Diabetic nephropathy(DN), a prevalent microvascular complication of diabetes, has emerged as a leading cause of end-stage renal disease worldwide. Recent studies on the dual-specific phosphatase (DUSP) family have revealed a significant reduction in DUSP expression levels in renal disease, suggesting that enhancing its expression may mitigate or alleviate the symptoms associated with renal disease. The primary function of DUSP is to mediate the dephosphorylation of mitogen-activated protein kinase (MAPK), which effectively inhibits the activation of the MAPK pathway, thus playing a crucial regulatory role in the onset and progression of DN. This article aims to investigate the correlation between DN and DUSP and to summarize the current research advancements concerning DUSP in the context of DN, providing new insights and essential theoretical foundations for its diagnosis and treatment.

Objective To explore the polymorphism of tyrosinase (TYR) and melanocortin 1 receptor (MC1R) genes and their mRNA expression levels in relation to coat-color phenotypes in guinea pigs, providing genetic markers for locating dominant traits in guinea pigs. Methods A total of 57 self-bred ordinary-level guinea pigs were selected and divided into three groups based on coat color: white (n=22), variegated (n=22) and black (n=13). The guinea pigs were euthanized with an overdose of pentobarbital sodium via intraperitoneal injection. DNA was then extracted from the dorsal skin tissue. Polymorphism in the coding sequence (CDS) of the exons of the TYR and MC1R genes in each group was detected by cloning and sequencing. The mRNA expression of the two genes in skin tissues was detected by real-time fluorescent quantitative PCR to investigate the relationship between these genes and guinea pig coat color. Results A single nucleotide polymorphism (SNP) site was found in the CDS region of TYR exon Ⅰ, where the base A was replaced by G. All white guinea pigs had the G/G genotype for TYR, while no deep-colored (variegated and black) guinea pigs exhibited the G/G genotype for TYR. Most deep-colored guinea pigs had the A/A genotype, and a few had A/G genotype. The A/A genotype frequency in black guinea pigs was higher than in variegated guinea pigs. A 2 760 bp sequence deletion was identified in the exon of the MC1R gene, marked as the - gene, with non-deleted samples marked as N gene. Most white guinea pigs had the -/- genotype for MC1R, variegated guinea pigs mainly had the -/N genotype, and black guinea pigs mainly had the N/N genotype, with a few showing the -/N. The TYR gene expression level was higher in white guinea pigs, lower in variegated guinea pigs, and intermediate in black guinea pigs, but there was no significant difference among the three groups (P>0.05). The MC1R gene expression level in white guinea pigs was extremely low, while both variegated and black guinea pigs showed significantly higher levels than white guinea pigs (P<0.01). Black guinea pigs showed significantly higher levels than variegated guinea pigs (P<0.05). ConclusionThe TYR and MC1R genes synergistically regulate coat color of guinea pigs. The G-site mutation in the TYR gene may lead to albinism, and the change of N-site in the MC1R gene affects the depth of the coat color.

ObjectiveThe utilization of assisted reproductive technology to rescue genetically modified mouse strains with reproductive disorders provides a reference for improving techniques to preserve valuable experimental mouse strains. MethodsIn vitro fertilization-embryo transfer (IVF-ET) technology was performed on 28 strains of infertile male mice aged 9-18 months. Several indicators such as sperm density and sperm motility in infertile male mice were assessed to select the most viable sperm for IVF-ET experiments. Fertility rate, abnormal egg rate, and birth rate were recorded after the birth of the pups. An optimized ovarian transplantation procedure was applied to 12 strains of infertile female mice aged 8-18 months. 6-week-old female mice with the same genetic background were selected as recipients. One intact ovary was removed from each recipient mouse, and the contralateral oviduct was ligated. An ovary from a donor mouse was isolated and transplanted orthotopically into the side where the ovary had been removed in the recipient mouse. Twenty-one days post-surgery, recipient mice were co-housed with 8-week-old wild type male mice of the same genetic background for breeding. Data such as the pregnancy rate and live birth rate of the recipients were recorded after the birth of the pups. ResultsIVF-ET successfully rescued 28 mouse strains, with the oldest male mice being 18 months old. The success rate of the first round of IVF-ET experiments was 89.29% (25/28). The average fertility rate of IVF in infertile male mice was (51.01±14.97)%, the abnormal egg rate was (9.03±5.28)%, and the birth rate of offspring mice was (18.60±7.03)%. 39 out of 40 ovarian transplant recipient mice survived, with a pregnancy rate of 33.33% (13/39) for ovarian transplant recipients, and a live birth rate of 17.95% (7/39). Four mouse strains were successfully rescued using optimized ovarian transplantation technology, with the oldest female mice being 18 months old. 8 strains were not rescued as they failed to produce offspring that survived to sexual maturity. ConclusionIVF-ET is an effective approach for rescuing mice with reproductive disorders caused by different reasons, especially for those beyond the optimal breeding age. Ovarian transplantation technology can also be used as an alternative for aged female mice. But its success rate is relatively lower than that of IVF-ET, and carries a higher experimental risk.

