[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma].

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.

This phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/d [20 mg/d in patients aged ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cutoff, 13 (11.9%) of 109 and 15 (27.3%) of 55 patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy end point) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859; P = .008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade 3 or higher infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as #NCT01084252.

[The prognostic relationship between CD56 expression and newly diagnosed multiple myeloma].

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Hypomethylation of CTCFL promoters as a noninvasive biomarker in plasma from patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third deadliest cancer in the world with high morbidity and poor prognosis. CTCFL (CCCTC-binding factor like) is a member of the cancer testis antigen (CTA) family with oncogenic properties. To demonstrate whether the hypomethylation of CTCFL promoters in plasma could be used as a noninvasive biomarker to predict poor prognosis of HCC, we extracted cell-free DNA from the plasma and detected the methylation status of CTCFL in 43 HCC, 5 liver cirrhosis and 6 benign lesion samples using methylation specific PCR (MSP). Our study indicated that the hypomethylation of CTCFL promoters in HCC plasma samples (60.4%) was significantly different from that in benign lesion plasma samples (16.7%) with a p-value of 0.043. Analysis of clinicopathological data showed that the methylation status of CTCFL promoters was significantly correlated with microvascular involvement (MVI) (p=0.001) and postoperative recurrence (p=0.031). Furthermore, clinical prognosis data of 347 HCC patients from The Cancer Genome Atlas (TCGA) database displayed that the hypomethylated group had worse overall survival than the hypermethylated group (p=0.0056). In conclusion, we provide evidence that the hypomethylation of CTCFL promoters in cell-free DNA is a biomarker for monitoring HCC patients, which can be used as a noninvasive prediction index for tumor recurrence and provide the individualized decision-making for clinicians.

[The investigation and prognosis in patients with non-alcoholic fatty liver disease and coronary vulnerable plaque].

Objective: To investigate the prevalence and prognosis of non-alcoholic fatty liver disease (NAFLD) complicated with coronary vulnerable plaque (VP). Method: Consecutive patients were included who had undergone coronary artery CT angiography (CCTA) from January 1, 2011 to January 30, 2015 at the First People's Hospital of Neijiang. NAFLD was diagnosed according to the liver imaging findings (liver/spleen CT ratio≤1.0) and clinical data. Baseline data, diagnosis, vulnerable plaque were recorded and followed up. The end points included all-cause death rate, cardiac death rate, non-fatal myocardial infarction rate, and elective coronary revascularization rate. Result: A total of 1 069 patients were eventually recruited in this study, including 316 (29.6%) cases diagnosed as NAFLD. In patients with NAFLD, 130 (41.1%) cases had vulnerable plaque, which was significantly higher than 217 of 753 non-NAFLD patients (28.8%) (P<0.01). The percentages of spotty calcification, low attenuation plaque, positive remodeling and napkin ring sign in NAFLD cohort were 36.5%, 14.2%, 17.6% and 6.8% respectively, while those corresponding in non-NAFLD cohort were 18.4%, 6.3%, 5.8% and 3.2% respectively. The proportion of each vulnerable feature in NAFLD cohort was significantly higher than that in the non-NAFLD cohort, with P values of 0.016, 0.028, 0.019 and 0.042, respectively. The cardiac mortality rate in NAFLD group was significantly higher than and that of non-NAFLD group (7.0% vs. 3.6%, P=0.044). Multivariate Cox analysis suggested that NAFLD was not an independent risk factor for cardiac death. NAFLD subgroup (n=316) was divided into VP positive group (NAFLD+VP+, n=130) and VP negative group (NAFLD+VP-, n=186). The mean follow-up time was 4.6±1.3 years. All-cause mortality rate, cardiac death rate, elective coronary artery reconstruction rate, non-fatal myocardial infarction rate in NAFLD+VP+group were 20.8%, 12.3%, 25.4%, 13.8% respectively, which were significantly higher than those corresponding rates in NAFLD+VP-group (5.9%, 3.2%, 8.6%, 6.5%) (P<0.01, 0.002,<0.01, and 0.032 respectively). Conclusion: The incidences of cardiac mortality, elective coronary revascularization, and non-fatal myocardial infarction are significantly higher in patients with NAFLD than those without. NAFLD combined with vulnerable plaque of coronary arteries predicts worse prognosis.

Vitamin D-supplemented yogurt drink reduces Candida infections in a paediatric intensive care unit: a randomised, placebo-controlled clinical trial.

