Xanthine oxidase (XO) is an important therapeutic target for the treatment of hyperuricemia and gout. Based on the previously identified potent XO inhibitor 1, seventeen oxadiazoles and their ring-opening analogues were designed and synthesized via the bioisostere replacement strategy. Among them, compounds 2l, 2n, and 3b showed obvious XO inhibitory activity at the concentration of 10 μmol·L^-1, and compound 3b exhibited an IC₅₀ value of 1.45 μmol·L^-1.

In this paper， by referring to ancient and modern literature， the textual research of Kochiae Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， taste and efficacy， harvesting time， processing and compatibility taboo， so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation， it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic， and has been used as the official name throughout history. It is also known by other names such as Dimai， Dikui， and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia， which is consistent throughout history. In the Han dynasty， it was recorded that Kochiae Fructus was produced in Jingzhou（Hubei province）， while modern literature records its distribution throughout the country， so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn， and the quality is best when it is full， gray green in color， and no impurities. There are two processing methods for its origin：from the Southern and Northern dynasties to the Ming dynasty， it was dried in the shade， and after the founding of the People's Republic of China， it was dried in the sun. There are few records about the processing of Kochiae Fructus， and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar， and the leaves are taken in April and May， processing in the place of origin is shade drying， the processing methods include burning ash and frying frost， pounding juice and wine soaking. For internal use， it is mostly decocted or mashed， while for external use， it is mostly washed with decoction or taken in a soup bath. Throughout history， it has been recorded that Kochiae Fructus is bitter and cold， and is mainly used for treating bladder fever. After the founding of the People's Republic of China， most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia， it has been recorded that Kochiae Fructus has a pungent and bitter taste， and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness， dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history， it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times， it has been used to regulate the liver， spleen and large intestine meridians， with functions such as clearing heat and detoxifying， and diuresis. Based on the textual research， it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus， and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements， the raw products is taken into medicine.

In this paper， by referring to ancient and modern literature， the textual research of Cnidii Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， nature and flavour， efficacy， harvesting and processing， compatibility taboo and others， so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research， it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic， the materia medica of all dynasties was named Shechuangzi， and there are also aliases such as Shesu， Shemi， and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri， and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty， the origin of Cnidii Fructus was Zibo， Shandong province. During the Five dynasties， it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province， the Song dynasty added Shangqiu in Henan province， and it was considered that Yangzhou， Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China， the origin is clearly distributed throughout the country. For its quality evaluation， generally full grain， gray yellow color， strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month， and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products， mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past， there were also stir-frying with honey， stir-frying with salt and rice wine， immersing and steaming with rice wine and other methods. In recent times， it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter， Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm， acted on the kidney meridian， and had small toxicity. After the founding of the People's Republic of China， most of the literature classified it as a medicine to attack poison， kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness， destroying parasites and elieving itching， warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research， it is suggested that when developing the famous classical formulas containing Cnidii Fructus， the source shall be the dried ripe fruit of C. monnieri， and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas， the raw products can be taken into medicine.

In this paper， by consulting the ancient and modern literature， the name， origin， quality evaluation， harvesting and processing， and others of the original animal and medicinal materials of Moschus were systematically sorted out and verified， in order to provide the basis for the development and utilization of the famous classical formulas containing Moschus. According to the textual research， musk deer was first recorded in Shanhaijing. Shennong Bencaojing was recorded as Moschus and all generations were used as the correct name， but there were also aliases such as Shefu， Xiangzhang and Xiangqizi. In ancient times， Moschus berezovskii， M. sifanicus and M. moschiferus were the main sources of Moschus， and the quality of Moschus produced in northwest China was better than that produced in the Yangtze River basin. In modern times， Moschus of M. moschiferus produced in northeast China， M. sifanicus produced in Gansu， Sichuan and other places， and M. berezovskii produced in Ningxia， Shaanxi and other places are regarded as genuine. In ancient times， gunshots， lassoes， arrow shots and other methods were generally used to hunt live musk deer， and the sachets were immediately cut off. Those with high quality were called Xiangshanhuo， and dried in the shade after harvesting， which was known as Maoke Shexiang. Cut open the sachet， remove the shell and dry preservation， commonly known as Moschus kernel. In modern times， the method of taking Moschus from the living body of cultured musk deer is adopted， that is， Moschus kernel is directly taken from its sachet， dried in the shade or dried in a closed dryer. This method realizes the sustainable utilization of Chinese herbal medicine resources， but attention should be paid to the frequency and quality of Moschus. The harvesting time is mostly after the autumnal equinox every year， and before the next summer， it is better to gather sachet in winter. In recent times， it is believed that the shell Moschus is dry， full， thin， elastic， loose inside， many particles， strong and persistent aroma for the best， while the Moschus kernel is particle purple-black， powder yellow-brown， soft and oily texture， strong and persistent aroma for the best. The ancient processing method of Moschus was extracting kernels from the shell. After removing impurities， it is ground and used as medicine. Because its composition is not suitable for heating， the processing method is most common in preparations such as grinding into powder and putting into pills or powders， which has the effect of opening up the orifices and refreshing the mind， and it has continued to this day. Based on the research conclusions， it is suggested that the development of famous classical formulas containing Moschus， M. sifanicus， M. moschiferus and M. berezovskii should be used as the origins. According to the processing requirements specified in the original formula， it should be processed and used as medicine， while those without processing requirements should be used as raw products.