OBJECTIVE To systematically investigate the current status and effectiveness of the standardized on-the-job training program for community clinical pharmacists in Shanghai， and to provide a scientific basis for optimizing the training scheme. METHODS A questionnaire survey was conducted to collect the data from trainees and mentor pharmacists who participated in the program between 2016 and 2024. The survey examined their basic information， evaluations of the training scheme， satisfaction with training outcomes， and suggestions for improvement. Statistical analyses were also conducted. RESULTS A total of 420 valid responses were collected， including 340 from trainees and 80 from mentor pharmacists. Before training， only 30.29% of trainees were engaged in clinical pharmacy-related work， whereas this proportion increased to 73.24% after training. Most mentor pharmacists had extensive experience in clinical pharmacy （76.25% with ≥5 years of experience） and mentoring （78.75% with ≥3 teaching sessions）. Totally 65.59% of trainees and 55.00% of mentor pharmacists believed that blended training yielded the best learning outcomes. Over 80.00% of both trainees and mentor pharmacists considered the overall training duration， theoretical study time， and practical training time to be reasonable. More than 95.00% of trainees and mentor pharmacists agreed that the homework and assessment schemes were appropriate. Trainees rated the relevance of training content to their actual work highly （with an average relevance score ＞4.5）， though they perceived the chronic disease medication therapy management module as significantly more challenging than the prescription review and evaluation module and the home-based pharmaceutical care module. The average satisfaction score of trainees and mentor pharmacists with the training effectiveness of each project was above 4 points， indicating a high overall satisfaction. Inadequate provision of teaching resources was unanimously recognized by trainees and mentor pharmacists as the key area requiring improvement. CONCLUSIONS The standardized on-the-job training program for community clinical pharmacists in Shanghai has contributed to improving pharmaceutical services in community healthcare settings. However， ongoing improvements must concentrate on content design， resource development， and faculty cultivation.

