Objective:To investigate the clinical characteristics and treatment mode changes of chronic pancreatitis (CP).Methods:The retrospective and descriptive study was conducted. The clinical data of 805 patients with CP who were admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2022 were collected. There were 575 males and 230 females, aged 52(range, 10-87)years. Observation indicators: (1)demographic characteristics; (2)distribution of admission departments, hospitalization and treatment status. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distri-bution were represented as M(range). Count data were expressed as absolute numbers and percentages. The chi-square goodness-of-fit test was used for consistent between expected frequency and empirical distribution. Results:(1)Demographic characteristics. Of the 805 patients, there were 435 cases and 370 cases diagnosed as CP according to the primary and secondary diagnostic criteria, respec-tively, and the age of initial presentation of 805 patients was 52(range, 10-87)years. Among male and female patients, there was 1 and 0 case in the age group of 0-10 years, there were 16 and 14 cases in 11-20 years, 45 and 26 cases in 21-30 years, 82 and 30 cases in 31-40 years, 122 and 39 cases in 41-50 years, 157 and 51 cases in 51-60 years, 119 and 46 cases in 61-70 years, 31 and 21 cases in 71-80 years, 2 and 3 cases in 81-90 years, respectively. Patients aged 0-14, 15-34, 35-64, and ≥65 years were 0, 6, 28, and 9 for 2013, 1, 21, 34, and 10 for 2014, 1, 8, 38, and 7 for 2015, 0, 7, 52, and 10 for 2016, 0, 11, 35 and 9 for 2017, 1, 15, 72 and 23 for 2018, 0, 9, 55 and 11 for 2019, 2, 19, 58 and 16 for 2020, 0,20, 79 and 18 for 2021, 0, 25, 73 and 22 for 2022, respectively. Of the 805 patients, cases from Shaanxi Province, Gansu Province and other regions were 702, 48 and 55, respectively. There are 802 Han and 3 Hui patients, respectively, and the married, unmarried, divorced, and widowed patients were 732, 64, 7, and 2, respectively. Cases with blood type information was 682, with the distribution of blood types as 26.10%(178/682) of type A, 34.46%(235/682)of type B, 9.97%(68/682) of type AB, 29.47%(201/682)of type O, showing no significant difference compared to the distribu-tion of blood types in population of Shaanxi Province in 2022 (28.43% of type A, 30.50% of type B, 9.83% of type AB, and 30.50% of type O) ( χ2=0.50, P>0.05). (2)Distribution of departments, hospita-lization, and treatment. Of the 805 patients, cases admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments (Department of Geriatric Surgery, Infectious Diseases and General Surgery) were 594, 121 and 90, respectively. Cases of the number of hospitalizations in the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 771, 121 and 94, respectively. One patient might have been admitted for multiple times. The duration of hospital of stay of 805 patients was 11(rang, 1-67)days. The duration of hospital stay of patients admitted to the Department of Hepatobiliary Surgery, Department of Gastroenterology and other departments were 16(range, 2-48)days, 11(range, 5-19)days and 24(range, 12-35)days for 2013, 18(range, 2-63)days, 10(range, 3-29)days and 14(range, 7-30)days for 2014, 9(range, 1-35)days, 11(range, 2-16)days and 10(range, 5-33)days for 2015, 10(range, 1-55)days, 9(range, 4-16)days and 16(range, 4-27)days for 2016, 9(range, 2-38)days, 10(range, 4-20)days and 11(range, 5-27)days for 2017, 12(range, 3-46)days, 11(range, 2-26)days and 13(range, 7-27)days for 2018, 11(range, 1-33)days, 9(range, 3-23)days and 14(range, 4-17)days for 2019, 11(range, 1-67)days, 7(range, 1-23)days, and 16(range, 4-27)days for 2020, 10(range, 1-35)days, 8(range, 1-32)days and 14(range, 1-29)days for 2021, 9(range, 1-42)days, 12(range, 3-17)days and 11(range, 1-22)days for 2022. Of the 805 patients, cases receiving treatment as surgical treatment, pancreas extracorporeal shock wave lithotripsy (P-ESWL), endoscopic treatment and other treatments were 258, 117, 194 and 236, respectively. A total of 260 surgeries were performed on 258 patients receiving surgical treatment, and there were 236 cases receiving surgical treatment as the first choice, and 22 cases undergoing surgery after failed of other treatments. The surgical procedures included pancreaticoduodenectomy in 79 cases, distal pancreatectomy (with or without splenectomy, Peustow procedure) in 35 cases, partial pancreatectomy with pancreatic duct incision and stone removal and pancreaticojejunostomy in 77 cases, simple pancreatic duct incision and pancreaticojejunostomy in 58 cases, internal drainage for pancreatic pseudocysts in 4 cases, and drainage for removal of pancreatic necrotic tissue in 7 cases. There were 58 patients with post-operative complications, including 9 cases of bleeding, 19 cases of infection, 2 cases of gastric paresis, 21 cases pancreatic fistula, and 7 cases of intestinal leakage. Cases with postoperative complications were recovered and discharged after symptomatic treatment. Of the 117 patients receiving P-ESWL, the times of treatment per patient was 1.3±0.7, and a total of 154 times of P-ESWL were performed. There were 89 patients receiving one time of P-ESWL, and 28 patients receiving ≥2 times of P-ESWL. Of the 194 patients receiving endoscopic treatment, the times of treatment per patient was 1.2±0.6, and a total of 238 times of endoscopic treatment were performed. There were 103 cases receiving stent placement, 43 cases receiving nasopancreatic/nasobiliary drainage, 7 cases receiving pancreatic duct balloon dilation, 71 cases receiving pancreatic stone removal, and 58 cases receiving duodenal papilla sphincterotomy. There were 168 patients receiving one time of endoscopic treatment, and 26 patients receiving ≥2 times of endoscopic treatment.There was no postoperative complica-tions reported. Conclusions:The proportion of males in CP patients is relatively high, and the proportion gradually increases with age of 51-60 years. There is no significant difference in the distribution of blood types among CP patients and the population of Shaanxi Province. The proportion of minimally invasive treatment (extracorporeal shock wave lithotripsy and endoscopic therapy) in CP treatment is on the rise, and the duration of hospital stay for patients is on the decline.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