By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

By consulting the ancient and modern literature， the textual research of Pharbitidis Semen has been conducted to clarify the name， origin， distribution of production areas， quality specification， harvesting， processing and so on， so as to provide reference for the development and utilization of the relevant famous classical formulas. Through textual research， it can be seen that Pharbitidis Semen was first published in Mingyi Bielu（《名医别录》）， and all dynasties have taken Qianniuzi as the correct name. Based on the original research， the main source of Pharbitidis Semen used in previous dynasties is the dried mature seeds of Pharbitis nil， which is consistent in ancient and modern times. The white Pharbitidis Semen appearing in Compendium of Materia Medica（《本草纲目》） from Ming dynasty is similar to the present P. purpurea. It is produced all over the country， and the quality is better if the particles are full and free of impurities. In ancient times， the harvesting time was mostly in the September. Now it is autumn. The fruits are ripe and harvested， dried to remove impurities for standby. In ancient times， the processing methods of Pharbitidis Semen were mainly wine steaming， steaming and frying until half cooked and grinding the head and end. In modern times， they have been simplified to stir-frying method. The nature， taste， meridian tropism and their effects also change supplements with the deepening of practice. Before the Ming dynasty， they were all bitter， cold and toxic. In the Ming dynasty， there appeared the characteristics of pungent， hot and small poisonous. The efficacy has evolved from controlling low Qi， curing foot edema， removing wind toxin， and facilitating urination to facilitating water and defecation， eliminating phlegm and drinking， and eliminating accumulated insects. The main clinical contraindications are those with weak spleen and kidney， those with weak spleen and stomach， pregnant women， and should not be used with croton and croton cream. Based on the textual research， it is suggested that when developing the classic famous formula with Pharbitidis Semen as the main raw material in the future， it is clear that the source should be the dried mature seeds of Pharbitis nil（black product is its black-brown seeds， white product is its beige seeds）. The processing requirements indicated in the original formula are all processed according to the requirements， and the raw product is recommended to be used as medicine if not specified.

The main protease (M^pro) of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle. The covalent M^pro inhibitor nirmatrelvir (in combination with ritonavir, a pharmacokinetic enhancer) and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use. Effective antiviral drugs are needed to fight the pandemic, while non-covalent M^pro inhibitors could be promising alternatives due to their high selectivity and favorable druggability. Numerous non-covalent M^pro inhibitors with desirable properties have been developed based on available crystal structures of M^pro. In this article, we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^pro inhibitors, followed by a general overview and critical analysis of the available information. Prospective viewpoints and insights into current strategies for the development of non-covalent M^pro inhibitors are also discussed.

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

Antiviral drug research and development is an important research direction in the current and future biomedical field. The research and development of antiviral drugs not only requires the application of new strategies and new technologies, but also requires the complementary advantages and close cooperation of project teams. Based on the latest progress in this field and the author's drug research practice, this paper summarizes the underlying logic, innovative thinking and research paradigm of antiviral medicinal chemistry.

OBJECTIVE To systematically evaluate the efficacy and safety of compound danshen preparations combined with conventional chemical drug treatment for peptic ulcer （PU）， providing evidence-based guidance for clinical treatment of PU. METHODS Related clinical randomized controlled trials were collected from CNKI， VIP， Wangfang data， CBM， PubMed， Embase and Web of Science from their establishment date to September 30， 2023. The qualities of included literature were evaluated by Cochrane Systematically Evaluator Manual 5.1.0. Meta-analysis， sensitivity analysis and publication bias analysis were conducted with RevMan 5.3 software. RESULTS Totally 26 pieces of literature were included with total of 2 451 cases， including 1 243 cases in trial group （compound danshen preparations+conventional chemical drug treatment） and 1 208 cases in the control group （conventional chemical drug treatment）. In terms of effectiveness， trial group had significant advantages in ulcer healing rate [OR＝4.66， 95%CI （3.53， 6.15）， P＜0.000 01]， HP eradication rate [OR＝1.90， 95%CI （1.12， 3.22）， P＝0.02]，and pain relief rate [OR＝3.91， 95%CI （2.31， 6.61）， P＜0.000 01] than control group， while ulcer recurrence rate [OR＝0.22， 95%CI （0.15， 0.32）， P＜0.000 01] and serum levels of pepsinogen （PG）Ⅰ [SMD＝－1.92， 95%CI （－2.25， －1.58）， P＜0.000 01]， PGⅡ [SMD＝－3.88， 95%CI （－4.35， －3.41）， P＜0.000 01] and G-17 [SMD＝－3.44， 95%CI （－3.87， －3.00）， P＜0.000 01] were significantly lower than control group. In terms of safety， the main adverse reactions were abdominal discomfort， headache， dizziness， dry mouth， facial flushing， etc. There was no significant difference in the incidence of adverse reactionsbetween the two groups [OR＝1.08， 95%CI （0.75， 1.54）， P＝0.69]. Subgroup analysis of ulcer healing rate and HP eradication rate based on dosage form showed that HP eradication rate in the compound danshen pellet group was not significantly improved compared to the control group， with consistent results for the remaining outcomes. The sensitivity analysis showed that above results were stable. There was less possibility of publication bias in this study. CONCLUSIONS Compared with conventional chemical drug treatment alone， the combination of compound danshen preparations can effectively improve the clinical symptoms of PU patients with similar safety.