The purpose of this study was to investigate the anxiety-like behaviors, circadian rhythms and sleep, and to elucidate the possible underlying mechanisms of the abnormal sleep behavior in Shank3 gene knockout (Shank3-KO) mice. The anxiety-like behaviors were detected by elevated plus-maze (EPM) test, open field test (OFT) and tail suspension test (TST). The circadian rhythms were detected by running wheel test. The electroencephalogram (EEG)/electromyogram (EMG) recordings were performed synchronically by polysomnograph. The distribution of SHANK3 in anterior cingulate cortex (ACC), paraventricular thalamus (PVT), nucleus accumbens (NAc), basolateral amygdala (BLA) and hippocampal CA2 region in wild type (WT) mice was detected by immunofluorescence assay. The protein expression of c-Fos in PVT, ACC and NAc was also detected by immunofluorescence assay during light cycle. The colocalization of c-Fos and vesicular glutamate transporter 2 (Vglut2, a marker for glutamatergic neurons) in the PVT was detected by immunofluorescence double labeling experiment. The results of EPM test showed that, compared with the WT mice, the Shank3-KO mice showed less time in open arms and less number of open arm entries. The results of OFT showed that the Shank3-KO mice showed less time in central area and less number of central area entries. The immobility time of Shank3-KO mice was increased in the TST. The results of running wheel rhythm test showed that the phase shift time of Shank3-KO mice in the continuous dark period was increased. The results of EEG/EMG recording showed that, compared with the WT mice, the duration of wakefulness in Shank3-KO mice was increased and the duration of non-rapid eye movement (NREM) sleep was decreased during light phase; The bout number of wakefulness was increased, the bout number of NREM sleep was decreased, NREM-wake transitions were increased, and wake-NREM transitions were decreased during light phase. SHANK3 was expressed in ACC, PVT, NAc and BLA in the WT mice. The expression of c-Fos in the PVT of Shank3-KO mice was up-regulated 2 h after entering the light phase, and majority of c-Fos was co-localized with Vglut2. These results suggest that the anxiety level of Shank3-KO mice is increased, the regulation of the internal rhythms is decreased, and the bout number of wakefulness is increased during light phase. The glutamatergic neurons in PVT may be involved in the regulation of abnormal sleep behavior in Shank3-KO mice during the light phase.
Animals ; Mice, Knockout ; Mice ; Neurons/metabolism* ; Nerve Tissue Proteins/physiology* ; Male ; Midline Thalamic Nuclei/cytology* ; Circadian Rhythm/physiology* ; Sleep/physiology* ; Anxiety/physiopathology* ; Proto-Oncogene Proteins c-fos/metabolism* ; Vesicular Glutamate Transport Protein 2/metabolism* ; Mice, Inbred C57BL ; Microfilament Proteins

OBJECTIVE: The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC). METHODS: Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety. RESULTS: A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group (［85.46±10.12］ and ［18.20±4.27］ (P<0.05). However, there was no significant difference in serum testosterone (［0.60±0.24］ nmol/L vs ［1.09±2.10］ nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score (［97.95±7.54］ vs ［80.33±8.58］), renal-yang deficiency syndrome score (［14.64±5.15］ vs ［24.94±8.75］) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( ［0.73±1.01］ nmol/L vs ［0.59±0.25］ nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups. CONCLUSION Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Treatment Outcome ; Testosterone

OBJECTIVE: To elucidate the modulation mechanism of Suanzaoren Decoction (SZRD) on basolateral amygdala (BLA) neuronal activity to alleviate chronic restraint stress (CRS)-related behavioral deficits. METHODS: The male C57BL/6J mice were assigned to 4 groups using the complete randomization method, including control (CON, n=19), CRS (n=19), SZRD (n=21), and fluoxetine (Flu, n=22) groups. Mice were restrained for 6 h per day, over a 21-d period to establish CRS models. The CON group remained in their cages without food or water during the 6-h matching period. SZRD and Flu groups received intragastric administration of SZRD (4.68 g/kg) and Flu (20 mg/kg) daily, respectively, 30 min before restraint for 21 consecutive days. The therapeutic effects of SZRD were evaluated using behavioral tests including the tail suspension test, elevated plus maze test, and forced swimming test. The cellular Fletcher B. Judson murine osteosarcoma proto-oncogene (c-Fos) expression in the BLA was measured using immunofluorescence, while action potential (AP) firing and synaptic transmission in BLA pyramidal neurons were evaluated using whole-cell patch-clamp recordings. RESULTS: SZRD administration significantly increased time spent in the open arms and open-arm entries while reducing immobility time (P<0.05 or P<0.01). It downregulated CRS-induced c-Fos expression and AP firing of pyramidal neurons in the BLA (P<0.01). Additionally, SZRD selectively attenuated excitatory (P<0.01), but not inhibitory, synaptic transmission onto BLA pyramidal neurons. CONCLUSION SZRD alleviated CRS-induced anxiety- and depression-like behaviors in mice by modulating the excitability and synaptic transmission of BLA pyramidal neurons.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Depression/complications* ; Pyramidal Cells/pathology* ; Male ; Mice, Inbred C57BL ; Basolateral Nuclear Complex/pathology* ; Restraint, Physical ; Anxiety/complications* ; Behavior, Animal/drug effects* ; Stress, Psychological/physiopathology* ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Action Potentials/drug effects* ; Synaptic Transmission/drug effects*