BACKGROUND: The prevalence of Candida infections in paediatric intensive care units (PICUs) has dramatically increased as a result of resistance to conventional anti-fungal treatments. Because vitamin D has been shown to exhibit fungicidal activity against Candida infection in an in vitro antimicrobial screening, we aimed to investigate the effect of vitamin D on Candida infections in the PICU. METHODS: Four hundred sixteen eligible children aged between 12 months to 5 years old admitted to the PICU, who were on broad-spectrum antibiotic therapy, participated in the study. Patients were randomly assigned to two study groups, receiving a plain yogurt drink (placebo group) or supplemented with 300 IU day-1 vitamin D (VD group). Primary outcome was defined as the incidences of Candida colonisation (Candida isolated from rectal swab) 14 days after enrollment. Secondary outcome measures were Candida growth in blood (candidaemia) and urine (candiduria). RESULTS: The prevalence of candiduria as well as candidaemia was significantly lower in the VD-treated group (26 cases) than in the placebo group (62 cases). The mean (SD) length of PICU stay was obviously lowered in the VD group [11.8 (1.2) days] compared to the placebo group [15.2 (2.3 days)], whereas cases of patient death were similar between the two groups. CONCLUSIONS: Supplementation of vitamin D effectively reduces infections of Candida in children who were critically ill and on broad-spectrum antibiotic treatment.

Curcumin converts Foxp3+ regulatory T cells to T helper 1 cells in patients with lung cancer.

The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The mechanism by which curcumin regulated the Tregs was observed by cell culture approaches. The results showed that the frequency of peripheral Treg was markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for 2 weeks. The peripheral Th1 cells were increased in LC patients after the curcumin therapy. The data of the in vitro experiments showed that curcumin converted the LC patient-isolated Tregs to Th1 cells via repressing the gene transcription of forkhead protein-3 and increasing the expression of interferon-γ. In conclusion, curcumin can convert LC patient-isolated Tregs to Th1 cells. The results suggest that curcumin may improve the antitumor immunity by regulating the tumor specific immune tolerance.

[The clinic experience of implantable diaphragm pacer in a patient with high cervical spinal cord injury and literature review].

Objective: To report the use of implantable diaphragm pacer (IDP) in a patient with high cervical spinal cord injury(HCSCI). Methods: A 14-year-old male patient, who suffered from a HCSCI at C2 neurological level and had been on a ventilator for 2 years, received IDP in August 2017 at China Rehabilitation Research Center. A systematic literature review was performed on IDP in patients with HCSCI in Pubmed, CNKI, and Wanfang databases, using the keywords: phrenic nerve and electrical stimulation and spinal cord injury; IDP and spinal cord injury; breathing pacemaker system and spinal cord injury. All fields were covered from 1970/01/01 to 2018/01/01 in Pubmed, from 1981/01/01 to 2018/01/01 in CNKI, and from 1900/01/01to 2018/01/01 in Wanfang. Results: No spontaneous breathing was observed preoperatively in the patient. The electrical response of phrenic nerves was intact on the right, but unresponsive on the left. We got started with the IDP at 4 weeks after surgery. The threshold voltage of the right hemidiaphragm pacing was 0.1 V and at the level of 0.7 V with an optimal effect. No significant diaphragmatic contraction was found at left side with the extent up till 0.7 V. The maximum tidal volume was 840 ml when electrical stimulation was given at an intensity of 0.7 V bilaterally. The bilateral stimulation voltage at 0.1-0.2 V, pacing frequencies at 9 beats/min in bed, or at 12 beats/min on wheelchair, were set to maintain the tidal volume at the level of (435±32) ml. After 2-week adaptive training, the patient could wean from the ventilator for 12 hours and had a normal blood gas analysis. At 6 week after surgery, with the aid of IDP, the patient could get out in wheelchair for outdoor activities. By literature review, we found 78 English papers, including 6 clinical trials, 10 reviews, and 11 Chinese papers, consisting of 8 reviews, 1 study in animal, and 2 news reports. Extensive contents, such as preoperative evaluation, preoperative preparation, surgical procedures, complications, surgical outcomes, and animal model studies of IDP were involved. The indications of IDP reported by literature were: (1) central alveolar hypoventilation; (2) Sleep apnea syndrome (Biot's respiration); (3) Respiratory failure induced by brainstem injury or disease; (4) Respiratory failure induced by spinal cord injury or disease above C3 level. Conclusion: Our case study confirmed the therapeutic effect of IDP on patients with respiratory failure caused by HCSCI.

Characterization of Prohibitins in Male Reproductive System and their Expression under Oxidative Stress.

