This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

This article systematically reviews and verifies the name， origin， production area， quality evaluation， harvesting， processing and other aspects of Cynanchi Atrati Radix et Rhizoma（CARR） by consulting relevant ancient and modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research， Baiwei has been the official name for CARR， though it also bears alternative names such as Chuncao， Popo Zhenxianbao， Longdan Baiwei. The mainstream base is the roots and rhizomes of Cynanchum atratum. Historical records indicate primary producing areas include Shandong， Anhui， Jiangsu， Shaanxi and Shanxi. Since the late Ming dynasty， varieties from Juxian， Yishui and Rizhao in Shandong have been highly regarded as authentic， commonly known as eastern Baiwei. Since modern times， its quality has been summarized as fine， slender， and straight fibrous roots， pale yellow exterior， whiter interior， and dryness with easy breakability are considered superior. The harvesting time before the Song dynasty was on the third day of the third lunar month， but after the Song dynasty， harvesting was possible in both spring and autumn. The initial processing methods of CARR in ancient times included drying in the shade， removing Lu（the little rhizomes which are on tap of roots）， and removing mustaches， modern methods involve washing and sun-drying. During the Northern and Southern dynasties， processing methods included steaming. In the Song dynasty， drying and light stir-frying were predominant， while wine washing emerged in the Ming dynasty. Modern practices primarily involve using raw， stir-frying or honey processing. Regarding the medicinal properties of CARR， both ancient and modern texts agree it has a bitter and salty taste and is non-toxic. Records prior to the Qing dynasty predominantly describe its nature as extremely cold， while mainstream herbal texts after the Qing dynasty generally characterize it as cold. Before the Ming dynasty， there were no records of its meridian tropism. It was not until the Qing dynasty that it was recorded in the lung meridian. Modern records mainly refer to the stomach， liver， and kidney meridians. Throughout history， its main functions have been to clear heat， diuresis， nourish Yin， and replenish essence， primarily treating Yin deficiency and fever syndrome. Based on the research results， it is suggested that when developing famous classical formulas containing CARR， the dried roots and rhizomes of C. atratum can be selected as its medicinal source. If there are no specific processing requirements， raw products can be selected as medicine. If the processing requirements are specified， corresponding processed products can be selected as medicine according to the original formula requirements.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

The structural characteristics and clinical application of embolic microspheres were summarized in this paper. According to evaluation experience and current regulatory registration evaluation requirements, registration evaluation concerns on embolic microsphere as medical device were analyzed from four aspects: administration attributes, product description, non-clinical studies and clinical evaluation, in order to provide references for the development and registration application of such products and improve the efficiency of registration application.
Microspheres ; Device Approval ; Embolization, Therapeutic/instrumentation*

Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Objective:To investigate the effects and underlying mechanisms of Stat3 knockout in donor T cells on acute gastrointestinal graft-versus-host disease (GI-aGVHD) .Methods:BALB/c mice were exposed to lethal irradiation and transplanted with bone marrow and spleen cells from BALB/c mice (syngeneic control group), C57BL/6 mice (wild-type T cell group, WT group), or C57BL/6J-Stat3 em1cyagen mice (Stat3 gene knockout T cell group, Stat3-KO group) via tail vein injection to establish the aGVHD model. The survival rate, body weight changes, and clinical scores of mice were monitored. Cytometric bead array (CBA) was used to detect the concentrations of serum cytokines. Lymphocytes were isolated from tissues for flow cytometric analysis. H&E staining was performed to observe intestinal pathological changes. FITC-dextran assay was conducted to assess intestinal permeability. Immunohistochemistry was used to evaluate the expression of Ki67 and Muc2. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was employed to analyze the gene expression levels of Olfm4, Lysozyme, and Muc2 in the small intestine. Metabolomics was conducted to detect metabolites in serum and intestinal tissues. An in vitro GI-aGVHD organoid model was established by coculturing intestinal organoids with allogeneic T cells, where the number and area of small intestinal organoids were recorded. The GVL effect was assessed using luciferase-transfected ALL cells (ALL/Luc) and bioluminescent imaging. Results:Compared with the WT group, Stat3 knockout T cells alleviated body weight loss, reduced symptoms—such as hunchback and diarrhea—in mice, improved survival rate ( P<0.05), and reduced serum interleukin (IL) -2, IL-6, interferon-γ, tumor necrosis factor-α, IL-17A, and IL-10 levels (all P<0.05), intestinal inflammatory cell infiltration ( P<0.05), and intestinal mucosal permeability. Further, Muc2 and Ki67 expression levels in the small intestine of the Stat3 knockout group were markedly increased, and Olfm4, Lysozyme, and Muc2 gene expression levels were significantly increased (all P<0.05). In vitro, the Stat3 knockout group demonstrated better organoid development than the WT group. Metabolomic analyses indicated that Stat3 knockout in T cells may affect the pathways associated with bile acid secretion and unsaturated fatty acids. ALL/Luc cells in the GVL mouse model proliferated rapidly in the TCD-BM group; however, 80% of the mice in the Stat3-KO group survived tumor-free for >100 days ( P<0.05) . Conclusion:Knocking out Stat3 in graft T cells reduces T cell damage to intestinal stem cells, thereby ultimately alleviating GI-aGVHD while maintaining a stable GVL effect.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.

Functional cure is currently recommended by guidelines as the ideal treatment goal for the prevention and treatment of chronic hepatitis B （CHB） in China and globally， and it is defined as sustained and undetectable serum HBsAg and HBV DNA， HBeAg clearance， and presence or absence of HBsAg seroconversion， accompanied by resolution of liver inflammation， histopathological improvements， and a significant reduction in the incidence rate of end-stage liver disease. HBV can integrate into the host genome and contribute to the continuous production of HBsAg， which can occur in the early stage of chronic HBV infection. In addition to the covalently closed circular DNA that is hard to be eliminated in liver tissue， HBsAg derived from HBV integration independent of viral replication may be the most important factor for the difficulty in achieving functional cure after antiviral therapy in patients with hepatitis B. This article reviews the research advances in HBV integration in recent years and discusses its impact on functional cure.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Purpose: Human epidermal growth factor receptor 2 (HER2)-low breast cancer has the potential to emerge as a distinct subtype. Several studies have compared the differences between HER2-low and HER2-0 breast cancers, but no consensus has been reached.Additionally, a biomarker to predict pathological complete response (pCR) rates in patients with HER2-low breast cancer remains to be identified. Methods: We collected data from 777 patients across three centers, stratifying them into HER2-low and HER2-0 groups. We compared differences in survival and pCR rates between the two groups and investigated potential biomarkers that could reliably predict pCR. Results: The study found that patients with HER2-0 breast cancer had higher pCR rates compared to patients with HER2-low tumors (289 patients [30.1%] vs. 475 patients [18.1%], p < 0.0001). Survival analysis showed no significant advantage for HER2-low tumors over HER2-0 breast cancers. Binary logistic analysis revealed that androgen receptor (AR) expression predicts poorer pCR rates in both the overall patient group and the HER2-0 breast cancer group (overall patients: odds ratio [OR], 0.479; 95% confidence interval [CI], 0.250–0.917; p = 0.026 and HER2-0 patients: OR, 0.267; 95% CI, 0.080–0.892; p = 0.032). In contrast, programmed death ligand 1 (PD-L1) expression was associated with more favorable pCR rates in the overall patient group (OR, 3.199; 95% CI, 1.020–10.037; p = 0.046). Conclusion There is currently insufficient evidence to classify HER2-low breast cancer as a distinct subtype. Our study revealed that AR expression, along with negative PD-L1 expression, contributes to lower pCR rates.