The occurrence of diabetes mellitus （DM） is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver，fat，skeletal muscle，islets， and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response，improving insulin resistance，and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing，heat-clearing， and detoxicating medicinal，which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore，by summarizing the mechanisms between macrophage activation，polarization， and insulin resistance in various tissues，this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio，providing references for the future treatment of DM and its related complications with traditional Chinese medicine.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the clinical effect of ultrasound induction combined with acupunc-ture points and polyethylene glycol 4000 powder for treating constipation in elderly patients with hip fracture. Methods A randomized parallel controlled method was adopted.A total of 100 inpatients meeting the inclu-sion criteria were divided into the control group and treatment group.Fifty cases in the control group were given polyethylene glycol 4000 powder,10 g/d,taking at a draught in 1 h after lunch.Fifty cases in the treat-ment group adopted the ultrasound induction combined with Shenque acupoint and Guanyuan acupoint,which was implemented at 1 h after lunch every day,once a day,30 min each time,and the intensity was appropriate for the patients to tolerate.The two groups were continuously treated for 1 week.The clinical symptoms be-fore and after treatment in the two groups were observed.The constipation score,quality of life score,treat-ment efficacy and safety were compared between before and after treatment.Results There were 3 dropout cases in the control group and 47 cases were finally included.Among them,14 cases were excellently effective,20 cases were effective,13 cases were ineffective,and the total effective rate was 72.34％;there were 2 dropout cases in the treatment group and 48 cases were finally included.Among them,15 cases were excellently effec-tive,18 cases were effective,15 cases were ineffective,and the total effective rate was 68.75％;the total effec-tive rate had no statistical difference between the two groups (P>0.05).The effect onset time of the treat-ment group was earlier than that of the control group with statistical difference (P<0.05).The abdominal symptom dimension and total score in the constipation scores after treatment in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05).After treat-ment,the physiological,satisfaction dimension scores and total score in life quality score in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05). During the test process,2 cases in the control group had adverse drug reactions,which manifested by mild di-arrhea at the end of the treatment course,and no adverse reactions were found in the treatment group.Conclu-sion The ultrasound induction combined with acupuncture points for treating constipation in elderly patients with hip fracture has equivalence with polyethylene glycol 4000 powder,moreover which has the advantages in the aspects of effect onset time and improvement of abdominal symptoms.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.