PURPOSE: We investigated the expression and location of prohibitin 1 and 2 of the prohibitin family in the male reproductive system and their potential roles during the oxidative stress response in a rat model. MATERIALS AND METHODS: Semiquantitative polymerase chain reaction, Western blot, immunohistochemistry and indirect immunofluorescence were performed to examine the expression and localization of prohibitins. Oxidative damage was evaluated using a commercially available malondialdehyde kit. Histological damage induced by doxorubicin injection was examined by hematoxylin and eosin staining. RESULTS: Prohibitin 1 and 2 were ubiquitously expressed in various human tissues with distinct high expression in the epididymis. In the human testis and epididymis they were localized in the cytoplasm of diverse cell types. Prohibitin 1 was located on the entire tail region of human ejaculated spermatozoa while prohibitin 2 was specifically localized on the equatorial region. In spermatozoa from young men with asthenozoospermia the percent of spermatozoa with positive staining as well as the fluorescence intensity of prohibitin 2 was much lower than in the spermatozoa of healthy donors. Uniform expression of prohibitins in the testis and epididymis of the rat during postnatal development suggested conserved and vital biological functions. Moreover under oxidative stress induced by doxorubicin injection the expression of prohibitin 1 and 2 was significantly down-regulated in the rat testis with significant histomorphological changes. CONCLUSIONS: To our knowledge this research represents the first systematic study of prohibitins in the male reproductive system. It lays the foundation for further functional studies and provides potential therapeutic targets for infertility induced by oxidative stress.

OAB epidemiological survey of general gynaecology outpatients and its effects on patient quality of life.

AIMS: To survey the prevalence rate of overactive bladder (OAB) among general gynaecology outpatients, it's connection to common benign gynaecological diseases and its effects on patient quality of life (QOL). METHOD: A questionnaire survey on urination and its effects on QOL was administered to 2500 general gynaecology outpatients aged ≥18 who visited our hospital which is in Peking between October and November 2012. Additionally, their menstrual history and diseases were documented, according to their medical records. RESULTS: In total, 2161 effective questionnaires (86.4%) were collected from the respondents, who were aged 18-97 years. The overall OAB prevalence rate was 8.8% (191/2161), and the OAB prevalence rate in women >50 years was significantly higher (X(2) = 7.656, P < 0.05). Moreover, the OAB prevalence rate (25.8%) among patients suffering from pelvic organ prolapse was significantly higher than the rate (8.6%) among patients without pelvic organ prolapse (X(2) = 11.238, P < 0.05). Multi-factor logistic regression indicated that age (OR = 1.504, 95% CI = 1.072-2.111) and pelvic organ prolapse (OR = 2.512, 95% CI = 1.109-5.688) were risk factors for OAB among the respondents. Additionally, with the rise of OAB severity, its effects on the QOL of OAB patients, like urinary urgency, nocturia, frequency and urge incontinence increased accordingly. CONCLUSIONS: The OAB prevalence rate among general gynaecology outpatients was 8.8%, and the effects of OAB on QOL increased with the worsening of the disease.

Phase I dose-escalation study of cabazitaxel administered in combination with gemcitabine in patients with metastatic or unresectable advanced solid malignancies.

Taxane-gemcitabine combinations have demonstrated antitumor activity. This phase I study (NCT01001221) aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus gemcitabine and to assess the preliminary efficacy of this combination. The patients included had metastatic or unresectable solid tumors and had exhausted standard treatment. Cohorts of three to six patients received cabazitaxel (15-20 mg/m) before (part 1a) or after (part 1b) gemcitabine (700-1000 mg/m) on Day 1 and gemcitabine alone on Day 8. Prophylactic growth factors were not allowed in cycle 1. In part 1a (n=12), five patients received 20 mg/m cabazitaxel plus 1000 mg/m gemcitabine (20/1000), five received 15/900, two received 15/700. In part 1b, all six patients received the lowest dose (700/15). At all doses, two or more patients experienced a DLT, regardless of administration sequence, including febrile neutropenia (n=4), grade 4 neutropenia (n=2), grade 4 thrombocytopenia (n=2), and grade 3 aspartate transaminase increase (n=1). The MTD was not established as all cohorts exceeded the MTD by definition. All patients experienced an adverse event; the most frequent all-grade nonhematologic events were fatigue (66.7%), decreased appetite (50.0%), and diarrhea (44.4%). The most frequent grade 3-4 hematologic abnormalities were neutropenia (83.3%), leukopenia (77.8%), and lymphopenia (72.2%). Toxicity was sequence-independent but appeared worse with gemcitabine followed by cabazitaxel. Durable partial responses were observed in three patients (prostate cancer, appendiceal cancer, and melanoma). The unacceptable DLTs with cabazitaxel plus gemcitabine, at doses reduced more than 25% from single-agent doses, preclude further investigation.