Objective:To evaluate safety and efficacy of B-type suture method ileostomy.Methods:Clinical data from 204 patients undergoing laparoscopic low anterior resection combined with protective ileostomy was analysed. Patients were divided into B-type suture ileostomy group ( n=67) and traditional ileostomy group ( n=137). Results:compared with traditional ileostomy group, B-type suture ileostomy group showed statistically significant differences in total operation time [(164±26) min vs. (172±24) min, t=2.229, P=0.027], ileostomy time [(12.7±2.3) min vs. (14.8±2.2) min, t=-6.565, P<0.001], blood loss [(57±20) ml vs. (69±31) ml, t=-2.797, P=0.006], postoperative hospital stay [(10.2±1.9) d vs. (11.8±2.3) d, t=-4.851, P<0.001], specimen incision infection rate (0 vs. 5.1%, P=0.047), postoperative body pain [82 (79-84) vs. 78 (76-80), Z=-5.805, P<0.001], and ileostomy incorporation time [(46±11) min vs. (51±12) min, t=-2.540, P=0.012]. Conclusion:B-type suture ileostomy for prophylactic ileostomy in laparoscopic low anterior resection for rectal cancer is safe and feasible.

Overtraining is a condition characterized by various functional disorders or pathological states caused by continuous fatigue, which occurs after a persisting imbalance between training-related load and physical function and recovery. Generally speaking, it’s a state of imbalance between training and recovery, exercise and exercise performance, and stress and stress tolerance. Overtraining can cause various phenotypic changes or pathological remodeling, such as decreased skeletal muscle strength and exhaustive exercise endurance, skeletal muscle fatigue damage and dysfunction, skeletal muscle atrophy and loss, skeletal muscle glycogen depletion, skeletal muscle soreness and stiffness, skeletal muscle glucose intolerance, inattention, memory decline, anxiety, depression, abnormal emotions and behaviors, sleep disorders, cognitive function impairment, poor appetite, weight loss, liver/heart fat deposition, compensatory increase of liver/heart insulin signaling and glycogen storage, cardiac pathological hypertrophy, exercise-induced arrhythmias, myocardial fibrosis, ectopic and visceral fat deposition, and increased risk of injury. Unfortunately, its underlying mechanism is largely unclear. Recently, the enrichment of molecular and cellular signal pathway theory offers us a new explanatory paradigm for revealing its internal mechanisms. Based on the traditional explanation mechanisms and molecular and cellular signal pathway theory, we thoroughly analyzed the key mechanisms of health damage caused by overtraining from the perspective of oxidative stress, mitochondrial quality control disorder, inflammatory response, endoplasmic reticulum stress, cell apoptosis, and so forth. Specifically, overtraining-induced excessive reactive oxygen species (ROS) leads to serious oxidative stress damage in organisms at least via depressing Kelch like ECH associated protein 1(Keap1)/nuclear factor erythroid-2-related factor (Nrf2)/antioxidant response element (ARE) antioxidant pathway and activating p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Overtraining induces mitochondrial quality control disorder and mitochondrial dysfunction, and thus triggers health impairment through inhibiting mitochondrial biogenesis and fusion, stimulating mitochondrial fission, and over-activating autophagy/mitophagy. Overtraining can also produce muscle, skeletal and joint trauma, then circulating