing chemoradiation therapy (CRT) after gastrectomy.</p><p><b>METHODS</b>From September 2010 to May 2012, 40 patients with gastric cancer received adjuvant CRT in the Department of Radiation, Shanghai Cancer Center. Data including clinical data, weight loss of perioperative period, dynamic changes of weight, NRS 2002 score, PG-SGA score, lymph cell count and serum albumin during CRT, toxic effects and nutritional interventions were collected. Treatment compliance of CRT and adjuvant chemotherapy was recorded. Associations among nutrition, toxicities and treatment compliance were statistically studied.</p><p><b>RESULTS</b>Weight loss percentage from pre-operation to pre-CRT(T1-T2) was 10.0%, which was significantly higher than that of 4.3% during CRT(T3) (P<0.05). Adverse reaction incidence of digestive tract during T3 was 95.0% (38/40). Patients with weight loss >5% during T3 had higher ratio of >II degree digestive tract adverse reaction [91.3% (21/23) vs. 76.5% (13/17), P<0.01] and higher ratio of >3 symptoms of digestive tract[82.4% (14/17) vs. 39.1% (9/23), P<0.05] as compared to those with weight loss ≤5% during T3. Fourteen patients (35.0%) did not complete the synchronous CRT. Factors related to incompletion of CRT were weight loss >7% after surgery (T1) or >10% during T1-T2, malnourishment before CRT, dependence on nutritional support during CRT. Factors related to incompletion of adjuvant chemotherapy were weight loss >5% during CRT(T3), requirement for nutritional support and NRS 2002 score ≥5 at the end of radiation (all P<0.05).</p><p><b>CONCLUSIONS</b>Nutritional deterioration before CRT may aggravate the toxicities and reduce compliance of CRT in patients with radical resection of gastric cancer. Malnutrition during CRT may impair compliance to adjuvant chemotherapy. Therefore, early and persistent nutritional interventions are crucial considerations of strategies of multidisciplinary treatment for patients with gastric cancer.</p>

Comparison of Cookgas and Fastrach intubating laryngeal mask airway with fiberoptic bronchoscope in anticipated difficult airway management / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare the clinical effectiveness of fiberoptic bronchoscope (FOB)-guided intubation through the Cookgas intubating laryngeal airway(CILA)and the Fastrach intubating laryngeal mask airway (FT-LMA) in the management of anticipated difficult airways.</p><p><b>METHODS</b>Sixty patients with all three difficult intubation criterion (thyromental distance<60 mm, interincisor distance<35 mm, and Mallampati class 3 or 4) undergoing elective plastic surgery under general anesthesia were randomly allocated into CILA group (n=30) and FT-LMA group (n=30). After anesthesia being induced and CILA or FT-LMA being inserted, the patients were treated with FOB-guided intubation through CILA or FT-LMA. The success of the intubating laryngeal airway(ILA)insertion and FOB-guided intubation, the number of attempts, and the duration of the successful attempt were recorded.</p><p><b>RESULTS</b>The ILA was inserted successfully in 30 patients from CILA group and 27 patients from FT-LMA group. Three failed cases in FT-LMA group were inserted successfully with CILA. In CILA group, the first FOB-guided intubation attempt succeeded in 26 patients, and 4 cases were intubated at the second attempt. In 27 patients of FT-LMA group, 20 cases were intubated successfully at the first attempt, 4 cases at the second attempt, and 3 cases failed; of these three failed patients, two patients were intubated smoothly with FOB through CILA at the first attempt, one was intubated by FOB via CILA at the second attempt. The duration of FT-LMA insertion [(35.3±12.8)s] was significantly longer when compared with CILA [(23.9±17.5)s] (P<0.05). However, the duration of FOB-guided intubation through CILA and FT-LMA [(48.6±13.5)s vs.(53.2±14.2)s] and the time of ILA removal [(40.4±10.2)s vs. (38.5±11.3)s] were not significantly different between these two groups (P>0.05). The adverse events during and after intubtion were not significantly different between these two groups.</p><p><b>CONCLUSIONS</b>FOB-guided intubation through CILA and FT-LMA is safe and feasible for the management of anticipated difficult airways. However, in patients with severe scar contracture of face and neck and those with huge expander in neck, the CILA insertion and FOB-guided intubation via CILA is superior to FT-LMA.</p>