Enhanced LPS-induced peritonitis in mice deficiency of cullin 4B in macrophages.

Cullin 4B (CUL4B), a member of the cullin protein family, is a scaffold protein of the CUL4B-RING-E3 ligase complex that ubiquitinates intracellular proteins.CUL4B's targets include cell cycle-regulated proteins and DNA replication-related molecules. In this study, we generated myeloid-specific Cul4b-deficient mice (Cul4b(f/y);LysM-Cre(KI/KI)) to investigate the influence of Cul4b deficiency on innate immunity, especially on the function of macrophages. Our results show that an intraperitoneal injection of lipopolysaccharide (LPS) led to a significant decrease in body weights and increased leukocyte infiltrates with increased chemokines in the peritoneal cavity of Cul4b(f/y);LysM-Cre(KI/KI) mice. However, the proinflammatory cytokines, IL-6 and TNF-α did not increase in LPS-injected Cul4b(f/y);LysM-Cre(KI/KI) mice. Furthermore, bone marrow-derived macrophages from Cul4b(f/y);LysM-Cre(KI/KI) mice secreted higher levels of chemokines but lower levels of TNF-α and IL-6 upon LPS stimulation. Of note, increased proliferation of Cul4b-deficient macrophages was also observed. These results show that myeloid-specific Cul4b deficiency worsens LPS-induced peritonitis. In addition, Cul4b deficiency leads to enhanced DNA replication and proliferation, increased production of chemokines but a decreased production of proinflammatory cytokines of macrophages. Our data highlight a new role of cullin family, CUL4B, in the immune system.

Effect of nourishing and purging fire Chinese herbal mixture on delaying light-induced premature puberty in rats.

OBJECTIVE: To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture (NYPF) in delaying light-induced premature puberty in rats. METHODS: Twenty-one days old female Sprague-Dawley rats were randomly assigned to normal group (N), long light exposure group (L), NYPF and normal saline group (NS). Rats in the L, NYPF and NS groups were exposed to 16 h: 350 lux light/8 h: dark, while rats in the N group were exposed to 12 h: 50 lux light/12 h: dark. NYPF and normal saline was administered to the rats in the NYPF group or NS group, respectively, from day 21. Five rats in every group were sacrificed at 9 p.m. on day 28 (P28), on the day when rat's vulva opened in the L group (L-VO), on the day when the first estrous interphase occurred in rats of L group (L-E1), and on the day when the second estrous interphase occurred in rats of L group (L-E2), respectively. RESULITS: On day 34, all rats in the L group, 80% of rats in the NS group, 40% of rats in the N group, and 20% of rats in the NYPF group showed complete opening of the vulva. At P28, mRNA level of hypothalamic kisspeptin (Kiss-1) in the L group was significantly higher than that in the N group (P < 0.05). The rats in the L and NS groups had significantly lower hypothalamic arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3) mRNA levels than those in the N group (P < 0.05), whereas RFRP-3 mRNA level was significantly higher in the NYPF group than that in the L group (P < 0.05). At L-VO, the ovarian index of the L and NS groups was significantly higher than that of the N group (P < 0.05) and estradiol (E2) level of the NYPF group was significantly lower than that of the N and NS groups (P < 0.05); hypothalamic Kiss-1 mRNA level in the L and NS groups was significantly higher than that in the N and NYPF groups (P < 0.05), whereas hypothalamic RFRP-3 mRNA level in the L, NYPF, and NS groups was significantly lower than that in the N group (P < 0.05). At L-E1, E2 level of the L and NS groups was significantly higher than that of the N group (P < 0.01), whereas it was significantly lower in the NYPF group than that of the N, L, and NS groups (P < 0.01), and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group (P < 0.05); levels of serum melatonin and ovarian melatonin receptor 1 (MT-1) mRNA in the L, NYPF, and NS groups were significantly lower than those in the N group (P < 0.05). At L-E2, the uterine organ index of the NYPF group was significantly lower than that of the L group (P < 0.05); and ovarian MT-1 mRNA level of the L and NS groups was significantly lower than that in the N group (P < 0.05). CONCLUSIONS: NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration, and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.

[Discussion on surgical treatment mode of diabetic foot wounds].

