Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

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.

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.

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 investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.

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.