Analysis of the hereditary etiology of 336 patients with non-syndromic sensorineural hearing loss from Ningxia Hui Autonomous Region of China / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the molecular genetic causes and their characteristics of deafness in Ningxia province, we established screening of three common hereditary deafness genes in 336 deaf and hard-of-hearing patients in this district.</p><p><b>METHODS</b>Peripheral blood samples were obtained from a total of 336 patients with non-syndromic sensorineural hearing loss in parts of special education schools in Ningxia province to extract genomic DNA. The mitochondrial DNA 12S rRNA m.1555A > G mutation was screened by PCR Alw26I digestion and sequence analysis PCR and direct sequencing were used to analyze the coding region of GJB2 and exons 8 and 19 of SLC26A4. Statistical analysis was performed by using SPSS 11.0 software. Frequencies of different GJB2 or SLC26A4 mutations were compared between Han and Hui people.</p><p><b>RESULTS</b>Among these 336 patients, seven cases (2.08%, 7/336) were found to carry mtDNA 12S rRNA m.1555A > G homozygous mutation, 45 cases (13.39%) were caused by GJB2 mutations and 28 cases (8.33%) had two mutated alleles (homozygote and compound heterozygote) of SLC26A4. In detail, 16.67% (56/336) patients carried GJB2 mutations including 11 single mutant carriers. The allele frequency of c.235delC and c.299_300delAT were 9.52% (64/672) and 2.68% (18/672), respectively, making up 81.19% (82/101) of all pathogenic mutated alleles for GJB2. The single mutant allele carriers of SLC26A4 is 32, and two types (c.919-2A > G and c.2168A > G) accounted for 95.29% (24/27) mutations, totally. We also found that statistically significant differences in c.919-2A > G and c.2168A > G frequencies between Han and Hui people (c.919-2A > G, χ(2) = 8.229, P = 0.004; c.2168A > G, χ(2) = 5.277, P = 0.022). However, there was no statistically significant difference in GJB2 mutation between Han and Hui people.</p><p><b>CONCLUSIONS</b>GJB2 mutation was a primary cause for non-syndromic sensorineural hearing loss in Ningxia province, and c.235delC was the most common mutant forms of GJB2. c.919-2A > G and c.2168A > G were common mutant forms of SLC26A4, their frequencies were also statistically significant differences between Han and Hui people.</p>

Application of conscious sedation with midazolam, propofol and sufentanil for patients in plastic surgery / 中华整形外科杂志

<p><b>OBJECTIVE</b>To observe the effectiveness of conscious sedation with midazolam, propofol and sufentanil for patients in plastic surgery.</p><p><b>METHODS</b>81 patients, scheduled for plastic surgery, were randomly selected to receive conscious sedation with midazolam 0.05 mg x kg(-1) and sufentanil 0.1 microg x kg(-1) intravenously, following by a continuous infusion of midazolam-propofol-sufentanil combination (midazolam 5 mg + propofol 200 mg + sufentanil 10 microg, a total of 23 ml). The initial infusion rate was 0.2 ml x kg(-1) x h(-1), and was adjusted (in 20% of initial infusion rate increment) to maintain OAA/S score as 11 during the operation. The patients' vital signs, discomfort and level of sedation were evaluated at 5 to 10 min intervals until the end of the surgery. The complications (i. e. anoxemia, apnea, restlessness, nausea and vomiting), anesthesia duration and drug consumption were recorded. The drug infusion was discontinued at 5 - 10 min before the end of the surgical procedure. On the first postoperative day, patients were asked to rate their satisfaction with the anesthetic management and whether they would choose to receive the same anesthetic technique if necessary in the future.</p><p><b>RESULTS</b>The OAA/S score decreased from 20.0 +/- 0 to 11.9 +/- 2.6 after midazolam and sufentanil IV (P < 0.05), and was maintained as 10.5-11.1 during the procedure. At the end of the procedure, the OAA/S score returned to 16.0 +/- 2.2, which was also lower significantly compared with baseline value (P < 0.05). The induction of sedation produced a significant decrease in SBP and DBP (P < 0.05) and no significant changes in heart rate (P > 0.05). At the end of the procedure, SBP, DBP and HR returned to the baseline value. The anoxemia happened in 11 cases, apnea in 5 cases and restlessness in 2. No nausea and vomiting occurred. The anesthesia duration and consumption of midazolam, propofol and sufentanil were (101.1 +/- 42.5) min, (8.4 +/- 3.7) mg, (189.1 +/- 88.7) mg and (18.2 +/- 5.6) microg respectively. In an interview on the first postoperative day, 96% (78/ 81) of the patients were satisfied with their anesthesia and were willing to receive the same anesthetic technique if necessary in the future.</p><p><b>CONCLUSION</b>Conscious sedation with midazolam, propofol and sufentanil is an effective anesthetic technique for patients in plastic surgery.</p>

Mitochondrial DNA A1555G mutation analysis in 802 nonsyndromic hearing impairment patients / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of the mitochondrial DNA (mtDNA) A1555G mutation in nonsyndromic hearing impairment (NSHI) patients from Gansu province.</p><p><b>METHODS</b>Subjects included 802 students selected from five Deaf-Mute Schools in Gansu. DNA was extracted from peripheral blood of all patients. The mitochondrial DNA target fragments were amplified by polymerase chain reaction (PCR). The Mutations were detected by AIw26I digestion and sequence analysis.</p><p><b>RESULTS</b>The homoplasmic A1555G mutation was found in 67 individuals from 802 patients (8.4%). Fifteen of these 67 patients had family histories.</p><p><b>CONCLUSIONS</b>The mtDNA A1555G mutation had a higher incidence in Gansu population with nonsyndromic hearing impairment than other studies. The data not only gaven more evidences that the prevalence of mtDNA A1555G mutation in china was higher than that in Europe and America, but also gaven valuable information for gene diagnosis, genetic counseling and would improve the safety of aminoglycoside antibiotic therapy.</p>