Diabetic foot wounds have a high incidence and uneven therapeutic effect, so it is necessary to explore the suitable treatment mode of diabetic foot wounds. The existing surgical treatment modes for diabetic foot wounds include the multi-disciplinary team (MDT) cooperation mode and the "five-in-one comprehensive limb salvage" treatment mode. These two modes have their own advantages, but are inconvenient to some extent. In response to this problem, the author's team proposed the wound surgical integrated treatment (WSIT) mode based on years of experience in repairing diabetic foot wounds, emphasizing the perioperative management by MDT, and the local wound management by WSIT team, which significantly improved the diagnosis and treatment efficiency of patients with diabetic foot wounds.

[Research advances on the application of free flaps in repairing diabetic foot ulcers].

Free flaps have been successfully used in the repair of diabetic foot ulcers (DFUs), which can reduce amputation rate, maintain normal gait of patients, and improve life quality of patients. However, there are still many challenges in the repair of DFUs with free flaps, and many problems need to be solved. This paper summarizes the selection of patients, preoperative cautions, types of flaps, methods of vascular anastomosis, clinical effects, and existing problems in using free skin flaps for repairing DFUs.

Case report: Spontaneous remission of metastatic endometrial carcinoma through the Lim Lifestyle.

This case report records 2 discrete episodes of spontaneous remission of metastatic endometrial cancer (into peritoneum and omentum) in a 41-yr-old female following the "Lim Lifestyle" therapy alone. This lifestyle is an originally formulated holistic approach toward cancer consisting of nutritional, spiritual, and mental therapies. Cancer regression was measured symptomatologically, serologically, and radiologically (resolved ascites and reduced omental cake).

Sex difference in the expression of PD-1 of non-small cell lung cancer.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

Electron transport chain-dependent and -independent mechanisms of mitochondrial H2O2 emission during long-chain fatty acid oxidation.

Oxidative stress in skeletal muscle is a hallmark of various pathophysiologic states that also feature increased reliance on long-chain fatty acid (LCFA) substrate, such as insulin resistance and exercise. However, little is known about the mechanistic basis of the LCFA-induced reactive oxygen species (ROS) burden in intact mitochondria, and elucidation of this mechanistic basis was the goal of this study. Specific aims were to determine the extent to which LCFA catabolism is associated with ROS production and to gain mechanistic insights into the associated ROS production. Because intermediates and by-products of LCFA catabolism may interfere with antioxidant mechanisms, we predicted that ROS formation during LCFA catabolism reflects a complex process involving multiple sites of ROS production as well as modified mitochondrial function. Thus, we utilized several complementary approaches to probe the underlying mechanism(s). Using skeletal muscle mitochondria, our findings indicate that even a low supply of LCFA is associated with ROS formation in excess of that generated by NADH-linked substrates. Moreover, ROS production was evident across the physiologic range of membrane potential and was relatively insensitive to membrane potential changes. Determinations of topology and membrane potential as well as use of inhibitors revealed complex III and the electron transfer flavoprotein (ETF) and ETF-oxidoreductase, as likely sites of ROS production. Finally, ROS production was sensitive to matrix levels of LCFA catabolic intermediates, indicating that mitochondrial export of LCFA catabolic intermediates can play a role in determining ROS levels.

Identification of a novel HLA-A allele, A*11:60, in a Taiwanese family.

We report the identification and sequence analysis of a new HLA-A11* variant, A*11:60 allele, found in a Taiwanese leukaemic patient and his siblings. The novel A*11 variant is identical to A*11:03 in exon 2 but differs from A*11:03 in exon 3 by one nucleotide substitution at position 527 (A→T) causing an amino acid change at codon 152 E (Glu)→V (Val) (GAG→GTG). In comparison with HLA-A*11:01:01, allele A*11:60 has two nucleotide differences in exon 3: at nt 524 (A→G) (CAT→CGT) and at nt 527 (C→T) (GCG→GTG) leading to two amino acid variations at residues 151 H (His)→R (Arg) and 152 A (Ala)→V (Val).

Discovery of two novel HLA-B alleles, B*46:13:03 and B*15:189, in two Taiwanese volunteer bone marrow donors by sequence-based typing.

We report here two novel HLA-B alleles, B*46:13:03 and B*15:189, discovered in two Taiwanese volunteer bone marrow donors. The sequence of B*15:189 has a nucleotide sequence possibly derived from a recombination event between HLA-B*39:01:01 and B*15:01:01:01, while the origin of the sequence B*46:13:03 was less obvious to postulate, considering the low frequency of B*46:13 in the general population and the silent mutations involved. Our report here adds further HLA polymorphism to the growing lists of HLA-B*46 and HLA-B*15 and provides an additional HLA information for donor search programme for patients undergoing transplant.