OBJECTIVE: To explore clinical characteristics, lesion sites and correlation differences of different types of diabetic foot gangrene, and to provide evidence-based basis for clinical classification of diabetic foot gangrene. METHODS: A retrospective analysis was conducted on 266 patients with newly diagnosed diabetic foot gangrene who were admitted from January 2018 to December 2018, including 183 males and 83 females, aged from 35 to 92 years old with an average of (69.55±10.84) years old, and they were divided into wet gangrene group and dry gangrene group according to the different natures of gangrene. There were 139 patients in wet gangrene group, including 98 males and 41 females, aged from 35 to 90 years old with an average of (68.95±10.93) years old. There were 127 patients in dry gangrene group, including 85 males and 42 females, aged from 38 to 92 years old with an average of (70.21±10.75) years old. Body mass index (BMI), waist-to-hip ratio (WHR), body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, and Wagner grade between two groups were recorded to evaluate symptoms and signs. The white blood cell count (WBC), neutrophil percentage (NEUT%), and C-reactive protein (C-reactive protein), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) in peripheral blood between two groups were detected and compared to evaluate the infection status;the severity of diabetic peripheral neuropathy (DPN) was evaluated by using Toronto Clinical Scoring System (TCSS);the degree of pain in patients with diabetic foot gangrene was evaluated by numerical rating scale (NRS); ankle-brachial index (ABI) and popliteal artery blood flow velocity were used to evaluate the degree of arterial lesions. Spearman correlation analysis was used to analyze the correlations between gangrene TCSS, ABI and age, BMI, WHR, body temperature, calf skin temperature difference, WBC, NEUT%, CRP, ESR, PCT, IL-6, NRS, and Wagner classification indicators. RESULTS: The body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, Wagner grade, WBC, NEUT%, CRP, ESR, PCT, IL-6, TCSS score, ABI, and popliteal artery blood flow velocity in wet gangrene group were higher than those in dry gangrene group (P<0.01), and BMI, WHR, and NRS score in dry gangrene group were higher than those in wet gangrene group;the differences were all statistically significant (P<0.01). The results of Spearman correlation analysis showed TCSS score of gangrene patients was correlated with body temperature (r=0.214), calf skin temperature difference (r=0.364), WBC (r=0.240), NEUT% (r=0.291), CRP (r=0.347), ESR (r=0.167), PCT (r=0.241), IL-6 (r=0.316), and popliteal fossa arterial blood flow velocity (r=0.261) and Wagner grade (r=0.273) were positively correlated, and the differences were statistically significant (P<0.01). ABI was negatively correlated with age (r=-0.183), BMI (r=-0.252), WHR (r=-0.288), and NRS score (r=-0.354), and the differences were statistically significant (P<0.01). CONCLUSION Diabetic foot gangrene is an extremely difficult and critical disease. Wet gangrene has a significant synergic effect with infection and neuropathy, while dry gangrene is closely related to vascular occlusion. The main contradiction of gangrene could be revealed through blood vessels, nerves and infection, providing evidence-based basis for the selection of debridement timing, anti-infection strategies and revascularization, with the aim of reducing the risk of amputation.
Humans ; Male ; Female ; Aged ; Middle Aged ; Diabetic Foot/diagnosis* ; Aged, 80 and over ; Adult ; Retrospective Studies ; Gangrene/physiopathology* ; C-Reactive Protein

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.

Idiosyncratic adverse drug reactions (IDR) induce severe medical complications or even death in patients. Alert structure in drugs can be metabolized as reactive metabolite (RM) in the bodies, which is one of the major factors to induce IDR. Structure modification and avoidance of alert structure in the drug candidates is an efficient method for reducing toxicity risks in drug design. This review briefly summarized the recent development of the methodologies for structure optimization strategy to reduce the toxicity risks of drug candidates. These methods include blocking metabolic site, altering metabolic pathway, reducing activity, bioisosterism, and prodrug.
Binding Sites ; Cytochrome P-450 Enzyme System ; metabolism ; Drug Design ; Drug Discovery ; methods ; Drug Recalls ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Humans ; Structure-Activity Relationship

The methyl group plays an important role in the rational drug design. Introducing methyl into small molecules has become an important strategy of lead compound optimization. The application of methyl in drug design is reviewed in this paper. Methyl can modulate the physicochemical, pharmacodynamic, and pharmacokinetic properties by ortho effect, inductive effect, and conformational effect. It also improves the metabolic stability as a soft metabolic point. In addition, introducing methyl into drug molecules can also be applied as a strategy in new uses of old drugs and generate me-too drugs.
Drug Design ; Hydrophobic and Hydrophilic Interactions ; Lipid Metabolism ; Methylation ; Pharmaceutical Preparations ; chemical synthesis ; chemistry ; metabolism ; Solubility ; Stereoisomerism ; Structure-Activity Relationship

OBJECTIVETo study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP).

METHODSelf-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP.

RESULTThe contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05).

CONCLUSIONThere were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.

Adolescent ; Biomarkers ; blood ; metabolism ; Bronchoalveolar Lavage Fluid ; chemistry ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lung ; metabolism ; pathology ; Male ; Mucin-1 ; blood ; metabolism ; Pneumonia, Mycoplasma ; blood ; metabolism ; Pulmonary Surfactant-Associated Protein A ; blood ; metabolism ; Pulmonary Surfactant-Associated Protein D ; blood ; metabolism ; Severity of Illness Index

OBJECTIVETo screen and identify zebrafish mutants with erythropoiesis defects by N-ethyl-N-nitrosourea (ENU) mutagenesis and large-scale forward genetic screening using beta e 1 as the marker.

METHODSThe chemical mutagen ENU was used to treat healthy wild-type male fish (AB strain, F0). The surviving ENU-treated fish were mated with wild-type female fish to generate F1, and further F2 family was generated by F1 family intercross. The adult F2 fish were intercrossed within each F2 family and the resulting F3 embryos from each crossing were subjected to whole mount in situ hybridization (WISH) with the beta e 1 probe. Mutagenesis was performed by treating the male zebrafish with ENU to induce mutations in pre-meiotic germ cells to generate the founders, which were outcrossed to obtained the F1 fish. The F1 fish from different founders were mated to generate the F2 families. F3 embryos from the sibling cross in the F2 family were examined by whole mount in situ hybridization using beta e 1-globin probe. The putative mutants were then characterized with different hematopoiesis markers.

RESULTS AND CONCLUSIONWe identified 4 beta e 1-deficient mutants with erythropoiesis defects, including two with specific erythiod lineage defects and two with concurrent lymphopoiesis defects.

Animals ; Erythropoiesis ; genetics ; Ethylnitrosourea ; Female ; Gene Expression Regulation, Developmental ; Male ; Mutagenesis, Insertional ; Mutation ; Zebrafish ; genetics

Objective To investigate the effects and safety of sequential treatments with methotrexate and mifepristone for ectopic pregnancy with fetal cardiac activity.Methods 4 cases of ectopic pregnancy with fetal car- diac activity in our hospital were given by sequential therapy with methotrexate and mifepristone.Serum?-HCG,liv- er function and renal function,blood routine and gastrointestinal response were observed.Results 4 cases of ectopic pregnancy with fetal cardiac activity with 1～4 periods of sequential treatments were cured.Except light gastroin- testinal response,and one had slight rise of serum ALT level and AST level,no one had rnyelosuppression and heavy hepatic injury.Conclusion The sequential therapy with methotrexate and mifepristone is an effective and safe method for the treatment to ectopic pregnancy with fetal cardiac activity.