monocytes are abundantly activated by injury-related cytokines, and in turn generate large quantities of proinflammatory IL-1β, IL-6, TNF‑α, causing systemic inflammation and inflammatory health injury. Overtraining induces excessive pathological endoplasmic reticulum stress (ERS) and severe health damage via PERK-eIF2α, IRE1α-XBP1 and ATF6 pathways which activated by proinflammatory signals. Overtraining also induces excessive apoptosis and harmful health consequences via Bax/Bcl2-Caspase 3-mediated mitoptosis which activated by oxidative stress and inflammation or even CHOP and Caspase 12-dependent ERS apoptosis. Nonetheless, it should be importantly emphasized that oxidative stress and inflammation are the central and pre-emptive mechanisms of overtraining and its health damage. Although the efficient strategies for preventing and controlling overtraining are scientifically and reasonably arranging and planning training intensity, training volume, and recovery period, as well as accurately assessing and monitoring physical function status in the early stage, yet various anti-inflammatory, anti-oxidant, anti-apoptotic, or anti-aging drugs such as curcumin, astaxanthin, oligomeric proanthocyanidins, silibinin, hibiscus sabdariffa, dasatinib, quercetin, hydroxytyrosol, complex probiotics, astragalus polysaccharides, semaglutide and fasudil also have an irreplaceable positive effect on preventing overtraining and its relevant health damage via depressing oxidative stress, mitochondrial quality control disorder, proinflammatory signals, endoplasmic reticulum stress, apoptosis and so on. We hope that this review can help us further grasp the features, mechanisms and regularity of overtraining, and provide an important reference for athletes and sports fan to conduct scientific training, improve training effectiveness, extend exercise lifespan, and promote physical and mental health.

Tablets represent the most widely used oral solid dosage form in the pharmaceutical industry. Puerarin monohydrate (PUEM), a solid form of the natural antihypertensive drug puerarin, is commercially available. However, the low solubility of PUEM poses a significant challenge for the development of its tablet dosage form. In this study, we successfully prepared the sodium chelates of puerarin (PUE-Na·7H₂O) using reactive crystallization techniques. The crystal structure of PUE-Na·7H₂O was analyzed using single crystal technology, which revealed the structural characteristics of its metal chelate. Our thermodynamic studies demonstrated that the formation of PUE-Na·7H₂O involved the simultaneous deprotonation of PUE and the chelation of PUE^- and Na⁺. This reaction process was spontaneous and exothermic (ΔG < 0, ΔH < 0), and reducing the temperature facilitated the formation of the chelate. Nucleation kinetics studies revealed that chelate molecules were more likely to nucleate and crystallize under low temperature, high concentration, and high rotational speed conditions. Compared to commercially available PUEM, PUE-Na·7H₂O showed significantly improved water solubility, with a 33.5-fold increase in solubility and a 37.6-fold decrease in intrinsic dissolution rate. Our study identified drug-sodium chelation as an effective means for improving drug solubility and elucidated the mechanisms governing its formation kinetics and thermodynamics. These findings could provide new solutions for related product development and tremendous commercial opportunities.

