The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells （KGN cells） in polycystic ovarian syndrome （PCOS） and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52， 1.04， 2.08 g/（kg·d）] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum， KGN cells were divided into control group （without any treatment）， dehydroepiandrosterone （DHEA） group （treated with 50 μmol/L DHEA for 48 h）， blank serum group （treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h） and medium-concentration of Siwutang medicated serum group （treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h）. The number of autophagosomes was observed in each group， and protein expressions of pathway-related proteins [fructose-1， 6-bisphosphatase 1 （FBP1），mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）]， autophagy-related proteins [p62， microtubule-associated protein 1 light chain 3 （LC3）] and mRNA expression of FBP1 were also detected. The （transfected） cells were further divided into Siwutang group （treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA）， Siwutang+si-NC group [negative control small interfering RNA （siRNA） transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group （FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration Siwutang medicated serum for 72 h）. The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group， DHEA group exhibited an increase in the number of autophagosomes， an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR， as well as increases in protein and mRNA expressions of FBP1， and decreased protein expression of p62 （P＜0.05）. Compared to both DHEA group and blank serum group， the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes， a decrease in LC3-Ⅱ/LC3-Ⅰ， and increases in p-mTOR/mTOR， protein expression of p62， protein and mRNA expressions of FBP1 （P＜0.05）. After knocking down FBP1， compared with Siwutang+si-NC group， Siwutang+si-FBP1 group showed a significant decrease in cell viability， protein expression of p62 ， protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR， and an increase in LC3-Ⅱ/LC3-Ⅰ （P＜0.05）. CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells， thus inhibiting autophagy of KGN cells.

OBJECTIVE To investigate the effects of medicated serum of Siwutang on autophagy of ovarian granulosa cells （KGN cells） in polycystic ovarian syndrome （PCOS） and its underlying mechanism. METHODS Blank serum and different- concentration medicated serum of Siwutang were prepared by intragastric administration of normal saline and different doses of Siwutang [0.52， 1.04， 2.08 g/（kg·d）] in 3-month-old female SD rats. After screening the intervention concentration of Siwutang medicated serum， KGN cells were divided into control group （without any treatment）， dehydroepiandrosterone （DHEA） group （treated with 50 μmol/L DHEA for 48 h）， blank serum group （treated with 50 μmol/L DHEA for 48 h and with 10% blank serum for 72 h） and medium-concentration of Siwutang medicated serum group （treated with 50 μmol/L DHEA for 48 h and with 10% medium-concentration Siwutang medicated serum for 72 h）. The number of autophagosomes was observed in each group， and protein expressions of pathway-related proteins [fructose-1， 6-bisphosphatase 1 （FBP1），mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）]， autophagy-related proteins [p62， microtubule-associated protein 1 light chain 3 （LC3）] and mRNA expression of FBP1 were also detected. The （transfected） cells were further divided into Siwutang group （treated with 10% medium dose of Siwutang medicated serum for 72 h after 48 h intervention with 50 μmol/L DHEA）， Siwutang+si-NC group [negative control small interfering RNA （siRNA） transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration of Siwutang medicated serum for 72 h] and Siwutang+si-FBP1 group （FBP1 siRNA transfected cells treated with 50 μmol/L DHEA for 48 h， and then with 10% medium-concentration Siwutang medicated serum for 72 h）. The effects of knocking down FBP1 on the above-mentioned effects of Siwutang were detected. RESULTS Compared with control group， DHEA group exhibited an increase in the number of autophagosomes， an elevated LC3-Ⅱ/LC3-Ⅰ and p-mTOR/mTOR， as well as increases in protein and mRNA expressions of FBP1， and decreased protein expression of p62 （P＜0.05）. Compared to both DHEA group and blank serum group， the medium-concentration of Siwutang medicated serum group showed a decrease in the number of autophagosomes， a decrease in LC3-Ⅱ/LC3-Ⅰ， and increases in p-mTOR/mTOR， protein expression of p62， protein and mRNA expressions of FBP1 （P＜0.05）. After knocking down FBP1， compared with Siwutang+si-NC group， Siwutang+si-FBP1 group showed a significant decrease in cell viability， protein expression of p62 ， protein and mRNA expressions of FBP1 as well as p-mTOR/mTOR， and an increase in LC3-Ⅱ/LC3-Ⅰ （P＜0.05）. CONCLUSIONS Siwutang can promote the phosphorylation of mTOR protein by up- regulating the protein and mRNA expressions of FBP1 in KGN cells， thus inhibiting autophagy of KGN cells.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

ObjectiveTo observe the clinical efficacy and safety of hot ironing with Haitongpi Formula （海桐皮方， HF） in the treatment of lumbar disc herniation （LDH） of cold-dampness obstruction type. MethodsA total of 70 patients with cold-dampness obstruction type LDH were randomly divided into a treatment group and a control group， with 35 cases in each group. Both groups received three movements technique of Qinggong Spinal Manipulation （QSM） as the basis for treatment. In addition， the treatment group received hot ironing with HF， while the control group applied Diclofenac Sodium Gel externally. The treatment duration for both groups was 14 days. The clinical efficacy was compared between groups. Japanese Orthopedic Association （JOA） score， visual analog scale （VAS） for pain， pain pressure threshold （PPT） for lumbar positive response points， and traditional Chinese medicine （TCM） symptom scores were compared， on day 7， and day 14 of treatment， as well as on day 7 and day 14 of follow-up. The lumbar curvature index （LCI） was also compared before treatment and on day 14 of treatment. Adverse reactions during the study were recorded for both groups. ResultsA total of 35 patients in the treatment group and 34 patients in the control group were included for final analysis. The clinical total effective rate of the treatment group （91.43%， 32/35） was significantly higher than that of the control group （82.35%， 28/34， P＜0.05）. Both the JOA score and PPT of the two groups increased on day 7 and day 14 of treatment， and on day 7 and day 14 of follow-up. VAS scores and TCM symptom scores both decreased. The LCI of both groups increased on day 14 of treatment （P＜0.01）. Compared with the control group at the same time points， on day 14 of treatment and day 7 and day 14 of follow-up， the treatment group had higher JOA scores and PPT， and lower VAS scores and TCM symptom scores. The LCI of the treatment group increased on day 14 of treatment （P＜0.05 or P＜0.01）. One case in the control group showed mild skin allergy， with no other adverse reactions observed in either group. ConclusionBased on three movements technique of QSM， hot ironing with HF shows better clinical efficacy than external Diclofenac Sodium Gel in the treatment of cold-dampness obstruction type LDH. It can significantly reduce lumbar pain， increase pain pressure threshold， improve clinical symptoms， lumbar function， and lumbar curvature， with good safety.