Hepatocellular carcinoma(HCC)is a serious neoplastic disease with increasing incidence and mortality,accounting for 90%of all liver cancers.Hepatitis viruses are the major causative agents in the development of HCC.Hepatitis A virus(HAV)primarily causes acute infections,which is associated with HCC to a certain extent,as shown by clinicopathological studies.Chronic hepatitis B virus(HBV)or hepatitis C virus(HCV)infections lead to persistent liver inflammation and cirrhosis,disrupt multiple pathways associated with cellular apoptosis and proliferation,and are the most common viral precursors of HCC.Mutations in the HBV X protein(HBx)gene are closely associated with the incidence of HCC,while the expression of HCV core proteins contributes to hepatocellular lipid accumulation,thereby promoting tumorigenesis.In the clinical setting,hepatitis D virus(HDV)frequently co-infects with HBV,increasing the risk of chronic hepatitis.Hepatitis E virus(HEV)usually causes acute infections.However,chronic infections of HEV have been increasing recently,particularly in immuno-compromised patients and organ transplant recipients,which may increase the risk of progression to cirrhosis and the occurrence of HCC.Early detection,effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer,while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies.This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.

Objective To evaluate the surgical treatments of refractory sclerosing peritonitis related peritoneal dialysis.Methods Clinical data of 15 patients with refractory sclerosing peritonitis related to peritoneal dialysis treated in the General Surgery Department of the 900th Hospital of the Joint Logistics Support Force of the People's Liberation Army from June 30,2014 to May 30,2018.Among them,5 cases underwent"open abdomen peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",4 cases underwent"laparoscopic peritoneal catheter removal+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter",3 cases underwent"laparoscopic peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",2 cases underwent"open abdomen peritoneal dialysis catheter removal+abdominal infection flushing and drainage with catheter",and 1 case underwent"laparoscopic examination combined with laparotomy exploration and removal of lower abdominal catheter+intestinal adhesiolysis+abdominal infection flushing and drainage with catheter".Age,gender,clinical symptoms,abdominal CT examination,peripheral blood routine,blood biochemistry,blood C-reactive protein(CRP),white blood cells,biochemistry,and aetiology of peritoneal dialysis fluid were collected and followed up,and the therapeutic effect was evaluated.Results 15 patients were transferred to the Department of Surgery after ineffective treatment in the Department of Internal Medicine.Preoperatively(after 5 days of antibiotic treatment)compared to before antibiotic treatment,there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Laparoscopic exploration or laparotomy exploration was performed,during which the peritoneal dialysis catheter was removed and the abdominal infection focus was cleared.A pelvic cavity washout drainage tube was left in place postoperatively.Fourteen patients had a good recovery after surgery,with effective control of peritonitis symptoms and no complications such as intestinal obstruction or enterocutaneous fistula.After the removal of the peritoneal dialysis catheter,all patients switched to hemodialysis.A comparison of inflammatory markers before and after surgery showed a significant decrease after surgery.Three days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there were no significant changes in blood WBC,blood NEUT％,CRP,and peritoneal fluid WBC(P＞0.05).Seven days postoperatively compared to before surgery(after 5 days of antibiotic treatment),there was a significant decrease in blood WBC[(7.43±2.65)× 109/L VS(10.17±5.24)× 109/L],blood NEUT％[(88.23±9.02)％VS(85.07±11.57)％],and CRP[(152.88±113.01)mg/L VS(114.49±92.97)mg/L](P＜0.05);the peritoneal fluid WBC at 7 days postoperatively showed no significant change compared to before surgery(after 5 days of antibiotic treatment)(P＞0.05).The cases were followed up for at least 22 months,and 13 patients did not experience peritonitis or intestinal obstruction again.One patient died 39 days after surgery due to multiple organ failure,and one patient died from other causes after a 2-year follow-up.Conclusion For refractory sclerosing peritonitis related peritoneal dialysis that is ineffective in medical conservative treatment,On the basis of reasonable and effective antibiotics to control infection,surgical intervention should be actively carried out and surgical methods such as surgery should be used to control the progress of peritonitis,reduce mortality and improve the cure rate.