Pharmaceutical excipients, as an indispensable part of drug preparation, play crucial roles as drug carriers, improving drug release, ensuring drug stability, and enhancing patient compliance. Traditional Chinese Medicine (TCM) boasts a rich developmental history. With the modernization of technology, the deep integration of pharmacy, chemistry, and materials science has provided broader opportunities for innovative research in TCM. Simultaneously, the demand for high-quality excipients has become increasingly critical.This paper aims to review current research and applications of excipients in TCM preparations, including pre-mixed and co-processed excipients, modified excipients, and the unification of drugs and excipients, such as flavoring agents, fillers, penetration enhancers, and delivery systems. A meticulous synthesis and analysis of existing research aims to provide a reference for selecting excipients in TCM preparations, stimulate innovation in excipient development for TCM, and advocate for the development of personalized excipients.

Taking the Ligustrum lucidum extract as an example, this study investigated the influence of external mechanical forces under different processing conditions on the crystallographic solid form and the key parameter of drug dissolution rate, so as to provide guidance for the preparation and quality control of traditional Chinese medicine preparations. Under different pulverization and tableting conditions, the change of crystallographic solid form of L. lucidum extract was observed by polarizing light microscope. Meanwhile, the effect of this change on the dissolution rate was investigated, and the mathematical relationship between crystal content and dissolution rate was analyzed. The results showed that the process of ball milling and tableting had a significant impact on the crystallographic solid form of L. lucidum extract. The amorphous extract displayed crystal transformation, which induced a significant decline in dissolution rate. Further studies revealed that there was a negative linear relationship between crystal content and dissolution rate. The results of this study indicated that the crystallographic solid form transformation of traditional Chinese medicine extracts might occur during the preparation process, which may cause potential risks to the quality of traditional Chinese medicine preparations. It is suggested that we should pay attention to and strengthen the investigation of the crystallographic solid form during the preparation process, so as to guarantee the safety, effectiveness, and quality controllability of traditional Chinese medicine preparations.

In recent years, bio-metal organic frameworks (Bio-MOFs) synthesized with biocompatible ligands have been widely investigated as a potential drug delivery carrier due to their large specific surface area and porosity, rich host-guest intermolecular interactions, and good biocompatibility.In this review, we summarized the design methods of Bio-MOFs including structural and toxic factors, as well as a variety of drug loading methods including click chemistry, with particular focus on recent research advances in Bio-MOFs for pulmonary drug delivery systems, improving pharmaceutical properties of drugs, sustained and controlled drug release, stimulation response and targeted drug delivery systems.Finally, we summarized the bottlenecks that constrain the development of Bio-MOFs in clinical studies of actual pharmaceutical formulations and their future directions for approved formulations, aiming to provide some theoretical reference for promoting the application of Bio-MOFs in drug delivery systems.

In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

Cocrystal separation technology is a technology that utilizes coformers to selectively form cocrystals with target compounds and separate them from mixed systems. Our study used puerarin (PUE), daidzein (DDZ), and genistein (GEN) as model drugs, which have similar structures and are the main isoflavones in Pueraria lobata root. The separation and purification processes in the modern traditional Chinese medicine (TCM) of these three components use conventional column chromatography, recrystallization, and other technologies, which have the issues of lengthy separation cycles, high solvent consumption, and inefficient preparation. Different with existing separation technology, our team used the early-found cocrystal separation method to design a step-by-step extraction and separation experiment of GEN-PUE-DDZ ternary mixture. Caffeine and L-proline were added to the mixed system in turn, GEN-caffeine cocrystal and PUE-proline cocrystal were prepared by suspension method. The cocrystals precipitated out of the solution. The purities of the GEN-caffeine cocrystal and the PUE-proline cocrystal could achieve 93% (the purity of GEN) and 99% (the purity of PUE). Besides, the purity of DDZ could also be increased by 6.76 times. This study proposed a simple operating, low cost and wide application range separation method different from the traditional separation method and realized the separation of structurally similar chemical components in TCM, laying a foundation for the application of cocrystal technology in the separation and refining of TCM.